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@article{fds370942,
Author = {Watson, NF and Bertisch, SM and Morin, CM and Pelayo, R and Winkelman,
JW and Zee, PC and Krystal, AD},
Title = {Do Insomnia Treatments Improve Daytime Function?},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {9},
Year = {2023},
Month = {April},
url = {http://dx.doi.org/10.3390/jcm12093089},
Abstract = {A scientific advisory panel of seven U.S. and Canadian sleep
experts performed a clinical appraisal by comparing general
medical opinion, assessed via a survey of practicing
clinicians, regarding insomnia treatment, with the available
scientific evidence. This clinical appraisal focuses on the
specific statement, "Treatments for insomnia have uniformly
been shown to significantly improve the associated daytime
impairment seen with insomnia." The advisory panel reviewed
and discussed the available body of evidence within the
published medical literature to determine what discrepancies
may exist between the currently published evidence base and
general medical opinion. The advisory panels' evaluation of
this statement was also compared with the results of a
national survey of primary care physicians, psychiatrists,
nurse practitioners, physician assistants, and sleep
specialists in the United States. Contrary to general
medical opinion, the expert advisory panel concluded that
the medical literature did not support the statement. This
gap highlights the need to educate the general medical
community regarding insomnia treatment efficacy in pursuit
of improved treatment outcomes.},
Doi = {10.3390/jcm12093089},
Key = {fds370942}
}
@article{fds370751,
Author = {Pelayo, R and Bertisch, SM and Morin, CM and Winkelman, JW and Zee, PC and Krystal, AD},
Title = {Should Trazodone Be First-Line Therapy for Insomnia? A
Clinical Suitability Appraisal.},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {8},
Year = {2023},
Month = {April},
url = {http://dx.doi.org/10.3390/jcm12082933},
Abstract = {Trazodone is one of the most commonly used prescription
medications for insomnia; however, some recent clinical
guidelines do not recommend its use for treating insomnia.
This clinical appraisal critically reviews the scientific
literature on trazodone as a first-line treatment for
insomnia, with the focus statement "Trazodone should never
be used as a first-line medication for insomnia." In
addition, field surveys were sent to practicing physicians,
psychiatrists, and sleep specialists to assess general
support for this statement. Subsequently, a meeting with a
seven-member panel of key opinion leaders was held to
discuss published evidence in support and against the
statement. This paper reports on the evidence review, the
panel discussion, and the panel's and healthcare
professionals' ratings of the statement's acceptability.
While the majority of field survey responders disagreed with
the statement, the majority of panel members agreed with the
statement based on the limited published evidence supporting
trazodone as a first-line agent as they understood the term
"first-line agent".},
Doi = {10.3390/jcm12082933},
Key = {fds370751}
}
@article{fds369732,
Author = {Sellers, KK and Stapper, N and Astudillo Maya and DA and Henderson, C and Khambhati, AN and Fan, JM and Rao, VR and Scangos, KW and Chang, EF and Krystal, AD},
Title = {Changes in intracranial neurophysiology associated with
acute COVID-19 infection.},
Journal = {Clin Neurophysiol},
Volume = {148},
Pages = {29-31},
Year = {2023},
Month = {April},
url = {http://dx.doi.org/10.1016/j.clinph.2023.01.012},
Doi = {10.1016/j.clinph.2023.01.012},
Key = {fds369732}
}
@article{fds370425,
Author = {Watson, NF and Benca, RM and Krystal, AD and McCall, WV and Neubauer,
DN},
Title = {Alliance for Sleep Clinical Practice Guideline on Switching
or Deprescribing Hypnotic Medications for
Insomnia.},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {7},
Year = {2023},
Month = {March},
url = {http://dx.doi.org/10.3390/jcm12072493},
Abstract = {Determining the most effective insomnia medication for
patients may require therapeutic trials of different
medications. In addition, medication side effects,
interactions with co-administered medications, and declining
therapeutic efficacy can necessitate switching between
different insomnia medications or deprescribing altogether.
Currently, little guidance exists regarding the safest and
most effective way to transition from one medication to
another. Thus, we developed evidence-based guidelines to
inform clinicians regarding best practices when
deprescribing or transitioning between insomnia medications.
Five U.S.-based sleep experts reviewed the literature
involving insomnia medication deprescribing, tapering, and
switching and rated the quality of evidence. They used this
evidence to generate recommendations through discussion and
consensus. When switching or discontinuing insomnia
medications, we recommend benzodiazepine hypnotic drugs be
tapered while additional CBT-I is provided. For Z-drugs
zolpidem and eszopiclone (and not zaleplon), especially when
prescribed at supratherapeutic doses, tapering is
recommended with a 1-2-day delay in administration of the
next insomnia therapy when applicable. There is no need to
taper DORAs, doxepin, and ramelteon. Lastly, off-label
antidepressants and antipsychotics used to treat insomnia
should be gradually reduced when discontinuing. In general,
offering individuals a rationale for deprescribing or
switching and involving them in the decision-making process
can facilitate the change and enhance treatment
success.},
Doi = {10.3390/jcm12072493},
Key = {fds370425}
}
@article{fds370426,
Author = {Benca, RM and Bertisch, SM and Ahuja, A and Mandelbaum, R and Krystal,
AD},
Title = {Wake Up America: National Survey of Patients' and
Physicians' Views and Attitudes on Insomnia
Care.},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {7},
Year = {2023},
Month = {March},
url = {http://dx.doi.org/10.3390/jcm12072498},
Abstract = {While both patients and physicians consider sleep to be
important, sleep health may not receive appropriate
consideration during patient visits with health care
professionals (HCPs). We completed the first large-scale
survey of people with trouble sleeping (PWTS) and physicians
who treat insomnia to understand their perspectives and
potential discrepancies between them. The Harris Poll
conducted online surveys of adult PWTS and HCPs (primary
care physicians [PCPs] and psychiatrists) in the United
States from September to October 2021. Respondents included
1001 PWTS, 300 PCPs, and 152 psychiatrists. Most HCPs agreed
that sleep is critical to good health, yet very few reported
routinely conducting full sleep histories on their patients.
Approximately 30% of PWTS reported that their PCP never asks
about sleep; zero HCPs in this survey reported "never"
inquiring. Few HCPs reported being "very satisfied" with
current treatment options; 50% of PCPs reported their
patients being satisfied. Two-thirds of PWTS did not believe
current treatment options adequately improved their sleep.
This survey provides evidence that both PWTS and physicians
agreed on the importance of sleep, but that treatment is
often perceived as ineffective. This survey identifies a
need for HCPs to address insomnia management and treatment
gaps.},
Doi = {10.3390/jcm12072498},
Key = {fds370426}
}
@article{fds369966,
Author = {Morin, CM and Bertisch, SM and Pelayo, R and Watson, NF and Winkelman,
JW and Zee, PC and Krystal, AD},
Title = {What Should Be the Focus of Treatment When Insomnia Disorder
Is Comorbid with Depression or Anxiety Disorder?},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {5},
Year = {2023},
Month = {March},
url = {http://dx.doi.org/10.3390/jcm12051975},
Abstract = {Insomnia is a significant, highly prevalent, persistent
public health problem but often remains undiagnosed and
untreated. Current treatment practices are not always
evidence-based. When insomnia is comorbid with anxiety or
depression, treatment often targets that comorbid condition
with the expectation that improvement of the mental health
condition will generalize to sleep symptoms. An expert panel
of seven members conducted a clinical appraisal of the
literature regarding the treatment of insomnia when comorbid
anxiety or depression are also present. The clinical
appraisal consisted of the review, presentation, and
assessment of current published evidence as it relates to
the panel's predetermined clinical focus statement,
"Whenever chronic insomnia is associated with another
condition, such as anxiety or depression, that psychiatric
condition should be the only focus of treatment as the
insomnia is most likely a symptom of the condition". The
results from an electronic national survey of US-based
practicing physicians, psychiatrists, and sleep (N = 508)
revealed that >40% of physicians agree "at least somewhat"
that treatment of comorbid insomnia should focus solely on
the psychiatric condition. Whereas 100% of the expert panel
disagreed with the statement. Thus, an important gap exists
between current clinical practices and evidence-based
guidelines and more awareness is needed so that insomnia is
treated distinctly from comorbid anxiety and
depression.},
Doi = {10.3390/jcm12051975},
Key = {fds369966}
}
@article{fds369900,
Author = {Zee, PC and Bertisch, SM and Morin, CM and Pelayo, R and Watson, NF and Winkelman, JW and Krystal, AD},
Title = {Long-Term Use of Insomnia Medications: An Appraisal of the
Current Clinical and Scientific Evidence.},
Journal = {Journal of Clinical Medicine},
Volume = {12},
Number = {4},
Year = {2023},
Month = {February},
url = {http://dx.doi.org/10.3390/jcm12041629},
Abstract = {While evidence supports the benefits of medications for the
treatment of chronic insomnia, there is ongoing debate
regarding their appropriate duration of use. A panel of
sleep experts conducted a clinical appraisal regarding the
use of insomnia medications, as it relates to the evidence
supporting the focus statement, "No insomnia medication
should be used on a daily basis for durations longer than 3
weeks at a time". The panelists' assessment was also
compared to findings from a national survey of practicing
physicians, psychiatrists, and sleep specialists. Survey
respondents revealed a wide range of opinions regarding the
appropriateness of using the US Food and Drug Administration
(FDA)-approved medications for the treatment of insomnia
lasting more than 3 weeks. After discussion of the
literature, the panel unanimously agreed that some classes
of insomnia medications, such as non-benzodiazepines
hypnotics, have been shown to be effective and safe for
long-term use in the appropriate clinical setting. For
eszopiclone, doxepin, ramelteon and the newer class of dual
orexin receptor antagonists, the FDA label does not specify
that their use should be of a limited duration. Thus, an
evaluation of evidence supporting the long-term safety and
efficacy of newer non-benzodiazepine hypnotics is timely and
should be considered in practice recommendations for the
duration of pharmacologic treatment of chronic
insomnia.},
Doi = {10.3390/jcm12041629},
Key = {fds369900}
}
@article{fds369402,
Author = {Benca, RM and Krystal, A and Chepke, C and Doghramji,
K},
Title = {Recognition and Management of Obstructive Sleep Apnea in
Psychiatric Practice.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {84},
Number = {2},
Year = {2023},
Month = {January},
url = {http://dx.doi.org/10.4088/JCP.22r14521},
Abstract = {Objective: The aims of this review were to describe the
relationship between obstructive sleep apnea (OSA) and
psychiatric disorders and provide an overview of how to
recognize/manage OSA in psychiatric practice. Data Sources:
A literature search of PubMed was conducted (in adults,
English language, no limitation on year). Among others, main
keywords included "obstructive sleep apnea" AND
"psychiatric." Study Selection: Articles relevant to the
treatment of OSA in psychiatric populations were selected
manually. Data Extraction: No formal data charting was
conducted. Results: A total of 141 articles were included
from the literature search. Comorbid OSA is common among
patients with psychiatric disorders, particularly depression
and posttraumatic stress disorder. Evidence suggests that
OSA may be an independent risk factor for the development of
psychiatric conditions, as well as for suicidal ideation and
attempts in psychiatric populations. Recognizing OSA in
patients with psychiatric disorders can be challenging due
to the overlap of symptoms (eg, sleep issues, mood changes,
and vegetative symptoms) between OSA, psychiatric disorders,
and side effects of psychiatric medications. Inadequately
treated OSA can affect the severity of psychiatric symptoms
and impair response to psychiatric treatment. Conclusions:
Clinicians should not assume that all sleep-related symptoms
are consequences of psychiatric illness or medication but
should instead be cognizant of the potential for coexisting
OSA that requires treatment. Recognizing and managing OSA in
patients with psychiatric disorders are critical to improve
response to treatment, quality of life, and overall
health.},
Doi = {10.4088/JCP.22r14521},
Key = {fds369402}
}
@article{fds367831,
Author = {Ohayon, MM and McCue, M and Krystal, A and Selzler, KJ and Chrones, L and Lawrence, D and Côté, M-L},
Title = {Longitudinal study to assess antidepressant treatment
patterns and outcomes in individuals with depression in the
general population.},
Journal = {J Affect Disord},
Volume = {321},
Pages = {272-278},
Year = {2023},
Month = {January},
url = {http://dx.doi.org/10.1016/j.jad.2022.10.034},
Abstract = {BACKGROUND: Major depressive disorder (MDD) is largely
managed in primary care, but physicians vary widely in their
understanding of symptoms and treatments. This study aims to
better understand the evolution of depression from initial
diagnosis over a 3-year period. METHODS: This was a
noninterventional, retrospective, longitudinal study, with 2
waves of participant interviews approximately 3 years
apart. Phone interviews were conducted using the hybrid
artificial intelligence (AI) Sleep-EVAL system, an AI-driven
diagnostic deep learning tool. Participants were
noninstitutionalized adults representative of the general
population in 8 US states. Diagnosis was confirmed according
to the DSM-5 using the Sleep-EVAL System. RESULTS: 10,931
participants completed Wave 1 and 2 (W1, W2) interviews. The
prevalence of MDD, including partial and complete remission,
was 13.4 % and 19.6 % in W1 and W2, respectively. About
42 % of MDD participants at W1 continued to report
depressive symptoms at W2. Approximately half of
antidepressant (AD) users in W1 were moderately to
completely dissatisfied with their treatment; 29.6 %
changed their AD for a different one, with 16.4 % switching
from one SSRI to another between W1 and W2. Primary care
physicians were the top AD prescribers, both in W1 (45.7 %)
and W2 (59%), respectively. LIMITATIONS: Data collected
relied on self-reporting by participants. As such, the
interpretation of the data may be limited. CONCLUSIONS:
Depression affects a sizeable portion of the US population.
Dissatisfaction with treatment, frequent switching of ADs,
and changing care providers are associated with low rates of
remission. Residual symptoms remain a challenge that future
research must address.},
Doi = {10.1016/j.jad.2022.10.034},
Key = {fds367831}
}
@article{fds367452,
Author = {Epperson, CN and Rubinow, DR and Meltzer-Brody, S and Deligiannidis,
KM and Riesenberg, R and Krystal, AD and Bankole, K and Huang, M-Y and Li,
H and Brown, C and Kanes, SJ and Lasser, R},
Title = {Effect of brexanolone on depressive symptoms, anxiety, and
insomnia in women with postpartum depression: Pooled
analyses from 3 double-blind, randomized, placebo-controlled
clinical trials in the HUMMINGBIRD clinical
program.},
Journal = {J Affect Disord},
Volume = {320},
Pages = {353-359},
Year = {2023},
Month = {January},
url = {http://dx.doi.org/10.1016/j.jad.2022.09.143},
Abstract = {BACKGROUND: Brexanolone is currently the only treatment
specifically approved for postpartum depression (PPD) in the
United States, based on the results from one Phase 2 and two
Phase 3 double-blind, randomized, controlled trials in the
HUMMINGBIRD program. METHODS: Adults with PPD randomized to
a 60-h infusion of brexanolone 90 μg/kg/h (BRX90) or
placebo from the 3 trials were included in these post hoc
analyses. Data on change from baseline (CFB) in the 17-item
Hamilton Rating Scale for Depression (HAMD-17) total score,
HAMD-17 Anxiety/Somatization and Insomnia subscales, and
Clinical Global Impression of Improvement (CGI-I) scale were
pooled. Response rates for HAMD-17 (≥50 % reduction from
baseline) and CGI-I (score of 1 or 2) scales and time to
response were analyzed. RESULTS: Patients receiving BRX90
(n = 102) versus placebo (n = 107) achieved a more rapid
HAMD-17 response (median, 24 vs 36 h; p = 0.0265), with
an Hour-60 cumulative response rate of 81.4 % versus
67.3 %; results were similar for time to CGI-I response
(median, 24 vs 36 h; p = 0.0058), with an Hour-60
cumulative response rate of 81.4 % versus 61.7 %. CFB in
HAMD-17 Anxiety/Somatization and Insomnia subscales also
favored BRX90 versus placebo, starting at Hour 24 through
Day 30 (all p < 0.05), and response rates for both
subscales were higher with BRX90. LIMITATIONS: The study was
not powered to assess exploratory outcomes. CONCLUSIONS:
Brexanolone was associated with rapid improvement in
depressive symptoms and symptoms of anxiety and insomnia
compared with placebo in women with PPD. These data continue
to support the use of brexanolone to treat adults with
PPD.},
Doi = {10.1016/j.jad.2022.09.143},
Key = {fds367452}
}
@article{fds369901,
Author = {Fan, JM and Khambhati, AN and Sellers, KK and Stapper, N and Maya, DA and Kunwar, E and Henderson, C and Sugrue, LP and Scangos, KW and Chang, EF and Rao, VR and Krystal, AD},
Title = {Epileptiform discharges triggered with direct electrical
stimulation for treatment-resistant depression: Factors that
modulate risk and treatment considerations.},
Journal = {Brain Stimul},
Volume = {16},
Number = {2},
Pages = {462-465},
Year = {2023},
url = {http://dx.doi.org/10.1016/j.brs.2023.02.006},
Doi = {10.1016/j.brs.2023.02.006},
Key = {fds369901}
}
@article{fds366219,
Author = {Krystal, AD and Benca, RM and Rosenberg, R and Schweitzer, PK and Malhotra, A and Babson, K and Lee, L and Bujanover, S and Strohl,
KP},
Title = {Solriamfetol treatment of excessive daytime sleepiness in
participants with narcolepsy or obstructive sleep apnea with
a history of depression.},
Journal = {J Psychiatr Res},
Volume = {155},
Pages = {202-210},
Year = {2022},
Month = {November},
url = {http://dx.doi.org/10.1016/j.jpsychires.2022.08.018},
Abstract = {Given the high rate of depression associated with narcolepsy
or obstructive sleep apnea (OSA), this analysis compared
effects of solriamfetol treatment of excessive daytime
sleepiness (EDS) in participants with/without a history of
depression (DHx+/DHx-). This secondary analysis included
data from two randomized, controlled trials in which
participants were randomized to 12 weeks placebo or
solriamfetol 37.5 (OSA only), 75, 150, or 300 mg/day.
Efficacy/safety (combined solriamfetol doses) was summarized
for DHx+/DHx-subgroups. 27.5% (65/236) with narcolepsy and
23.4% (111/474) with OSA were DHx+. In narcolepsy (DHx+ and
DHx-), 40-min Maintenance of Wakefulness Test (MWT40) mean
sleep latency increased (5.4 and 7.0 min), Epworth
Sleepiness Scale (ESS) score decreased (3.8 and 3.5 points),
and percentage of participants improved on Patient Global
Impression of Change (PGI-C) was higher (31.7% and 39.4%)
relative to placebo. In OSA (DHx+ and DHx-), MWT40 mean
sleep latency increased (7.7 and 10.7 min), ESS decreased
(3.5 and 3.7 points), and percentage of participants
improved on PGI-C was higher (41.1% and 29.4%) relative to
placebo. Common treatment-emergent adverse events (headache,
decreased appetite, nausea, anxiety) were similar in
DHx+/DHx-. This study suggests that safety and efficacy of
solriamfetol for treating EDS in narcolepsy and OSA are not
affected by depression history. Moreover, the findings
emphasize the high prevalence of depression in people with
sleep disorders and suggest that increased awareness of this
association may have clinical significance.},
Doi = {10.1016/j.jpsychires.2022.08.018},
Key = {fds366219}
}
@article{fds365572,
Author = {Scangos, KW and Makhoul, GS and Sugrue, LP and Chang, EF and Krystal,
AD},
Title = {Publisher Correction: State-dependent responses to
intracranial brain stimulation in a patient with
depression.},
Journal = {Nat Med},
Volume = {28},
Number = {10},
Pages = {2218},
Year = {2022},
Month = {October},
url = {http://dx.doi.org/10.1038/s41591-022-01950-9},
Doi = {10.1038/s41591-022-01950-9},
Key = {fds365572}
}
@article{fds369121,
Author = {Chang, JL and Goldberg, AN and Alt, JA and Mohammed, A and Ashbrook, L and Auckley, D and Ayappa, I and Bakhtiar, H and Barrera, JE and Bartley,
BL and Billings, ME and Boon, MS and Bosschieter, P and Braverman, I and Brodie, K and Cabrera-Muffly, C and Caesar, R and Cahali, MB and Cai, Y and Cao, M and Capasso, R and Caples, SM and Chahine, LM and Chang, CP and Chang, KW and Chaudhary, N and Cheong, CSJ and Chowdhuri, S and Cistulli, PA and Claman, D and Collen, J and Coughlin, KC and Creamer,
J and Davis, EM and Dupuy-McCauley, KL and Durr, ML and Dutt, M and Ali,
ME and Elkassabany, NM and Epstein, LJ and Fiala, JA and Freedman, N and Gill, K and Gillespie, MB and Golisch, L and Gooneratne, N and Gottlieb,
DJ and Green, KK and Gulati, A and Gurubhagavatula, I and Hayward, N and Hoff, PT and Hoffmann, OMG and Holfinger, SJ and Hsia, J and Huntley, C and Huoh, KC and Huyett, P and Inala, S and Ishman, SL and Jella, TK and Jobanputra, AM and Johnson, AP and Junna, MR and Kado, JT and Kaffenberger, TM and Kapur, VK and Kezirian, EJ and Khan, M and Kirsch,
DB and Kominsky, A and Kryger, M and Krystal, AD and Kushida, CA and Kuzniar, TJ and Lam, DJ and Lettieri, CJ and Lim, DC and Lin, H-C and Liu,
SYC and MacKay, SG and Magalang, UJ and Malhotra, A and Mansukhani, MP and Maurer, JT and May, AM and Mitchell, RB and Mokhlesi, B and Mullins, AE and Nada, EM and Naik, S and Nokes, B and Olson, MD and Pack, AI and Pang, EB and Pang, KP and Patil, SP and Van de Perck and E and Piccirillo, JF and Pien,
GW and Piper, AJ and Plawecki, A and Quigg, M and Ravesloot, MJL and Redline, S and Rotenberg, BW and Ryden, A and Sarmiento, KF and Sbeih,
F and Schell, AE and Schmickl, CN and Schotland, HM and Schwab, RJ and Seo,
J and Shah, N and Shelgikar, AV and Shochat, I and Soose, RJ and Steele,
TO and Stephens, E and Stepnowsky, C and Strohl, KP and Sutherland, K and Suurna, MV and Thaler, E and Thapa, S and Vanderveken, OM and de Vries,
N and Weaver, EM and Weir, ID and Wolfe, LF and Woodson, BT and Won, CHJ and Xu, J and Yalamanchi, P and Yaremchuk, K and Yeghiazarians, Y and Yu,
JL and Zeidler, M and Rosen, IM},
Title = {International Consensus Statement on Obstructive Sleep
Apnea.},
Journal = {Int Forum Allergy Rhinol},
Year = {2022},
Month = {September},
url = {http://dx.doi.org/10.1002/alr.23079},
Abstract = {BACKGROUND: Evaluation and interpretation of the literature
on obstructive sleep apnea (OSA) allows for consolidation
and determination of the key factors important for clinical
management of the adult OSA patient. Toward this goal, an
international collaborative of multidisciplinary experts in
sleep apnea evaluation and treatment have produced the
International Consensus statement on Obstructive Sleep Apnea
(ICS:OSA). METHODS: Using previously defined methodology,
focal topics in OSA were assigned as literature review (LR),
evidence-based review (EBR), or evidence-based review with
recommendations (EBR-R) formats. Each topic incorporated the
available and relevant evidence which was summarized and
graded on study quality. Each topic and section underwent
iterative review and the ICS:OSA was created and reviewed by
all authors for consensus. RESULTS: The ICS:OSA addresses
OSA syndrome definitions, pathophysiology, epidemiology,
risk factors for disease, screening methods, diagnostic
testing types, multiple treatment modalities, and effects of
OSA treatment on multiple OSA-associated comorbidities.
Specific focus on outcomes with positive airway pressure
(PAP) and surgical treatments were evaluated. CONCLUSION:
This review of the literature consolidates the available
knowledge and identifies the limitations of the current
evidence on OSA. This effort aims to create a resource for
OSA evidence-based practice and identify future research
needs. Knowledge gaps and research opportunities include
improving the metrics of OSA disease, determining the
optimal OSA screening paradigms, developing strategies for
PAP adherence and longitudinal care, enhancing selection of
PAP alternatives and surgery, understanding health risk
outcomes, and translating evidence into individualized
approaches to therapy.},
Doi = {10.1002/alr.23079},
Key = {fds369121}
}
@article{fds363086,
Author = {Culpepper, L and Krystal, AD and Pinner, K and Moline,
M},
Title = {Post Hoc Analysis of the Impact of Lemborexant on
Patient-Reported Sleep and Insomnia Severity in Adults with
Insomnia and Depression Histories.},
Journal = {Cns Spectrums},
Volume = {27},
Number = {2},
Pages = {243},
Year = {2022},
Month = {April},
url = {http://dx.doi.org/10.1017/S1092852922000499},
Abstract = {INTRODUCTION: The dual orexin receptor antagonist
lemborexant (LEM) is approved in multiple countries
including the United States, Japan, Canada, and Australia
for insomnia treatment in adults. In phase 3 study
E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), LEM
provided significant benefit vs placebo (PBO) on subjective
sleep outcomes over 6 months and was well tolerated. This
post hoc analysis evaluated the effect of LEM on sleep
outcome measures and insomnia severity as assessed by the
Insomnia Severity Index (ISI) over 6 months in subjects
with a lifetime history of depression (DepHx subgroup). We
performed this analysis as insomnia in DepHx subjects could
be a residual symptom of unresolved depression, and
therefore, these subjects may respond differently to
insomnia treatment. METHODS: Study 303 was a randomized,
double-blind, 12 months global study in adults
(≥18 years) with DSM-5 insomnia disorder. For 6 months
(Treatment Period 1), subjects were randomized to PBO or LEM
(5 mg [LEM5]; 10 mg [LEM10]). For the next 6 months
(Treatment Period 2; not reported), PBO subjects were
rerandomized to LEM and LEM subjects continued their
original dose. The inclusion criteria allowed for
participation of subjects with a lifetime DepHx, concomitant
antidepressant medication use and/or mild depression
(maximum Beck Depression Inventory II score of 19). Subjects
had a baseline ISI total score (ISI-ts) ≥15. RESULTS: The
Full Analysis Set comprised 949 subjects, including 112
subjects in the DepHx subgroup (PBO, n = 34; LEM5,
n = 39; LEM10, n = 39). Baseline median subjective sleep
onset latency (sSOL; minutes) was 52.9, 57.1, and 70.7 for
PBO, LEM5, and LEM10, respectively. At 6 months, greater
median decreases from baseline in sSOL were observed with
LEM5 (-21.7) and LEM10 (-40.1) vs PBO (-12.9). Baseline mean
subjective sleep efficiency (sSE; %) was 62.2, 59.2, and
62.4 for PBO, LEM5, and LEM10, respectively. At 6 months,
greater mean (SD) increases from baseline in sSE were
observed with LEM5 (17.2 [18.3]) and LEM10 (20.9 [19.0]) vs
PBO (14.9 [15.4]). Baseline mean subjective wake after sleep
onset (sWASO; minutes) was 123.7, 151.0, and 132.6 for PBO,
LEM5, and LEM10, respectively. At 6 months, greater mean
(SD) decreases from baseline in sWASO were observed with
LEM5 (-52.7 [69.2]) and LEM10 (-68.8 [81.9]) vs PBO (-46.7
[69.4]). Mean baseline ISI-ts were 18.6, 19.9, and 19.0 PBO,
LEM5, and LEM10, respectively. At 6 months, greater mean
(SD) decreases from baseline in ISI-ts were observed with
LEM5 (-9.1 [6.8]) and LEM10 (-10.0 [5.9]) vs PBO (-7.9
[5.6]). Treatment-emergent adverse event rates in the DepHx
subgroup were similar to those in the overall study
population. DISCUSSION: At 6 months, LEM improved
patient-reported sleep outcomes and reduced patient-reported
insomnia severity in subjects with DepHx. These results
suggest that LEM may be a therapeutic option for patients
with insomnia and DepHx. FUNDING: Eisai,
Inc.},
Doi = {10.1017/S1092852922000499},
Key = {fds363086}
}
@article{fds363016,
Author = {Felder, JN and Mirchandaney, R and Harrison, J and Manber, R and Cuneo,
J and Krystal, A and Epel, E and Hecht, F},
Title = {Examining Experiences of Poor Sleep During Pregnancy: A
Qualitative Study to Inform the Development of a Prenatal
Sleep Intervention},
Journal = {Global Advances in Health and Medicine},
Volume = {11},
Year = {2022},
Month = {March},
url = {http://dx.doi.org/10.1177/2164957X221087655},
Abstract = {Background: Poor sleep is common during pregnancy and is
associated with increased risk of negative health outcomes.
Research indicates that physical discomfort and having an
active mind are primary factors for prenatal sleep
disturbances. Mindfulness-based interventions have the
potential for addressing these factors, but have yet to be
optimized for this purpose in this population. Objective:
The objective of this study was to gather input from
pregnant and postpartum individuals about the value of a
mindfulness-based program for improving prenatal sleep and
their preferred content and delivery format. Methods: We
conducted 2 focus groups with 12 pregnant people
experiencing poor sleep quality and 3 individual interviews
with postpartum people. Interviews were thematically
analyzed. Results: The majority of participants expressed
strong interest in a mindfulness program for improving
prenatal sleep. Participants reported that
pregnancy-specific physical discomfort and worry (both
general and pregnancy-specific) affected their sleep.
Participants wanted sleep education, and strategies for
calming the mind, reducing physical discomfort, reducing
impact of bedtime partners on sleep, and tips for improving
sleep schedule and quality. Participants recognized the
convenience of an online intervention and the social
benefits of an in-person intervention and favored a hybrid
delivery model. Conclusion: Addressing prenatal sleep
problems is an unmet need. Given the challenges and
discomfort women face during pregnancy, and the importance
of adequate sleep for promoting mental and physical health
during pregnancy, sleep difficulties are critical to
address. A mindfulness-based intervention for improving
prenatal sleep was deemed of high interest to this perinatal
population.},
Doi = {10.1177/2164957X221087655},
Key = {fds363016}
}
@article{fds361216,
Author = {Sforzini, L and Worrell, C and Kose, M and Anderson, IM and Aouizerate,
B and Arolt, V and Bauer, M and Baune, BT and Blier, P and Cleare, AJ and Cowen, PJ and Dinan, TG and Fagiolini, A and Ferrier, IN and Hegerl, U and Krystal, AD and Leboyer, M and McAllister-Williams, RH and McIntyre,
RS and Meyer-Lindenberg, A and Miller, AH and Nemeroff, CB and Normann,
C and Nutt, D and Pallanti, S and Pani, L and Penninx, BWJH and Schatzberg,
AF and Shelton, RC and Yatham, LN and Young, AH and Zahn, R and Aislaitner,
G and Butlen-Ducuing, F and Fletcher, C and Haberkamp, M and Laughren,
T and Mäntylä, F-L and Schruers, K and Thomson, A and Arteaga-Henríquez, G and Benedetti, F and Cash-Gibson, L and Chae,
WR and De Smedt and H and Gold, SM and Hoogendijk, WJG and Mondragón, VJ and Maron, E and Martynowicz, J and Melloni, E and Otte, C and Perez-Fuentes, G and Poletti, S and Schmidt, ME and van de Ketterij,
E and Woo, K and Flossbach, Y and Ramos-Quiroga, JA and Savitz, AJ and Pariante, CM},
Title = {A Delphi-method-based consensus guideline for definition of
treatment-resistant depression for clinical
trials.},
Journal = {Mol Psychiatry},
Volume = {27},
Number = {3},
Pages = {1286-1299},
Year = {2022},
Month = {March},
url = {http://dx.doi.org/10.1038/s41380-021-01381-x},
Abstract = {Criteria for treatment-resistant depression (TRD) and
partially responsive depression (PRD) as subtypes of major
depressive disorder (MDD) are not unequivocally defined. In
the present document we used a Delphi-method-based consensus
approach to define TRD and PRD and to serve as operational
criteria for future clinical studies, especially if
conducted for regulatory purposes. We reviewed the
literature and brought together a group of international
experts (including clinicians, academics, researchers,
employees of pharmaceutical companies, regulatory bodies
representatives, and one person with lived experience) to
evaluate the state-of-the-art and main controversies
regarding the current classification. We then provided
recommendations on how to design clinical trials, and on how
to guide research in unmet needs and knowledge gaps. This
report will feed into one of the main objectives of the
EUropean Patient-cEntric clinicAl tRial pLatforms,
Innovative Medicines Initiative (EU-PEARL, IMI) MDD project,
to design a protocol for platform trials of new medications
for TRD/PRD.},
Doi = {10.1038/s41380-021-01381-x},
Key = {fds361216}
}
@article{fds361879,
Author = {Whitehurst, LN and Subramoniam, A and Krystal, A and Prather,
AA},
Title = {Links between the brain and body during sleep: implications
for memory processing.},
Journal = {Trends Neurosci},
Volume = {45},
Number = {3},
Pages = {212-223},
Year = {2022},
Month = {March},
url = {http://dx.doi.org/10.1016/j.tins.2021.12.007},
Abstract = {Sleep is intimately related to memory processes. The
established view is that the transformation of experiences
into long-term memories is linked to sleep-related CNS
function. However, there is increasing evidence that the
autonomic nervous system (ANS), long recognized to modulate
cognition during waking, can impact memory processing during
sleep. Here, we review human research that examines the role
of autonomic activity and sleep in memory formation. We
argue that autonomic activity during sleep may set the stage
for the CNS dynamics associated with sleep and memory
stability and integration. Further, we consider how the link
between ANS activity and polysomnographic markers of sleep
may help elucidate both healthy and pathological cognitive
aging in humans.},
Doi = {10.1016/j.tins.2021.12.007},
Key = {fds361879}
}
@article{fds362188,
Author = {Felder, JN and Epel, ES and Neuhaus, J and Krystal, AD and Prather,
AA},
Title = {Randomized controlled trial of digital cognitive behavior
therapy for prenatal insomnia symptoms: effects on
postpartum insomnia and mental health.},
Journal = {Sleep},
Volume = {45},
Number = {2},
Year = {2022},
Month = {February},
url = {http://dx.doi.org/10.1093/sleep/zsab280},
Abstract = {STUDY OBJECTIVES: To evaluate the effects of digital
cognitive behavior therapy for insomnia (dCBT-I) delivered
during pregnancy on subjective sleep outcomes, depressive
symptoms, and anxiety symptoms through 6 months postpartum.
METHODS: People up to 28 weeks gestation (N = 208) with
insomnia were randomized to 6 weekly sessions of dCBT-I or
standard care. We report follow-up data at 3 and 6 months
postpartum. The primary outcome was insomnia symptom
severity. Secondary sleep outcomes included global sleep
quality and insomnia caseness. Mental health outcomes
included depressive and anxiety symptom severity. We
evaluated between-condition differences in change from
baseline for each postpartum timepoint and categorical
outcomes. RESULTS: dCBT-I participants did not experience
significantly greater improvements in insomnia symptom
severity relative to standard care participants, but they
did experience higher rates of insomnia remission and lower
rates of insomnia caseness at 6 months postpartum. dCBT-I
participants experienced greater improvements in depressive
symptom severity from baseline to both postpartum
timepoints, and in anxiety symptom severity from baseline to
3 months postpartum. The proportion of participants with
probable major depression at 3 months postpartum was
significantly higher among standard care (18%) than dCBT-I
(4%, p = 0.006) participants; this between-condition
difference was pronounced among the subset (n = 143) with
minimal depressive symptoms at baseline (18% vs 0%).
CONCLUSION: dCBT-I use during pregnancy leads to enduring
benefits for postpartum insomnia remission. Findings provide
strong preliminary evidence that dCBT-I use during pregnancy
may prevent postpartum depression and anxiety, which is
notable when considering the high frequency and importance
of these problems.Clinical Trials: ClinicalTrials.gov,
https://clinicaltrials.gov/ct2/show/NCT02805998,
NCT02805998.},
Doi = {10.1093/sleep/zsab280},
Key = {fds362188}
}
@article{fds361842,
Author = {Arnedt, JT and Cardoni, ME and Conroy, DA and Graham, M and Amin, S and Bohnert, KM and Krystal, AD and Ilgen, MA},
Title = {Telemedicine-delivered cognitive-behavioral therapy for
insomnia in alcohol use disorder (AUD): study protocol for a
randomized controlled trial.},
Journal = {Trials},
Volume = {23},
Number = {1},
Pages = {59},
Year = {2022},
Month = {January},
url = {http://dx.doi.org/10.1186/s13063-021-05898-y},
Abstract = {BACKGROUND: Alcohol use disorder (AUD) is a leading
preventable cause of morbidity and mortality, but relapse
rates are high even with available treatments. Insomnia is a
robust predictor of relapse and pilot studies have shown
that CBT for insomnia improves insomnia and daytime
functioning in adults with AUD and insomnia. The impact of
CBT for insomnia on relapse, however, is unclear. This trial
will compare telemedicine-delivered CBT for insomnia
(CBT-TM) with sleep hygiene education (SHE-TM) on improving
insomnia/sleep, daytime symptom, and drinking outcomes in
treatment-seeking AUD adults with insomnia. The study will
also determine the effects of treatment on sleep mechanisms
and their association with clinical outcomes. METHODS: This
is a single-site randomized controlled trial with planned
enrollment of 150 adults meeting criteria for both AUD and
chronic insomnia. Eligible participants will be randomized
1:1 to 6 sessions of telemedicine-delivered Cognitive
Behavioral Therapy for Insomnia (CBT-TM) or Sleep Hygiene
Education (SHE-TM) with clinical assessments conducted at
pre-treatment, post- treatment, and at 3, 6, and 12 months
post-treatment. Overnight polysomnography will be conducted
before and after treatment. Primary clinical outcomes will
include post-treatment scores on the Insomnia Severity Index
and the General Fatigue subscale of the Multidisciplinary
Fatigue Inventory, and the percent of days abstinent (PDA)
on the interview-administered Time Line Follow Back. EEG
delta activity, derived from overnight polysomnography, will
be the primary endpoint to assess the sleep homeostasis
mechanism. DISCUSSION: This adequately powered randomized
controlled trial will provide clinically relevant
information about whether targeting insomnia is effective
for improving treatment outcomes among treatment-seeking
adults with AUD. Additionally, the study will offer new
scientific insights on the impact of an evidence-based
non-medication treatment for insomnia on a candidate
mechanism of sleep dysfunction in this population - sleep
homeostasis. TRIAL REGISTRATION: CClinicalTrials.gov NCT #
04457674 . Registered on 07 July 2020.},
Doi = {10.1186/s13063-021-05898-y},
Key = {fds361842}
}
@article{fds362128,
Author = {Wickwire, EM and Albrecht, JS and Capaldi, VF and Jain, SO and Gardner,
RC and Werner, JK and Mukherjee, P and McKeon, AB and Smith, MT and Giacino, JT and Nelson, LD and Williams, SG and Collen, J and Sun, X and Schnyer, DM and Markowitz, AJ and Manley, GT and Krystal, AD and Transforming Research and Clinical Knowledge in Traumatic
Brain Injury (TRACK-TBI) Investigators},
Title = {Trajectories of Insomnia in Adults After Traumatic Brain
Injury.},
Journal = {Jama Network Open},
Volume = {5},
Number = {1},
Pages = {e2145310},
Year = {2022},
Month = {January},
url = {http://dx.doi.org/10.1001/jamanetworkopen.2021.45310},
Abstract = {IMPORTANCE: Insomnia is common after traumatic brain injury
(TBI) and contributes to morbidity and long-term sequelae.
OBJECTIVE: To identify unique trajectories of insomnia in
the 12 months after TBI. DESIGN, SETTING, AND PARTICIPANTS:
In this prospective cohort study, latent class mixed models
(LCMMs) were used to model insomnia trajectories over time
and to classify participants into distinct profile groups.
Data from the Transforming Research and Clinical Knowledge
in Traumatic Brain Injury (TRACK-TBI) study, a longitudinal,
multisite, observational study, were uploaded to the Federal
Interagency Traumatic Brain Injury Repository (FITBIR)
database. Participants were enrolled at 1 of 18
participating level I trauma centers and enrolled within 24
hours of TBI injury. Additional data were obtained directly
from the TRACK-TBI investigators that will be uploaded to
FITBIR in the future. Data were collected from February 26,
2014, to August 8, 2018, and analyzed from July 1, 2020, to
November 15, 2021. EXPOSURES: Traumatic brain injury. MAIN
OUTCOMES AND MEASURES: Insomnia Severity Index assessed
serially at 2 weeks and 3, 6, and 12 months thereafter.
RESULTS: The final sample included 2022 participants (1377
[68.1%] men; mean [SD] age, 40.1 [17.2] years) from the
FITBIR database and the TRACK-TBI study. The data were best
fit by a 5-class LCMM. Of these participants, 1245 (61.6%)
reported persistent mild insomnia symptoms (class 1); 627
(31.0%) initially reported mild insomnia symptoms that
resolved over time (class 2); 91 (4.5%) reported persistent
severe insomnia symptoms (class 3); 44 (2.2%) initially
reported severe insomnia symptoms that resolved by 12 months
(class 4); and 15 (0.7%) initially reported no insomnia
symptoms but had severe symptoms by 12 months (class 5). In
a multinomial logistic regression model, several factors
significantly associated with insomnia trajectory class
membership were identified, including female sex (odds ratio
[OR], 1.65 [95% CI, 1.02-2.66]), Black race (OR, 2.36 [95%
CI, 1.39-4.01]), history of psychiatric illness (OR, 2.21
[95% CI, 1.35-3.60]), and findings consistent with
intracranial injury on computed tomography (OR, 0.36 [95%
CI, 0.20-0.65]) when comparing class 3 with class 1.
CONCLUSIONS AND RELEVANCE: These results suggest important
heterogeneity in the course of insomnia after TBI in adults.
More work is needed to identify outcomes associated with
these insomnia trajectory class subgroups and to identify
optimal subgroup-specific treatment approaches.},
Doi = {10.1001/jamanetworkopen.2021.45310},
Key = {fds362128}
}
@article{fds362388,
Author = {Lunsford-Avery, JR and Edinger, JD and Krystal,
AD},
Title = {Overnight Delta Dynamics Associated with Daytime Psychomotor
Performance in Adults with Insomnia and Healthy
Controls.},
Journal = {Nature and Science of Sleep},
Volume = {14},
Pages = {217-230},
Year = {2022},
url = {http://dx.doi.org/10.2147/NSS.S330939},
Abstract = {PURPOSE: Sleep is vital to cognition, yet underlying
mechanisms remain unclear. Although sleep duration and
continuity are two well-established contributors, additional
factors-including homeostatic sleep drive processes-may also
underlie cognition-related sleep restoration. This study
investigates the relative contributions of sleep EEG factors
to psychomotor functioning in adults with insomnia and
healthy controls (HC) to identify the most significant sleep
factors supporting psychomotor functioning. MATERIALS AND
METHODS: Adults with insomnia (n = 37) and HC (n = 39)
completed 3 nights of polysomnography and a complex
psychomotor task (switching attention task; SAT). Univariate
correlations identified the most significant predictors
(traditional PSG, spectral EEG, initial delta peak, and
overnight delta decline) of SAT performance, which were then
entered into multivariable linear regressions examining
whether predictors remained significant after accounting for
shortened/fragmented sleep and whether relationships
differed across groups. RESULTS: In addition to greater wake
after sleep onset (WASO; r = 0.33), a slower overnight delta
decline (r = 0.50) and a lower initial delta peak (r =
-0.38) were the most significant predictors of poorer SAT
performance. Both overnight delta decline (F(7, 68) = 12.52,
p < 0.001) and initial delta peak (F(7, 68) = 7.85, p =
0.007) remained significant predictors after controlling for
demographics, total sleep time, and WASO. Relationships were
analogous across subject groups. CONCLUSION: Findings
suggest that, in addition to sleep duration and continuity,
processes related to recovery from and dissipation of
homeostatic sleep drive may support psychomotor performance
and broadly support daytime functioning in individuals with
and without insomnia. Future research may examine overnight
delta dynamics as transdiagnostic processes supporting
cognition-related sleep restoration across a range of
clinical populations.},
Doi = {10.2147/NSS.S330939},
Key = {fds362388}
}
@article{fds361321,
Author = {Krystal, AD and Ashbrook, LH and Prather, AA},
Title = {What Is Insomnia?},
Journal = {Jama},
Volume = {326},
Number = {23},
Pages = {2444},
Year = {2021},
Month = {December},
url = {http://dx.doi.org/10.1001/jama.2021.19283},
Doi = {10.1001/jama.2021.19283},
Key = {fds361321}
}
@article{fds357945,
Author = {McCall, WV and Porter, B and Pate, AR and Bolstad, CJ and Drapeau, CW and Krystal, AD and Benca, RM and Rumble, ME and Nadorff,
MR},
Title = {Examining suicide assessment measures for research use:
Using item response theory to optimize psychometric
assessment for research on suicidal ideation in major
depressive disorder.},
Journal = {Suicide and Life Threatening Behavior},
Volume = {51},
Number = {6},
Pages = {1086-1094},
Year = {2021},
Month = {December},
url = {http://dx.doi.org/10.1111/sltb.12791},
Abstract = {INTRODUCTION: Progress reducing suicide death will require
randomized clinical trials (RCTs) specifically targeting
suicide risk. Even large RCTs may not stipulate suicide
death as the primary outcome, as suicide death is relatively
uncommon. Therefore, RCTs may need to specify suicidal
ideation as a proxy indicator of risk. There is no consensus
on the best tool for measuring suicidal ideation within
RCTs. We contrasted the psychometric performance of three
suicidal ideation measures to address this need. METHODS: We
applied item response theory to the Beck Scale for Suicide
Ideation (BSSI), the Columbia-Suicide Severity Rating Scale
(C-SSRS), and the suicide item of the Hamilton Rating Scale
for Depression (HRSD) for 101 outpatients with depression
and suicidal ideation participating in a RCT with suicidal
ideation as the primary outcome. RESULTS: All measures of
suicidal ideation were equally able to detect low and very
high levels of suicidal ideation. CONCLUSIONS: The choice of
the specific measure of suicidal ideation in a clinical
trial may be dictated by time and financial resources versus
the need for granularity in the interpretation of the
scores.},
Doi = {10.1111/sltb.12791},
Key = {fds357945}
}
@article{fds358720,
Author = {Pizzagalli, DA and Smoski, M and Ang, Y-S and Whitton, AE and Sanacora,
G and Mathew, SJ and Nurnberger, J and Lisanby, SH and Iosifescu, DV and Murrough, JW and Yang, H and Weiner, RD and Calabrese, JR and Goodman,
W and Potter, WZ and Krystal, AD},
Title = {Correction to: Selective kappa-opioid antagonism ameliorates
anhedonic behavior: evidence from the Fast-fail Trial in
Mood and Anxiety Spectrum Disorders (FAST-MAS).},
Journal = {Neuropsychopharmacology},
Volume = {46},
Number = {12},
Pages = {2224},
Year = {2021},
Month = {November},
url = {http://dx.doi.org/10.1038/s41386-021-01145-9},
Doi = {10.1038/s41386-021-01145-9},
Key = {fds358720}
}
@article{fds359638,
Author = {Scangos, KW and Khambhati, AN and Daly, PM and Makhoul, GS and Sugrue,
LP and Zamanian, H and Liu, TX and Rao, VR and Sellers, KK and Dawes, HE and Starr, PA and Krystal, AD and Chang, EF},
Title = {Closed-loop neuromodulation in an individual with
treatment-resistant depression.},
Journal = {Nat Med},
Volume = {27},
Number = {10},
Pages = {1696-1700},
Year = {2021},
Month = {October},
url = {http://dx.doi.org/10.1038/s41591-021-01480-w},
Abstract = {Deep brain stimulation is a promising treatment for
neuropsychiatric conditions such as major depression. It
could be optimized by identifying neural biomarkers that
trigger therapy selectively when symptom severity is
elevated. We developed an approach that first used multi-day
intracranial electrophysiology and focal electrical
stimulation to identify a personalized symptom-specific
biomarker and a treatment location where stimulation
improved symptoms. We then implanted a chronic deep brain
sensing and stimulation device and implemented a
biomarker-driven closed-loop therapy in an individual with
depression. Closed-loop therapy resulted in a rapid and
sustained improvement in depression. Future work is required
to determine if the results and approach of this n-of-1
study generalize to a broader population.},
Doi = {10.1038/s41591-021-01480-w},
Key = {fds359638}
}
@article{fds359121,
Author = {Krystal, JH and Chow, B and Vessicchio, J and Henrie, AM and Neylan, TC and Krystal, AD and Marx, BP and Xu, K and Jindal, RD and Davis, LL and Schnurr, PP and Stein, MB and Thase, ME and Ventura, B and Huang, GD and Shih, M-C and CSP 2016 Study Team},
Title = {Design of the National Adaptive Trial for PTSD-related
Insomnia (NAP Study), VA Cooperative Study Program (CSP)
#2016.},
Journal = {Contemp Clin Trials},
Volume = {109},
Pages = {106540},
Year = {2021},
Month = {October},
url = {http://dx.doi.org/10.1016/j.cct.2021.106540},
Abstract = {There are currently no validated pharmacotherapies for
posttraumatic stress disorder (PTSD)-related insomnia. The
purpose of the National Adaptive Trial for PTSD-Related
Insomnia (NAP Study) is to efficiently compare to placebo
the effects of three insomnia medications with different
mechanisms of action that are already prescribed widely to
veterans diagnosed with PTSD within U.S. Department of
Veterans Affairs (VA) Medical Centers. This study plans to
enroll 1224 patients from 34 VA Medical Centers into a 12-
week prospective, randomized placebo-controlled clinical
trial comparing trazodone, eszopiclone, and gabapentin. The
primary outcome measure is insomnia, assessed with the
Insomnia Severity Index. A novel aspect of this study is its
adaptive design. At the recruitment midpoint, an interim
analysis will be conducted to inform a decision to close
recruitment to any "futile" arms (i.e. arms where further
recruitment is very unlikely to yield a significant result)
while maintaining the overall study recruitment target. This
step could result in the enrichment of the remaining study
arms, enhancing statistical power for the remaining
comparisons to placebo. This study will also explore
clinical, actigraphic, and biochemical predictors of
treatment response that may guide future biomarker
development. Lastly, due to the COVID-19 pandemic, this
study will allow the consenting process and follow-up visits
to be conducted via video or phone contact if in-person
meetings are not possible. Overall, this study aims to
identify at least one effective pharmacotherapy for
PTSD-related insomnia, and, perhaps, to generate definitive
negative data to reduce the use of ineffective insomnia
medications. NATIONAL CLINICAL TRIAL (NCT) IDENTIFIED
NUMBER: NCT03668041.},
Doi = {10.1016/j.cct.2021.106540},
Key = {fds359121}
}
@article{fds363087,
Author = {Rosenberg, RP and Krystal, AD},
Title = {Diagnosing and Treating Insomnia in Adults and Older
Adults.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {82},
Number = {6},
Year = {2021},
Month = {September},
url = {http://dx.doi.org/10.4088/JCP.EI20008AH5C},
Abstract = {Insomnia, the most prevalent sleep-wake disorder, affects 6%
to 10% of adults. It may result in interpersonal and
occupational problems and has a deleterious effect on
quality of life. Patients may experience difficulty with
sleep onset, sleep maintenance, or both. Insomnia disorder
is commonly comorbid with psychiatric, medical, and
neurologic disorders, and insomnia and comorbid conditions
have bidirectional relationships. Diagnosis should be based
on patient interview, assessment with tools, and use of
criteria. Selection of treatment for patients with insomnia
should factor in efficacy for the patient's specific
complaint as well as other features such as safety profile
and abuse liability. Cognitive-behavioral therapy for
insomnia is a first-line recommendation by guidelines, but
some patients are unable or unwilling to try it or may not
respond to it. Older adults with insomnia disorder require
careful consideration of medications' risk-benefit
profiles.},
Doi = {10.4088/JCP.EI20008AH5C},
Key = {fds363087}
}
@article{fds363088,
Author = {Krystal, AD},
Title = {Optimizing Treatment for Insomnia.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {82},
Number = {4},
Pages = {EI20008BR4C},
Year = {2021},
Month = {July},
url = {http://dx.doi.org/10.4088/JCP.EI20008BR4C},
Abstract = {By tailoring the mechanism of action and effects of therapy
to the specific nature of each patient's insomnia and other
conditions, clinicians can offer personalized care in an
attempt to achieve an improved risk-benefit ratio compared
to that of a "one-size-fits-all" treatment strategy. To move
toward this personalization and optimization of treatment,
clinicians need awareness of the specific effects of
interventions and the subpopulations with insomnia who would
benefit from each intervention. This report reviews insomnia
treatments, focusing on effects associated with mechanism of
action.},
Doi = {10.4088/JCP.EI20008BR4C},
Key = {fds363088}
}
@article{fds358386,
Author = {Insel, PS and Mohlenhoff, BS and Neylan, TC and Krystal, AD and Mackin,
RS},
Title = {Association of Sleep and β-Amyloid Pathology Among Older
Cognitively Unimpaired Adults.},
Journal = {Jama Network Open},
Volume = {4},
Number = {7},
Pages = {e2117573},
Year = {2021},
Month = {July},
url = {http://dx.doi.org/10.1001/jamanetworkopen.2021.17573},
Abstract = {IMPORTANCE: Disrupted sleep commonly occurs with progressing
neurodegenerative disease. Large, well-characterized
neuroimaging studies of cognitively unimpaired adults are
warranted to clarify the magnitude and onset of the
association between sleep and emerging β-amyloid (Aβ)
pathology. OBJECTIVE: To evaluate the associations between
daytime and nighttime sleep duration with regional Aβ
pathology in older cognitively unimpaired adults. DESIGN,
SETTING, AND PARTICIPANTS: In this cross-sectional study,
screening data were collected between April 1, 2014, and
December 31, 2017, from healthy, cognitively unimpaired
adults 65 to 85 years of age who underwent florbetapir F 18
positron emission tomography (PET), had APOE genotype
information, scored between 25 and 30 on the Mini-Mental
State Examination, and had a Clinical Dementia Rating of 0
for the Anti-Amyloid Treatment in Asymptomatic Alzheimer
Disease (A4) Study. Data analysis was performed from
December 1, 2019, to May 10, 2021. EXPOSURES: Self-reported
daytime and nighttime sleep duration. MAIN OUTCOMES AND
MEASURES: Regional Aβ pathology, measured by florbetapir
PET standardized uptake value ratio. RESULTS: Amyloid PET
and sleep duration information was acquired on 4425
cognitively unimpaired participants (mean [SD] age, 71.3
[4.7] years; 2628 [59.4%] female; 1509 [34.1%] tested Aβ
positive). Each additional hour of nighttime sleep was
associated with a 0.005 reduction of global Aβ standardized
uptake value ratio (F1, 4419 = 5.0; P = .03), a
0.009 reduction of medial orbitofrontal Aβ (F1,
4419 = 17.4; P < .001), and a 0.011 reduction of
anterior cingulate Aβ (F1, 4419 = 15.9; P < .001).
When restricting analyses to participants who tested Aβ
negative, nighttime sleep was associated with a 0.006
reduction of medial orbitofrontal Aβ (F1,2910 = 16.9;
P < .001) and a 0.005 reduction of anterior cingulate
Aβ (F1,2910 = 7.6; P = .03). Daytime sleep was
associated with a 0.013 increase of precuneus Aβ
(F1,2910 = 7.3; P = .03) and a 0.024 increase of
posterior cingulate Aβ (F1,2910 = 14.2; P = .001)
in participants who tested Aβ negative. CONCLUSIONS AND
RELEVANCE: In this cross-sectional study, the increased risk
of Aβ deposition with reduced nighttime sleep duration
occurred early, before cognitive impairment or significant
Aβ deposition. Daytime sleep may be associated with an
increase in risk for early Aβ accumulation and did not
appear to be corrective for loss of nighttime sleep,
demonstrating a circadian rhythm dependence of sleep in
preventing Aβ accumulation. Treatments that improve sleep
may reduce early Aβ accumulation and aid in delaying the
onset of cognitive dysfunction associated with early
Alzheimer disease.},
Doi = {10.1001/jamanetworkopen.2021.17573},
Key = {fds358386}
}
@article{fds356161,
Author = {Zammit, G and Krystal, A},
Title = {Evaluating lemborexant for the treatment of
insomnia.},
Journal = {Expert Opinion on Pharmacotherapy},
Volume = {22},
Number = {10},
Pages = {1235-1243},
Year = {2021},
Month = {July},
url = {http://dx.doi.org/10.1080/14656566.2021.1902987},
Abstract = {<h4>Introduction</h4>Insomnia is a complex sleep disorder
that compromises quality of life and affects approximately
10% of the general population. Insomnia, defined as trouble
initiating or maintaining sleep associated with impaired
daytime function or distress, is treated using a
comprehensive approach comprised of cognitive behavioral
therapy and pharmacotherapy. Lemborexant, a dual orexin
receptor antagonist, is a new pharmacotherapeutic option
recently approved for the treatment of insomnia.<h4>Areas
covered</h4>Here, the authors describe lemborexant, assess
its efficacy and safety profile in clinical trials, and
evaluate its role in the current insomnia treatment
landscape.<h4>Expert opinion</h4>Lemborexant may offer an
improved treatment option compared with other
pharmacotherapies for insomnia because it is effective both
over the long term and over a wide range of outcome
measures. Importantly, lemborexant improves latency to sleep
onset and sleep maintenance and is able to help people who
experience early morning awakenings. Safety data reveal that
lemborexant has minimal residual effects on morning
alertness or next day function, and that patients are able
to respond to an external auditory stimulus in the middle of
the night. In conclusion, lemborexant represents a new,
effective, and well-tolerated medication for patients with
insomnia.},
Doi = {10.1080/14656566.2021.1902987},
Key = {fds356161}
}
@article{fds363089,
Author = {Krystal, AD},
Title = {Challenges in Managing Insomnia in Older
People.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {82},
Number = {4},
Year = {2021},
Month = {June},
url = {http://dx.doi.org/10.4088/JCP.EI20008BR3C},
Abstract = {Older people often experience insomnia, whether it is
difficulty initiating or maintaining sleep. These sleep
disturbances have a negative impact on quality of life and
functioning. This report offers general considerations as
well as specific data related to managing insomnia in older
adults, including a brief review of treatment options with
an emphasis on their tolerability profiles.},
Doi = {10.4088/JCP.EI20008BR3C},
Key = {fds363089}
}
@article{fds356008,
Author = {Darden, M and Espie, CA and Carl, JR and Henry, AL and Kanady, JC and Krystal, AD and Miller, CB},
Title = {Cost-effectiveness of digital cognitive behavioral therapy
(Sleepio) for insomnia: a Markov simulation model in the
United States.},
Journal = {Sleep},
Volume = {44},
Number = {4},
Pages = {zsaa223},
Year = {2021},
Month = {April},
url = {http://dx.doi.org/10.1093/sleep/zsaa223},
Abstract = {STUDY OBJECTIVES: To examine the cost-effectiveness and
potential net monetary benefit (NMB) of a fully automated
digital cognitive behavioral therapy (CBT) intervention for
insomnia compared with no insomnia treatment in the United
States (US). Similar relative comparisons were made for
pharmacotherapy and clinician-delivered CBT (individual and
group). METHODS: We simulated a Markov model of 100,000
individuals using parameters calibrated from the literature
including direct (treatment) and indirect costs (e.g.
insomnia-related healthcare expenditure and lost workplace
productivity). Health utility estimates were converted into
quality-adjusted life years (QALYs) and one QALY was worth
$50,000. Simulated individuals were randomized equally to
one of five arms (digital CBT, pharmacotherapy, individual
CBT, group CBT, or no insomnia treatment). Sensitivity was
assessed by bootstrapping the calibrated parameters. Cost
estimates were expressed in 2019 US dollars. RESULTS:
Digital CBT was cost beneficial when compared with no
insomnia treatment and had a positive NMB of $681.06 (per
individual over 6 months). Bootstrap sensitivity analysis
demonstrated that the NMB was positive in 94.7% of
simulations. Relative to other insomnia treatments, digital
CBT was the most cost-effective treatment because it
generated the smallest incremental cost-effectiveness ratio
(-$3,124.73). CONCLUSIONS: Digital CBT was the most
cost-effective insomnia treatment followed by group CBT,
pharmacotherapy, and individual CBT. It is financially
prudent and beneficial from a societal perspective to
utilize automated digital CBT to treat insomnia at a
population scale.},
Doi = {10.1093/sleep/zsaa223},
Key = {fds356008}
}
@article{fds357354,
Author = {Ohayon, MM and McCue, M and Krystal, A and Chrones, L and Touya, M and Lawrence, D and Patel, S and Cote, ML},
Title = {A Longitudinal Study to Assess Antidepressant Treatment
Patterns and Outcomes in Individuals with Depression in the
General Population.},
Journal = {Cns Spectrums},
Volume = {26},
Number = {2},
Pages = {180},
Year = {2021},
Month = {April},
url = {http://dx.doi.org/10.1017/S1092852920002965},
Abstract = {STUDY OBJECTIVES: Depression is an important cause of
disability in the United States (US). The care experience of
major depressive disorder (MDD) is highly variable and has
only been documented to a limited degree. This study
examines the prevalence incidence and treatment patterns for
MDD in the US general population. METHODS: In this
longitudinal study 2 interview waves were conducted between
2002 and 2015. The initial wave (W1) was carried out with
12,218 individuals from the general population in 8 US
states with participants aged 18 years or older. In the
second wave (W2) 10,931 of the initial participants agreed
to be interviewed again 3 years later; the analyses were
carried out for individuals who participated in both
interviews (N=10,931). Diagnosis of MDD was confirmed
according to Diagnostic and Statistical Manual of Mental
Disorders Fifth Edition (DSM-5) criteria. RESULTS: The
3-year incidence of MDD was 3.4% (95% CI 3.1%-3.7%). The
prevalence of MDD was 5.1% (95% CI 4.7%-5.5%) and 4.2% (95%
CI 3.8%-4.6%) in W1 and W2, respectively. The percentages of
participants who achieved partial and complete remission
were 4.4% (95% CI 4.0%-4.8%) and 3.9% (95% CI 3.5%-4.3%) in
W1 compared with 7.9% (95% CI 7.4%-8.4%) and 4.4% (95% CI
4.0%-4.8%) in W2, respectively. The prevalence of MDD was
13.4% and 16.5% in W1 and W2, respectively, when including
participants with MDD partial and complete remission
episodes. 61.9% of participants with an MDD diagnosis in W1
had at least one associated comorbidity. 41.8% of
participants with an MDD diagnosis at W1 still reported
significant depressive symptoms at W2. 19.9% of participants
in partial remission and 5.5% of participants in complete
remission in W1 did not achieve remission in W2. 52.2% and
42.9% of participants with MDD were treated with an
antidepressant (AD) in W1 and W2, respectively; selective
serotonin reuptake inhibitors (SSRIs) were the most commonly
prescribed (34.7% in W1 vs 28.3% in W2). ADs were mainly
prescribed by primary care physicians (45.7%) followed by
psychiatrists (31.4%), neurologists (2.5%), and other
specialties (7.9%). The average duration of treatment was
36.9 (SE 2.4) months. More than one-third of AD users in W1
expressed dissatisfaction with their AD treatment which
translated into changes in types of antidepressant in W2.
CONCLUSION: Depression affects a sizable part of the general
population in the US with a prevalence of MDD at
13.4%-16.5%; yet MDD remains largely undertreated as shown
by the finding that only about half (52%) of individuals in
this study who met the diagnostic criteria for MDD were
treated with an antidepressant (SSRI being the most common
treatment). In addition, more than a quarter of patients
with MDD in this study did not achieve remission after
initial treatment underscoring the challenges in successful
antidepressant treatment of MDD. FUNDING: Takeda
Pharmaceuticals U.S.A. Inc. and Lundbeck
LLC.},
Doi = {10.1017/S1092852920002965},
Key = {fds357354}
}
@article{fds355261,
Author = {Scangos, KW and Makhoul, GS and Sugrue, LP and Chang, EF and Krystal,
AD},
Title = {State-dependent responses to intracranial brain stimulation
in a patient with depression.},
Journal = {Nat Med},
Volume = {27},
Number = {2},
Pages = {229-231},
Year = {2021},
Month = {February},
url = {http://dx.doi.org/10.1038/s41591-020-01175-8},
Abstract = {Deep brain stimulation is a promising treatment for severe
depression, but lack of efficacy in randomized trials raises
questions regarding anatomical targeting. We implanted
multi-site intracranial electrodes in a severely depressed
patient and systematically assessed the acute response to
focal electrical neuromodulation. We found an elaborate
repertoire of distinctive emotional responses that were
rapid in onset, reproducible, and context and state
dependent. Results provide proof of concept for
personalized, circuit-specific medicine in
psychiatry.},
Doi = {10.1038/s41591-020-01175-8},
Key = {fds355261}
}
@article{fds354762,
Author = {Lunsford-Avery, JR and Edinger, JD and Krystal,
AD},
Title = {Optimizing computation of overnight decline in delta power:
Evidence for slower rate of decline in delta power in
insomnia patients.},
Journal = {Clin Neurophysiol},
Volume = {132},
Number = {2},
Pages = {545-553},
Year = {2021},
Month = {February},
url = {http://dx.doi.org/10.1016/j.clinph.2020.12.004},
Abstract = {OBJECTIVE: To determine the best of commonly used methods
for computing the rate of decline in non-rapid eye movement
(NREM) sleep EEG delta power overnight (Delta Decline) in
terms of vulnerability to missing data and to evaluate
whether this rate is slower in insomnia patients than
healthy controls (HC). METHODS: Fifty-one insomnia patients
and 53 HC underwent 6 nights of polysomnography. Four
methods for estimating Delta Decline were compared
(exponential and linear best-fit functions using NREM (1)
episode mean, (2) peak, and (3) total delta power and (4)
delta power for all available NREM epochs). The best method
was applied to compare groups on linear and exponential
rates of Delta Decline. RESULTS: Best-fit models using all
available NREM epochs were significantly less vulnerable to
deviation due to missing data than other methods. Insomnia
patients displayed significantly slower linear and
exponential Delta Decline than HC. CONCLUSIONS: Computing
Delta Decline using all available NREM epochs was the best
of the methods studied for minimizing the effects of missing
data. Insomnia patients display slower Delta Decline, which
is not explained by differences in total sleep time or wake
after sleep onset. SIGNIFICANCE: This study supports using
all available NREM epochs in Delta Decline computation and
suggests a slower rate in insomnia.},
Doi = {10.1016/j.clinph.2020.12.004},
Key = {fds354762}
}
@article{fds353079,
Author = {Shi, G and Yin, C and Fan, Z and Xing, L and Mostovoy, Y and Kwok, P-Y and Ashbrook, LH and Krystal, AD and Ptáček, LJ and Fu,
Y-H},
Title = {Mutations in Metabotropic Glutamate Receptor 1 Contribute to
Natural Short Sleep Trait.},
Journal = {Curr Biol},
Volume = {31},
Number = {1},
Pages = {13-24.e4},
Year = {2021},
Month = {January},
url = {http://dx.doi.org/10.1016/j.cub.2020.09.071},
Abstract = {Sufficient and efficient sleep is crucial for our health.
Natural short sleepers can sleep significantly shorter than
the average population without a desire for more sleep and
without any obvious negative health consequences. In
searching for genetic variants underlying the short sleep
trait, we found two different mutations in the same gene
(metabotropic glutamate receptor 1) from two independent
natural short sleep families. In vitro, both of the
mutations exhibited loss of function in receptor-mediated
signaling. In vivo, the mice carrying the individual
mutations both demonstrated short sleep behavior. In brain
slices, both of the mutations changed the electrical
properties and increased excitatory synaptic transmission.
These results highlight the important role of metabotropic
glutamate receptor 1 in modulating sleep
duration.},
Doi = {10.1016/j.cub.2020.09.071},
Key = {fds353079}
}
@article{fds352459,
Author = {McCall, WV and Benca, RM and Rumble, ME and Krystal,
AD},
Title = {Blinding and bias in a hypnotic clinical
trial.},
Journal = {Hum Psychopharmacol},
Volume = {36},
Number = {1},
Pages = {1-5},
Year = {2021},
Month = {January},
url = {http://dx.doi.org/10.1002/hup.2757},
Abstract = {OBJECTIVES: Information is lacking regarding how commonly
unblinding of treatment assignment occurs in hypnotic
randomized clinic trials (RCTs). We now report the "best
guesses" of clinical trial participants, versus study
coordinators, versus study physicians in the study Reducing
Suicidal Ideation Through Insomnia Treatment (REST-IT).
METHODS: REST-IT, a, 8-week double-blind RCT, compared
zolpidem extended-release (ER) versus placebo at bedtime in
103 adults with major depressive disorder with insomnia and
suicidal ideation, and who received open label selective
serotonin reuptake inhibitors. At the conclusion of study
participation, 89 of the participants in this study, the
study coordinators, and the study physicians each
independently recorded their "best guess" of the treatment
assigned. RESULTS: Patients guessed correctly 58.4% of the
time, coordinators 53.9% of the time, and physicians 49.4%
of the time, and none were different from chance alone.
Agreement between patient/coordinator, patient/doctor, and
coordinator/doctor dyads were 75%-78% with no significant
differences in agreement between the dyads. CONCLUSIONS:
"Best guesses" of all parties were not different from
chance, suggesting that the blind was maintained and that
assessment bias was minimized in this RCT of zolpidem ER
versus placebo. Our results may not apply to other hypnotics
or other RCT designs.},
Doi = {10.1002/hup.2757},
Key = {fds352459}
}
@article{fds352460,
Author = {Krystal, AD and Mittoux, A and Lindsten, A and Baker,
RA},
Title = {Chronobiologic parameter changes in patients with major
depressive disorder and sleep disturbance treated with
adjunctive brexpiprazole: An open-label, flexible-dose,
exploratory substudy.},
Journal = {J Affect Disord},
Volume = {278},
Pages = {288-295},
Year = {2021},
Month = {January},
url = {http://dx.doi.org/10.1016/j.jad.2020.09.026},
Abstract = {BACKGROUND: Circadian rhythm disturbances have been reported
in patients with major depressive disorder (MDD). Among
these is an increased phase angle between peak cortisol
concentration and dim-light melatonin onset (DLMO). The aim
of this study was to evaluate changes in chronobiologic
parameters of sleep in patients with MDD receiving
adjunctive brexpiprazole. METHODS: This was an
interventional, multicenter, open-label, flexible-dose,
exploratory study in patients with MDD and inadequate
response to antidepressant treatment who were experiencing
sleep disturbances. Patients received adjunctive
brexpiprazole 2-3 mg/day for 8 weeks. Outcome measures
included cortisol and melatonin levels, used to calculate
phase angle, and the Biological Rhythms Interview of
Assessment in Neuropsychiatry (BRIAN). RESULTS: The mean
(standard error) phase angle between peak cortisol and DLMO
increased by 108 (61) minutes from baseline to Week 8
(n = 9). BRIAN Total score changed (improved) by -14.6
(4.6) points from baseline to Week 8 (n = 9). Change in
phase angle and BRIAN Total score showed a moderate-to-high
correlation (Pearson coefficient: 0.68; 95% confidence
limits: 0.04, 0.93; p = 0.040). LIMITATIONS: This study
is limited by its small sample size, and its single-arm,
open-label design. CONCLUSIONS: The findings provide a
preliminary indication that the phase angle between peak
cortisol and DLMO is of interest as a potential biomarker
for depression and therapeutic response. Adjunctive
brexpiprazole may represent a strategy for correcting
circadian dysfunction in patients with MDD and inadequate
response to antidepressant treatment. ClinicalTrials.gov
identifier: NCT01942733.},
Doi = {10.1016/j.jad.2020.09.026},
Key = {fds352460}
}
@article{fds359853,
Author = {Scangos, KW and Khambhati, AN and Daly, PM and Owen, LW and Manning, JR and Ambrose, JB and Austin, E and Dawes, HE and Krystal, AD and Chang,
EF},
Title = {Distributed Subnetworks of Depression Defined by Direct
Intracranial Neurophysiology.},
Journal = {Frontiers in Human Neuroscience},
Volume = {15},
Pages = {746499},
Year = {2021},
url = {http://dx.doi.org/10.3389/fnhum.2021.746499},
Abstract = {Major depressive disorder is a common and disabling disorder
with high rates of treatment resistance. Evidence suggests
it is characterized by distributed network dysfunction that
may be variable across patients, challenging the
identification of quantitative biological substrates. We
carried out this study to determine whether application of a
novel computational approach to a large sample of high
spatiotemporal resolution direct neural recordings in humans
could unlock the functional organization and coordinated
activity patterns of depression networks. This group level
analysis of depression networks from heterogenous
intracranial recordings was possible due to application of a
correlational model-based method for inferring whole-brain
neural activity. We then applied a network framework to
discover brain dynamics across this model that could
classify depression. We found a highly distributed pattern
of neural activity and connectivity across cortical and
subcortical structures that was present in the majority of
depressed subjects. Furthermore, we found that this
depression signature consisted of two subnetworks across
individuals. The first was characterized by left temporal
lobe hypoconnectivity and pathological beta activity. The
second was characterized by a hypoactive, but hyperconnected
left frontal cortex. These findings have applications toward
personalization of therapy.},
Doi = {10.3389/fnhum.2021.746499},
Key = {fds359853}
}
@article{fds349964,
Author = {Hatch, GM and Ashbrook, L and Prather, AA and Krystal,
AD},
Title = {Is cellular energy monitoring more responsive to hypoxia
than pulse oximetry?},
Journal = {Sleep Breath},
Volume = {24},
Number = {4},
Pages = {1633-1643},
Year = {2020},
Month = {December},
url = {http://dx.doi.org/10.1007/s11325-020-02104-2},
Abstract = {PURPOSE: Pulse oximetry is the current standard for
detecting drops in arterial blood oxygen saturation (SpO2)
associated with obstructive sleep apnea and hypopnea events
in polysomnographic (PSG) testing. However, cellular energy
monitoring (CE monitoring), a measure related to cellular
hypoxia in the skin, is likely to be more responsive to
inadequate breathing during sleep because during hypoxic
challenge, such as occurs during apneic events, regulatory
mechanisms restrict blood flow to the skin to preferentially
maintain SpO2 for more vital organs. We carried out initial
proof of concept testing to determine if CE monitoring has
promise for being more responsive to hypoxic challenge
occurring during sleep-disordered breathing (SDB) than pulse
oximetry. METHODS: We assessed both CE monitoring and pulse
oximetry in a series of conditions which affect oxygen
supply: (1) breathing nitrogen or 100% oxygen, (2) physical
exertion, and (3) studying a night of sleep in an individual
known to be a loud snorer. We also present the results of a
preliminary study comparing CE monitoring to pulse oximetry
in eight individuals undergoing standard clinical overnight
polysomnography for suspected SDB. RESULTS: CE monitoring is
responsive to changes in cellular oxygen supply to the skin
and detects hypoxia during SDB events that is not detected
by pulse oximetry. CONCLUSION: CE monitoring is a promising
tool for identifying pathology at the mild end of the SDB
spectrum.},
Doi = {10.1007/s11325-020-02104-2},
Key = {fds349964}
}
@article{fds353859,
Author = {Dias-Barbosa, C and Matos, R and Vernon, M and Carney, CE and Krystal,
A and Puelles, J},
Title = {Content validity of a sleep numerical rating scale and a
sleep diary in adults and adolescents with
moderate-to-severe atopic dermatitis},
Journal = {Journal of Patient Reported Outcomes},
Volume = {4},
Number = {1},
Year = {2020},
Month = {December},
url = {http://dx.doi.org/10.1186/s41687-020-00265-y},
Abstract = {Background: The intense itching associated with atopic
dermatitis (AD) often causes patients to experience severe
sleep disturbance. Here, we describe the results of a
two-phase concept elicitation and cognitive interview study
to establish the content validity of a sleep disturbance
numerical rating scale (SD NRS) and a Consensus Sleep Diary
adapted for adults and adolescents with moderate-to-severe
AD (CSD-AD©). Results: In phase I, a concept elicitation
conducted in 20 adults and 10 adolescents with
moderate-to-severe AD revealed that the following
sleep-related issues were important and relevant: nighttime
awakening (87%), trouble falling asleep (73%), feeling
unrested (53%), daytime fatigue or sleepiness (53%), and
feeling as if they did not get enough sleep (33%). The
frequency and extent of sleep disturbance varied
substantially from day to day due to varying degrees of
itching and flares, medication use, and changes in the
weather. All participants understood the SD NRS question,
with most finding it easy or very easy to understand (100%
of adults and 90% of adolescents) and most understanding the
anchors as intended (95% of adults, and 100% of
adolescents). Most participants (94% of adults, and 90% of
adolescents) indicated that they would consider a one- or
two-point change meaningful on the SD NRS. The CSD-AD© was
revised based on participant feedback, and tested during
phase II in a convenience sample of six adults and four
adolescents from phase I. The changes made to the CSD-AD©
were confirmed to be relevant and understandable. All
patients were able to provide an answer to each item in the
CSD-AD©, and most were able to estimate the duration of
nighttime awakenings, daytime naps, and dozing. Conclusions:
The study supported the content validity of the SD NRS and
CSD-AD© in adults and adolescents with moderate-to-severe
AD. It also emphasized the importance of using these
instruments daily when assessing the benefit of a new
treatment on sleep quality in this population.},
Doi = {10.1186/s41687-020-00265-y},
Key = {fds353859}
}
@article{fds354561,
Author = {Dias-Barbosa, C and Matos, R and Vernon, M and Carney, CE and Krystal,
A and Puelles, J},
Title = {Correction to: Content validity of a sleep numerical rating
scale and a sleep diary in adults and adolescents with
moderate-to-severe atopic dermatitis (Journal of
Patient-Reported Outcomes, (2020), 4, 1, (100),
10.1186/s41687-020-00265-y)},
Journal = {Journal of Patient Reported Outcomes},
Volume = {4},
Number = {1},
Year = {2020},
Month = {December},
url = {http://dx.doi.org/10.1186/s41687-020-00279-6},
Abstract = {Following publication of the original article [1], the
authors identified an error in the listed corresponding
author. She should be identified as Carla Dias-Barbosa and
not as Rodolfo Matos.},
Doi = {10.1186/s41687-020-00279-6},
Key = {fds354561}
}
@article{fds350882,
Author = {Morin, CM and Edinger, JD and Beaulieu-Bonneau, S and Ivers, H and Krystal, AD and Guay, B and Bélanger, L and Cartwright, A and Simmons,
B and Lamy, M and Busby, M},
Title = {Effectiveness of Sequential Psychological and Medication
Therapies for Insomnia Disorder: A Randomized Clinical
Trial.},
Journal = {Jama Psychiatry},
Volume = {77},
Number = {11},
Pages = {1107-1115},
Year = {2020},
Month = {November},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2020.1767},
Abstract = {IMPORTANCE: Despite evidence of efficacious psychological
and pharmacologic therapies for insomnia, there is little
information about what first-line treatment should be and
how best to proceed when initial treatment fails. OBJECTIVE:
To evaluate the comparative efficacy of 4 treatment
sequences involving psychological and medication therapies
for insomnia and examine the moderating effect of
psychiatric disorders on insomnia outcomes. DESIGN, SETTING,
AND PARTICIPANTS: In a sequential multiple-assignment
randomized trial, patients were assigned to first-stage
therapy involving either behavioral therapy (BT;
n = 104) or zolpidem (zolpidem; n = 107), and
patients who did not remit received a second treatment
involving either medication (zolpidem or trazodone) or
psychological therapy (BT or cognitive therapy [CT]). The
study took place at Institut Universitaire en Santé Mentale
de Québec, Université Laval, Québec City, Québec,
Canada, and at National Jewish Health, Denver, Colorado, and
enrollment of patients took place from August 2012 through
July 2017. MAIN OUTCOMES AND MEASURES: The primary end
points were the treatment response and remission rates,
defined by the Insomnia Severity Index total score. RESULTS:
Patients included 211 adults (132 women; mean [SD] age, 45.6
[14.9] years) with a chronic insomnia disorder, including 74
patients with a comorbid anxiety or mood disorder.
First-stage therapy with BT or zolpidem produced equivalent
weighted percentages of responders (BT, 45.5%; zolpidem,
49.7%; OR, 1.18; 95% CI, 0.60-2.33) and remitters (BT,
38.03%; zolpidem, 30.3%; OR, 1.41; 95% CI, 0.75-2.65).
Second-stage therapy produced significant increases in
responders for the 2 conditions, starting with BT (BT to
zolpidem, 40.6% to 62.7%; OR, 2.46; 95% CI, 1.14-5.30; BT to
CT, 50.1% to 68.2%; OR, 2.09; 95% CI, 1.01-4.35) but no
significant change following zolpidem treatment. Significant
increase in percentage of remitters was observed in 2 of 4
therapy sequences (BT to zolpidem, 38.1% to 55.9%; OR, 2.06;
95% CI, 1.04-4.11; zolpidem to trazodone, 31.4% to 49.4%;
OR, 2.13; 95% CI, 0.91-5.00). Although response/remission
rates were lower among patients with psychiatric
comorbidity, treatment sequences that involved BT followed
by CT or zolpidem followed by trazodone yielded better
outcomes for patients with comorbid insomnia. Response and
remission rates were well sustained through the 12-month
follow-up. CONCLUSIONS AND RELEVANCE: Behavioral therapy and
zolpidem medication produced equivalent response and
remission rates. Adding a second treatment produced an added
value for those whose insomnia failed to remit with initial
therapies. TRIAL REGISTRATION: ClinicalTrials.gov
Identifier: NCT01651442.},
Doi = {10.1001/jamapsychiatry.2020.1767},
Key = {fds350882}
}
@article{fds352847,
Author = {Lunsford-Avery, JR and Keller, C and Kollins, SH and Krystal, AD and Jackson, L and Engelhard, MM},
Title = {Feasibility and Acceptability of Wearable Sleep
Electroencephalogram Device Use in Adolescents:
Observational Study.},
Journal = {Jmir Mhealth and Uhealth},
Volume = {8},
Number = {10},
Pages = {e20590},
Year = {2020},
Month = {October},
url = {http://dx.doi.org/10.2196/20590},
Abstract = {BACKGROUND: Adolescence is an important life stage for the
development of healthy behaviors, which have a long-lasting
impact on health across the lifespan. Sleep undergoes
significant changes during adolescence and is linked to
physical and psychiatric health; however, sleep is rarely
assessed in routine health care settings. Wearable sleep
electroencephalogram (EEG) devices may represent
user-friendly methods for assessing sleep among adolescents,
but no studies to date have examined the feasibility and
acceptability of sleep EEG wearables in this age group.
OBJECTIVE: The goal of the research was to investigate the
feasibility and acceptability of sleep EEG wearable devices
among adolescents aged 11 to 17 years. METHODS: A total of
104 adolescents aged 11 to 17 years participated in 7 days
of at-home sleep recording using a self-administered
wearable sleep EEG device (Zmachine Insight+, General Sleep
Corporation) as well as a wristworn actigraph. Feasibility
was assessed as the number of full nights of successful
recording completed by adolescents, and acceptability was
measured by the wearable acceptability survey for sleep.
Feasibility and acceptability were assessed separately for
the sleep EEG device and wristworn actigraph. RESULTS: A
total of 94.2% (98/104) of adolescents successfully recorded
at least 1 night of data using the sleep EEG device (mean
number of nights 5.42; SD 1.71; median 6, mode 7). A total
of 81.6% (84/103) rated the comfort of the device as falling
in the comfortable to mildly uncomfortable range while
awake. A total of 40.8% (42/103) reported typical sleep
while using the device, while 39.8% (41/103) indicated
minimal to mild device-related sleep disturbances. A
minority (32/104, 30.8%) indicated changes in their sleep
position due to device use, and very few (11/103, 10.7%)
expressed dissatisfaction with their experience with the
device. A similar pattern was observed for the wristworn
actigraph device. CONCLUSIONS: Wearable sleep EEG appears to
represent a feasible, acceptable method for sleep assessment
among adolescents and may have utility for assessing and
treating sleep disturbances at a population level. Future
studies with adolescents should evaluate strategies for
further improving usability of such devices, assess
relationships between sleep EEG-derived metrics and health
outcomes, and investigate methods for incorporating data
from these devices into emerging digital interventions and
applications. TRIAL REGISTRATION: ClinicalTrials.gov
NCT03843762; https://clinicaltrials.gov/ct2/show/NCT03843762.},
Doi = {10.2196/20590},
Key = {fds352847}
}
@article{fds351454,
Author = {Pizzagalli, DA and Smoski, M and Ang, Y-S and Whitton, AE and Sanacora,
G and Mathew, SJ and Nurnberger, J and Lisanby, SH and Iosifescu, DV and Murrough, JW and Yang, H and Weiner, RD and Calabrese, JR and Goodman,
W and Potter, WZ and Krystal, AD},
Title = {Selective kappa-opioid antagonism ameliorates anhedonic
behavior: evidence from the Fast-fail Trial in Mood and
Anxiety Spectrum Disorders (FAST-MAS).},
Journal = {Neuropsychopharmacology},
Volume = {45},
Number = {10},
Pages = {1656-1663},
Year = {2020},
Month = {September},
url = {http://dx.doi.org/10.1038/s41386-020-0738-4},
Abstract = {Anhedonia remains a major clinical issue for which there is
few effective interventions. Untreated or poorly controlled
anhedonia has been linked to worse disease course and
increased suicidal behavior across disorders. Taking a
proof-of-mechanism approach under the auspices of the
National Institute of Mental Health FAST-FAIL initiative, we
were the first to show that, in a transdiagnostic sample
screened for elevated self-reported anhedonia, 8 weeks of
treatment with a kappa-opioid receptor (KOR) antagonist
resulted in significantly higher reward-related activation
in one of the core hubs of the brain reward system (the
ventral striatum), better reward learning in the
Probabilistic Reward Task (PRT), and lower anhedonic
symptoms, relative to 8 weeks of placebo. Here, we performed
secondary analyses of the PRT data to investigate the
putative effects of KOR antagonism on anhedonic behavior
with more precision by using trial-level model-based
Bayesian computational modeling and probability analyses. We
found that, relative to placebo, KOR antagonism resulted in
significantly higher learning rate (i.e., ability to learn
from reward feedback) and a more sustained preference toward
the more frequently rewarded stimulus, but unaltered reward
sensitivity (i.e., the hedonic response to reward feedback).
Collectively, these findings provide novel evidence that in
a transdiagnostic sample characterized by elevated
anhedonia, KOR antagonism improved the ability to modulate
behavior as a function of prior rewards. Together with
confirmation of target engagement in the primary report
(Krystal et al., Nat Med, 2020), the current findings
suggest that further transdiagnostic investigation of KOR
antagonism for anhedonia is warranted.},
Doi = {10.1038/s41386-020-0738-4},
Key = {fds351454}
}
@article{fds351508,
Author = {Rumble, ME and McCall, WV and Dickson, DA and Krystal, AD and Rosenquist, PB and Benca, RM},
Title = {An exploratory analysis of the association of circadian
rhythm dysregulation and insomnia with suicidal ideation
over the course of treatment in individuals with depression,
insomnia, and suicidal ideation.},
Journal = {J Clin Sleep Med},
Volume = {16},
Number = {8},
Pages = {1311-1319},
Year = {2020},
Month = {August},
url = {http://dx.doi.org/10.5664/jcsm.8508},
Abstract = {STUDY OBJECTIVES: Sleep disturbance is significantly
associated with suicidal ideation. However, the majority of
past research has examined the relationship between insomnia
and suicidality. The current exploratory study examined the
relationship of circadian rhythm dysregulation (eveningness,
seasonality, and rhythmicity) with suicidality. METHODS: We
examined the association of insomnia, eveningness,
seasonality, and rhythmicity with suicidal ideation in 103
participants with depression, insomnia, and suicidality
within a larger 8-week double-blinded randomized control
trial primarily examining whether cautious use of zolpidem
extended-release or placebo reduced suicidal ideation. All
participants additionally received an open-label selective
serotonin reuptake inhibitor. Methodological strengths of
the current analyses included consideration of multiple
sleep-wake constructs, adjustment for relevant covariates,
investigation of relationships over the course of treatment,
and use of both self-report measures and objective
measurement with actigraphy. RESULTS: Over the course of
treatment, self-reported eveningness and greater insomnia
severity were independently correlated with greater suicidal
ideation, whereas actigraphic delayed sleep timing was
related to suicidal ideation at a trend level. At the end of
treatment, those with greater suicidal ideation demonstrated
lower actigraphic activity levels. There were no significant
relationships between self-reported seasonality and
actigraphic measures of sleep disturbance and suicidality.
CONCLUSIONS: Self-reported delays in sleep timing,
objectively lower activity levels, and self-reported
insomnia severity correlated independently with greater
suicidal ideation in those with depression, insomnia, and
suicidality. These exploratory findings highlight the need
to consider sleep-wake constructs more broadly in those with
suicidality in future research studies in order to improve
more definitively both assessment and intervention efforts.
CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov;
Name: Reducing Suicidal Ideation through Insomnia Treatment;
URL: https://clinicaltrials.gov/ct2/show/NCT01689909;
Identifier: NCT01689909 Rumble ME, McCall MV, Dickson DA,
Krystal AD, Rosenquist PB, Benca RM. An exploratory analysis
of the association of circadian rhythm dysregulation and
insomnia with suicidal ideation over the course of treatment
in individuals with depression, insomnia, and suicidal
ideation. J Clin Sleep Med. 2020;16(8):XXX-XXX.},
Doi = {10.5664/jcsm.8508},
Key = {fds351508}
}
@article{fds349554,
Author = {Krystal, AD},
Title = {Omitted Conflict of Interest Disclosures.},
Journal = {Jama Psychiatry},
Volume = {77},
Number = {7},
Pages = {768},
Year = {2020},
Month = {July},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2020.0616},
Doi = {10.1001/jamapsychiatry.2020.0616},
Key = {fds349554}
}
@article{fds365986,
Author = {Lunsford-Avery, JR and Keller, C and Kollins, SH and Krystal, AD and Jackson, L and Engelhard, MM},
Title = {Feasibility and Acceptability of Wearable Sleep
Electroencephalogram Device Use in Adolescents:
Observational Study (Preprint)},
Year = {2020},
Month = {May},
url = {http://dx.doi.org/10.2196/preprints.20590},
Abstract = {<sec> <title>BACKGROUND</title> <p>Adolescence is an
important life stage for the development of healthy
behaviors, which have a long-lasting impact on health across
the lifespan. Sleep undergoes significant changes during
adolescence and is linked to physical and psychiatric
health; however, sleep is rarely assessed in routine health
care settings. Wearable sleep electroencephalogram (EEG)
devices may represent user-friendly methods for assessing
sleep among adolescents, but no studies to date have
examined the feasibility and acceptability of sleep EEG
wearables in this age group.</p> </sec> <sec>
<title>OBJECTIVE</title> <p>The goal of the research was to
investigate the feasibility and acceptability of sleep EEG
wearable devices among adolescents aged 11 to 17 years.</p>
</sec> <sec> <title>METHODS</title> <p>A total of 104
adolescents aged 11 to 17 years participated in 7 days of
at-home sleep recording using a self-administered wearable
sleep EEG device (Zmachine Insight+, General Sleep
Corporation) as well as a wristworn actigraph. Feasibility
was assessed as the number of full nights of successful
recording completed by adolescents, and acceptability was
measured by the wearable acceptability survey for sleep.
Feasibility and acceptability were assessed separately for
the sleep EEG device and wristworn actigraph.</p> </sec>
<sec> <title>RESULTS</title> <p>A total of 94.2% (98/104) of
adolescents successfully recorded at least 1 night of data
using the sleep EEG device (mean number of nights 5.42; SD
1.71; median 6, mode 7). A total of 81.6% (84/103) rated the
comfort of the device as falling in the comfortable to
mildly uncomfortable range while awake. A total of 40.8%
(42/103) reported typical sleep while using the device,
while 39.8% (41/103) indicated minimal to mild
device-related sleep disturbances. A minority (32/104,
30.8%) indicated changes in their sleep position due to
device use, and very few (11/103, 10.7%) expressed
dissatisfaction with their experience with the device. A
similar pattern was observed for the wristworn actigraph
device.</p> </sec> <sec> <title>CONCLUSIONS</title>
<p>Wearable sleep EEG appears to represent a feasible,
acceptable method for sleep assessment among adolescents and
may have utility for assessing and treating sleep
disturbances at a population level. Future studies with
adolescents should evaluate strategies for further improving
usability of such devices, assess relationships between
sleep EEG–derived metrics and health outcomes, and
investigate methods for incorporating data from these
devices into emerging digital interventions and
applications.</p> </sec> <sec> <title>CLINICALTRIAL</title>
<p>ClinicalTrials.gov NCT03843762; https://clinicaltrials.gov/ct2/show/NCT03843762</p>
</sec>},
Doi = {10.2196/preprints.20590},
Key = {fds365986}
}
@article{fds349367,
Author = {Krystal, AD and Pizzagalli, DA and Smoski, M and Mathew, SJ and Nurnberger, J and Lisanby, SH and Iosifescu, D and Murrough, JW and Yang, H and Weiner, RD and Calabrese, JR and Sanacora, G and Hermes, G and Keefe, RSE and Song, A and Goodman, W and Szabo, ST and Whitton, AE and Gao, K and Potter, WZ},
Title = {A randomized proof-of-mechanism trial applying the
'fast-fail' approach to evaluating κ-opioid antagonism as a
treatment for anhedonia.},
Journal = {Nat Med},
Volume = {26},
Number = {5},
Pages = {760-768},
Year = {2020},
Month = {May},
url = {http://dx.doi.org/10.1038/s41591-020-0806-7},
Abstract = {The National Institute of Mental Health (NIMH) 'fast-fail'
approach seeks to improve too-often-misleading early-phase
drug development methods by incorporating biomarker-based
proof-of-mechanism (POM) testing in phase 2a. This first
comprehensive application of the fast-fail approach
evaluated the potential of κ-opioid receptor (KOR)
antagonism for treating anhedonia with a POM study
determining whether robust target engagement favorably
impacts the brain circuitry hypothesized to mediate clinical
effects. Here we report the results from a multicenter,
8-week, double-blind, placebo-controlled, randomized trial
in patients with anhedonia and a mood or anxiety disorder
(selective KOR antagonist (JNJ-67953964, 10 mg;
n = 45) and placebo (n = 44)). JNJ-67953964
significantly increased functional magnetic resonance
imaging (fMRI) ventral striatum activation during reward
anticipation (primary outcome) as compared to placebo
(baseline-adjusted mean: JNJ-67953964, 0.72
(s.d. = 0.67); placebo, 0.33 (s.d. = 0.68);
F(1,86) = 5.58, P < 0.01; effect size = 0.58
(95% confidence interval, 0.13-0.99)). JNJ-67953964,
generally well tolerated, was not associated with any
serious adverse events. This study supports proceeding with
assessment of the clinical impact of target engagement and
serves as a model for implementing the 'fast-fail'
approach.},
Doi = {10.1038/s41591-020-0806-7},
Key = {fds349367}
}
@article{fds366469,
Author = {Felder, JN and Epel, ES and Neuhaus, J and Krystal, AD and Prather,
AA},
Title = {Efficacy of Digital Cognitive Behavioral Therapy for the
Treatment of Insomnia Symptoms Among Pregnant Women: A
Randomized Clinical Trial.},
Journal = {Jama Psychiatry},
Volume = {77},
Number = {5},
Pages = {484-492},
Year = {2020},
Month = {May},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2019.4491},
Abstract = {IMPORTANCE: Despite the prevalence and adverse consequences
of prenatal insomnia, a paucity of research is available
regarding interventions to improve insomnia symptoms during
pregnancy. OBJECTIVE: To test the efficacy of digital
cognitive behavioral therapy for insomnia (CBT-I) compared
with standard treatment among pregnant women with insomnia
symptoms. DESIGN, SETTING, AND PARTICIPANTS: This randomized
clinical trial enrolled pregnant women from November 23,
2016, to May 22, 2018. Of the 2258 women assessed for
eligibility using an online self-report questionnaire, 208
were randomized to receive digital CBT-I (n = 105) or
standard treatment (n = 103) for insomnia. Participants
were pregnant up to 28 weeks' gestation, and they either had
elevated insomnia symptom severity or met the criteria for
insomnia caseness as determined by self-report
questionnaires. Participants completed outcome measures at
10 weeks (postintervention) and 18 weeks (follow-up) after
randomization. All study visits were completed remotely, and
the intervention was delivered digitally. Data were analyzed
between December 12, 2018, and July 2, 2019. INTERVENTIONS:
Digital CBT-I consisted of 6 weekly sessions of
approximately 20 minutes each. Standard treatment reflected
standard care. Women receiving standard treatment had no
limits placed on the receipt of nonstudy treatments,
including medication and psychotherapy. MAIN OUTCOMES AND
MEASURES: All outcomes were assessed remotely using
self-report questionnaires administered via online survey.
The primary outcome was the change in insomnia symptom
severity (measured by the Insomnia Severity Index) from
baseline to postintervention. Secondary outcomes were sleep
efficiency and nightly sleep duration (defined by sleep
diary), global sleep quality (measured by the Pittsburgh
Sleep Quality Index), depressive symptom severity (measured
by the Edinburgh Postnatal Depression Scale), and anxiety
symptom severity (measured by the Generalized Anxiety
Disorder Scale-7). For each outcome, we also examined the
change from baseline to follow-up. RESULTS: The 208
participants had a mean (SD) age of 33.6 (3.7) years and a
mean (SD) gestational age of 17.6 (6.3) weeks at baseline.
Most of the participants were white (138 [66.3%]), married
or cohabiting (196 [94.2%]), had a college degree (180
[86.5%]), and earned $100 000 or more per year (141
[67.8%]). Women randomized to receive digital CBT-I
experienced statistically significantly greater improvements
in insomnia symptom severity from baseline to
postintervention compared with women randomized to receive
standard treatment (time-by-group interaction,
difference = -0.36; 95% CI, -0.48 to -0.23;
χ2 = 29.8; P < .001; d = -1.03). Improvements
from baseline to postintervention for all secondary
outcomes, with the exception of sleep duration, were
statistically significant. A similar pattern of results was
evident for the change from baseline to follow-up.
CONCLUSIONS AND RELEVANCE: In this trial, digital CBT was an
effective, scalable, safe, and acceptable intervention for
improving insomnia symptoms during pregnancy. TRIAL
REGISTRATION: ClinicalTrials.gov identifier:
NCT02805998.},
Doi = {10.1001/jamapsychiatry.2019.4491},
Key = {fds366469}
}
@article{fds349673,
Author = {Aluisio, L and Yieh, L and Wajs, E and DiBernardo, A and Krystal, A and Drevets, W and Wu, Y and Gogate, J and Daly, E and Zannikos, P and Curran,
V and Chen, G and Singh, J},
Title = {142 Withdrawal Symptom Assessment in an Esketamine Safety
Study in Patients with Treatment-resistant
Depression.},
Journal = {Cns Spectrums},
Volume = {25},
Number = {2},
Pages = {290},
Year = {2020},
Month = {April},
url = {http://dx.doi.org/10.1017/s1092852920000589},
Abstract = {BACKGROUND:SUSTAIN-2 (NCT02497287) was an open-label, phase
III trial evaluating the safety of esketamine (ESK) nasal
spray plus a newly initiated oral antidepressant (AD) for up
to 1 year in adults with treatment-resistant depression
(TRD). ESK is a schedule III drug that acts via glutamate
receptor modulation. ESK is rapidly cleared from the plasma,
and with intermittent dosing there is no accumulation. Thus,
no withdrawal syndrome is expected. The current analysis
assessed potential withdrawal symptoms in patients who
discontinued ESK after long-term, intermittent use. In the
absence of a glutamatergic-specific withdrawal scale, the
Physicians Withdrawal Checklist1 (PWC-20) was used. The
PWC-20 was designed to assess new or worsening
benzodiazepine-like discontinuation symptoms after stopping
non-SSRI anxiolytics. METHODS:ESK nasal spray was
administered two times per week during a 4-week induction
phase (IND). Responders entered the optimization/maintenance
phase (O/M) where ESK nasal spray was dosed either weekly or
every two weeks for up to 48 weeks. Patients entered a
4-week follow up period (F/U) after discontinuation from
either phase, during which continuation of the AD was
recommended. PWC-20 assessments were conducted at the last
ESK dosing (endpoint of IND or O/M) and at weeks 1, 2 and 4
of F/U. Symptoms were rated using a 0-3-point scale (Not
present = 0, Mild = 1, Moderate = 2, Severe = 3). To account
for worsening of underlying depression, subset calculations
were performed for depressive symptoms (PWC-DS: loss of
appetite; anxiety or nervousness; irritability; dysphoric
mood or depression; insomnia; fatigue, lethargy or lack of
energy; restlessness or agitation; headaches; muscle aches
or stiffness; weakness; difficulty concentrating or
remembering; depersonalization-derealization) and withdrawal
symptoms (PWC-WS: nausea and/or vomiting; diarrhea; poor
coordination; diaphoresis; tremor or tremulousness;
dizziness or light-headedness; increased acuity of sound,
smell, or touch; paresthesias). RESULTS:Data on 357 patients
entering F/U were included in the analysis (91 completed
treatment during the IND phase and 141 were treated during
O/M). The mean (SD) PWC-20 total scores (range 0-60) at
treatment endpoint, Week 1, 2 and 4 were 7.2 (6.8),
7.5(7.0), 7.4 (7.1) and 7.2 (6.9), respectively. At these
same assessment times, mean PWC-WS scores (range 0-24) were
0.9 (1.7), 1.0 (1.7), 1.0 (1.8), and 0.9 (1.8). Mean PWC-DS
scores (range 0-36) were 6.3 (5.6), 6.5 (5.7), 6.5 (5.8),
and 6.3 (5.7), respectively. Complete analysis of data from
the entire SUSTAIN-2 dataset will be presented.
CONCLUSIONS:No indication of drug-specific withdrawal
symptoms was seen after stopping up to 1-year of
intermittent treatment with ESK nasal spray for TRD. FUNDING
ACKNOWLEDGEMENTS:Janssen Research and Development.},
Doi = {10.1017/s1092852920000589},
Key = {fds349673}
}
@article{fds345926,
Author = {Ashbrook, LH and Krystal, AD and Fu, Y-H and Ptáček,
LJ},
Title = {Genetics of the human circadian clock and sleep
homeostat.},
Journal = {Neuropsychopharmacology},
Volume = {45},
Number = {1},
Pages = {45-54},
Year = {2020},
Month = {January},
url = {http://dx.doi.org/10.1038/s41386-019-0476-7},
Abstract = {Timing and duration of sleep are controlled by the circadian
system, which keeps an ~24-h internal rhythm that entrains
to environmental stimuli, and the sleep homeostat, which
rises as a function of time awake. There is a normal
distribution across the population in how the circadian
system aligns with typical day and night resulting in
varying circadian preferences called chronotypes. A portion
of the variation in the population is controlled by genetics
as shown by the single-gene mutations that confer extreme
early or late chronotypes. Similarly, there is a normal
distribution across the population in sleep duration.
Genetic variations have been identified that lead to a short
sleep phenotype in which individuals sleep only 4-6.5 h
nightly. Negative health consequences have been identified
when individuals do not sleep at their ideal circadian
timing or are sleep deprived relative to intrinsic sleep
need. Whether familial natural short sleepers are at risk of
the health consequences associated with a short sleep
duration based on population data is not known. More work
needs to be done to better assess for an individual's
chronotype and degree of sleep deprivation to answer these
questions.},
Doi = {10.1038/s41386-019-0476-7},
Key = {fds345926}
}
@article{fds345927,
Author = {Krystal, AD},
Title = {Sleep therapeutics and neuropsychiatric illness.},
Journal = {Neuropsychopharmacology},
Volume = {45},
Number = {1},
Pages = {166-175},
Year = {2020},
Month = {January},
url = {http://dx.doi.org/10.1038/s41386-019-0474-9},
Abstract = {Alterations in sleep are extremely common in patients with
neuropsychiatric illness. In addition, sleep disorders such
as insomnia, obstructive sleep apnea, rapid eye movement
sleep behavior disorder, and circadian rhythm disorders
commonly occur at a rate greater than the general population
in neuropsychiatric conditions. Historically, sleep problems
have been viewed as symptoms of associated neuropsychiatric
disorders. However, there is increasing evidence suggesting
a complex inter-relationship with possible bidirectional
causality. The inter-relatedness of these conditions
represents an opportunity for understanding mechanisms and
improving clinical treatment. To the extent that sleep
problems affect neuropsychiatric conditions, it may be
possible to address sleep problems and have a positive
impact on the course of neuropsychiatric illnesses. Further,
some treatments for sleep disorders have direct effects on
neuropsychiatric illnesses that may be unrelated to their
effects on sleep disorders. Similarly, neuropsychiatric
conditions and their treatments can affect sleep and sleep
disorders. This article reviews available evidence on the
effects of therapies for sleep disorders on neuropsychiatric
conditions and also secondarily considers the impacts of
therapies for neuropsychiatric conditions on sleep. Primary
goals of this review are to identify gaps in current
research, to determine the extent to which the
cross-therapeutic effects of these treatments help to
elucidate therapeutic or pathological mechanisms, and to
assist clinicians in optimizing therapeutic choice in
patients with sleep disorders and neuropsychiatric
conditions.},
Doi = {10.1038/s41386-019-0474-9},
Key = {fds345927}
}
@article{fds349368,
Author = {Scangos, KW and Ahmad, HS and Shafi, A and Sellers, KK and Dawes, HE and Krystal, A and Chang, EF},
Title = {Pilot Study of An Intracranial Electroencephalography
Biomarker of Depressive Symptoms in Epilepsy.},
Journal = {J Neuropsychiatry Clin Neurosci},
Volume = {32},
Number = {2},
Pages = {185-190},
Year = {2020},
url = {http://dx.doi.org/10.1176/appi.neuropsych.19030081},
Abstract = {OBJECTIVES: Adult patients with epilepsy have an increased
prevalence of major depressive disorder (MDD). Intracranial
EEG (iEEG) captured during extended inpatient monitoring of
patients with treatment-resistant epilepsy offers a
particularly promising method to study MDD networks in
epilepsy. METHODS: The authors used 24 hours of
resting-state iEEG to examine the neural activity patterns
within corticolimbic structures that reflected the presence
of depressive symptoms in 13 adults with
medication-refractory epilepsy. Principal component analysis
was performed on the z-scored mean relative power in five
standard frequency bands averaged across electrodes within a
region. RESULTS: Principal component 3 was a statistically
significant predictor of the presence of depressive symptoms
(R2=0.35, p=0.014). A balanced logistic classifier model
using principal component 3 alone correctly classified 78%
of patients as belonging to the group with a high burden of
depressive symptoms or a control group with minimal
depressive symptoms (sensitivity, 75%; specificity, 80%;
area under the curve=0.8, leave-one-out cross validation).
Classification was dependent on beta power throughout the
corticolimbic network and low-frequency cingulate power.
CONCLUSIONS: These finding suggest, for the first time, that
neural features across circuits involved in epilepsy may
distinguish patients who have depressive symptoms from those
who do not. Larger studies are required to validate these
findings and to assess their diagnostic utility in
MDD.},
Doi = {10.1176/appi.neuropsych.19030081},
Key = {fds349368}
}
@article{fds346507,
Author = {McCall, WV and Benca, RM and Rosenquist, PB and Youssef, NA and McCloud,
L and Newman, JC and Case, D and Rumble, ME and Szabo, ST and Phillips, M and Krystal, AD},
Title = {Reducing Suicidal Ideation Through Insomnia Treatment
(REST-IT): A Randomized Clinical Trial.},
Journal = {American Journal of Psychiatry},
Volume = {176},
Number = {11},
Pages = {957-965},
Year = {2019},
Month = {November},
url = {http://dx.doi.org/10.1176/appi.ajp.2019.19030267},
Abstract = {OBJECTIVE: The authors sought to determine whether targeted
treatment of insomnia with controlled-release zolpidem
(zolpidem-CR) in suicidal adults with insomnia would provide
a reduction in suicidal ideation superior to placebo.
METHODS: Reducing Suicidal Ideation Through Insomnia
Treatment was an 8-week three-site double-blind
placebo-controlled parallel-group randomized controlled
trial of zolpidem-CR hypnotic therapy compared with placebo,
in conjunction with an open-label selective serotonin
reuptake inhibitor. Participants were medication-free 18- to
65-year-olds with major depressive disorder, insomnia, and
suicidal ideation. Suicidal ideation was the main outcome,
measured first by the Scale for Suicide Ideation and second
by the Columbia-Suicide Severity Rating Scale (C-SSRS).
RESULTS: A total of 103 participants were randomly assigned
to receive zolpidem-CR (N=51) or placebo (N=52) (64 women
and 39 men; mean age=40.5 years). Zolpidem-CR had a robust
anti-insomnia effect, especially in patients with the most
severe insomnia symptoms. No significant treatment effect
was observed on the Scale for Suicide Ideation (least
squares mean estimate=-0.56, SE=0.83, 95% CI=-2.19, 1.08),
but the reduction in scores was significantly positively
related to improvement in insomnia after accounting for the
effect of other depression symptoms. The C-SSRS indicated
that zolpidem-CR had a significant treatment effect (least
squares mean estimate=-0.26, SE=0.12, 95% CI=-0.50, -0.02).
The advantage for zolpidem-CR in reducing suicidal ideation
on the C-SSRS was greater in patients with more severe
insomnia. No deaths or suicide attempts occurred.
CONCLUSIONS: Although the results do not support the routine
prescription of hypnotic medication for mitigating suicidal
ideation in all depressed outpatients with insomnia, they
suggest that coprescription of a hypnotic during initiation
of an antidepressant may be beneficial in suicidal
outpatients, especially in patients with severe
insomnia.},
Doi = {10.1176/appi.ajp.2019.19030267},
Key = {fds346507}
}
@article{fds346452,
Author = {Krystal, AD and Prather, AA and Ashbrook, LH},
Title = {The assessment and management of insomnia: an
update.},
Journal = {World Psychiatry : Official Journal of the World Psychiatric
Association (Wpa)},
Volume = {18},
Number = {3},
Pages = {337-352},
Year = {2019},
Month = {October},
url = {http://dx.doi.org/10.1002/wps.20674},
Abstract = {Insomnia poses significant challenges to public health. It
is a common condition associated with marked impairment in
function and quality of life, psychiatric and physical
morbidity, and accidents. As such, it is important that
effective treatment is provided in clinical practice. To
this end, this paper reviews critical aspects of the
assessment of insomnia and the available treatment options.
These options include both non-medication treatments, most
notably cognitive behavioral therapy for insomnia, and a
variety of pharmacologic therapies such as benzodiazepines,
"z-drugs", melatonin receptor agonists, selective histamine
H1 antagonists, orexin antagonists, antidepressants,
antipsychotics, anticonvulsants, and non-selective
antihistamines. A review of the available research indicates
that rigorous double-blind, randomized, controlled trials
are lacking for some of the most commonly administered
insomnia therapies. However, there are an array of
interventions which have been demonstrated to have
therapeutic effects in insomnia in trials with the above
features, and whose risk/benefit profiles have been well
characterized. These interventions can form the basis for
systematic, evidence-based treatment of insomnia in clinical
practice. We review this evidence base and highlight areas
where more studies are needed, with the aim of providing a
resource for improving the clinical management of the many
patients with insomnia.},
Doi = {10.1002/wps.20674},
Key = {fds346452}
}
@article{fds346453,
Author = {Shi, G and Xing, L and Wu, D and Bhattacharyya, BJ and Jones, CR and McMahon, T and Chong, SYC and Chen, JA and Coppola, G and Geschwind, D and Krystal, A and Ptáček, LJ and Fu, Y-H},
Title = {A Rare Mutation of β1-Adrenergic Receptor Affects
Sleep/Wake Behaviors.},
Journal = {Neuron},
Volume = {103},
Number = {6},
Pages = {1044-1055.e7},
Year = {2019},
Month = {September},
url = {http://dx.doi.org/10.1016/j.neuron.2019.07.026},
Abstract = {Sleep is crucial for our survival, and many diseases are
linked to long-term poor sleep quality. Before we can use
sleep to enhance our health and performance and alleviate
diseases associated with poor sleep, a greater understanding
of sleep regulation is necessary. We have identified a
mutation in the β1-adrenergic receptor gene in humans who
require fewer hours of sleep than most. In vitro, this
mutation leads to decreased protein stability and dampened
signaling in response to agonist treatment. In vivo, the
mice carrying the same mutation demonstrated short sleep
behavior. We found that this receptor is highly expressed in
the dorsal pons and that these ADRB1+ neurons are active
during rapid eye movement (REM) sleep and wakefulness.
Activating these neurons can lead to wakefulness, and the
activity of these neurons is affected by the mutation. These
results highlight the important role of β1-adrenergic
receptors in sleep/wake regulation.},
Doi = {10.1016/j.neuron.2019.07.026},
Key = {fds346453}
}
@article{fds343782,
Author = {Krystal, AD and Prather, AA},
Title = {Sleep Pharmacogenetics: The Promise of Precision
Medicine.},
Journal = {Sleep Med Clin},
Volume = {14},
Number = {3},
Pages = {317-331},
Year = {2019},
Month = {September},
url = {http://dx.doi.org/10.1016/j.jsmc.2019.05.003},
Abstract = {Pharmacogenetics is the branch of personalized medicine
concerned with the variability in drug response occurring
because of heredity. Advances in genetics research, and
decreasing costs of gene sequencing, are promoting
tremendous growth in pharmacogenetics in all areas of
medicine, including sleep medicine. This article reviews the
body of research indicating that there are genetic
variations that affect the therapeutic actions and adverse
effects of agents used for the treatment of sleep disorders
to show the potential of pharmacogenetics to improve the
clinical practice of sleep medicine.},
Doi = {10.1016/j.jsmc.2019.05.003},
Key = {fds343782}
}
@article{fds344648,
Author = {McCall, WV and Benca, RM and Rumble, ME and Case, D and Rosenquist, PB and Krystal, AD},
Title = {Prevalence of obstructive sleep apnea in suicidal patients
with major depressive disorder.},
Journal = {J Psychiatr Res},
Volume = {116},
Pages = {147-150},
Year = {2019},
Month = {September},
url = {http://dx.doi.org/10.1016/j.jpsychires.2019.06.015},
Abstract = {In this paper, we report the rate of previously undiagnosed
obstructive sleep apnea (OSA) in a randomized clinical trial
(RCT) of suicidal patients with major depressive disorder
(MDD). One hundred and twenty-five suicidal adults with MDD
were recruited into a RCT. None were suspected to have OSA.
Fourteen percent met diagnostic criteria for OSA. The Apnea
Hypopnea Index (AHI) was predicted by increasing age, male
sex, and higher Body Mass Index. However, neither the degree
of daytime sleepiness nor the degree of insomnia predicted
AHI severity. A high degree of suspicion is warranted for
OSA in suicidal patients with MDD, and for patients with
treatment-resistant depression. ClinicalTrials.gov
identifier: NCT01689909.},
Doi = {10.1016/j.jpsychires.2019.06.015},
Key = {fds344648}
}
@article{fds344899,
Author = {Wilson, S and Anderson, K and Baldwin, D and Dijk, D-J and Espie, A and Espie, C and Gringras, P and Krystal, A and Nutt, D and Selsick, H and Sharpley, A},
Title = {British Association for Psychopharmacology consensus
statement on evidence-based treatment of insomnia,
parasomnias and circadian rhythm disorders: An
update.},
Journal = {J Psychopharmacol},
Volume = {33},
Number = {8},
Pages = {923-947},
Year = {2019},
Month = {August},
url = {http://dx.doi.org/10.1177/0269881119855343},
Abstract = {This British Association for Psychopharmacology guideline
replaces the original version published in 2010, and
contains updated information and recommendations. A
consensus meeting was held in London in October 2017
attended by recognised experts and advocates in the field.
They were asked to provide a review of the literature and
identification of the standard of evidence in their area,
with an emphasis on meta-analyses, systematic reviews and
randomised controlled trials where available, plus updates
on current clinical practice. Each presentation was followed
by discussion, aiming to reach consensus where the evidence
and/or clinical experience was considered adequate, or
otherwise to flag the area as a direction for future
research. A draft of the proceedings was circulated to all
speakers for comments, which were incorporated into the
final statement.},
Doi = {10.1177/0269881119855343},
Key = {fds344899}
}
@article{fds343631,
Author = {Scangos, KW and Weiner, RD and Coffey, EC and Krystal,
AD},
Title = {An Electrophysiological Biomarker That May Predict Treatment
Response to ECT.},
Journal = {J Ect},
Volume = {35},
Number = {2},
Pages = {95-102},
Year = {2019},
Month = {June},
url = {http://dx.doi.org/10.1097/YCT.0000000000000557},
Abstract = {OBJECTIVE: Electroconvulsive therapy (ECT) is the most
effective treatment for major depression but also carries
risk of cognitive side effects. The ability to predict
whether treatment will be effective before initiation of
treatment could significantly improve quality of care,
reduce suffering, and diminish costs. We sought to carry out
a comprehensive and definitive study of the relationship
between the background electroencephalography (EEG) and
therapeutic response to ECT. METHODS: Twenty-one channel
resting EEG was collected pre-ECT and 2 to 3 days after ECT
course from 2 separate data sets, one to develop an EEG
model of therapeutic response (n = 30) and a second to test
this model (n = 40). A 3-way principal components analysis
was applied and coherence and spectral amplitude across 6
frequency bands were examined. The primary outcome measure
was the Montgomery-Asberg Rating Scale (MADRS). RESULTS:
Four patterns of amplitude and coherence along with baseline
MADRS score accounted for 85% of the variance in
posttreatment course MADRS score in study 1 (R = 0.85, F =
11.7, P < 0.0002) and 53% of the variance in MADRS score in
study 2 (R = 0.53, F = 5.5, P < 0.003). Greater pre-ECT
course anterior delta coherence accounted for the majority
of variance in therapeutic response (study 1: R = 0.44, P =
0.01; study 2: R = 0.16, P = 0.008). CONCLUSIONS: These
results suggest a putative electrophysiological biomarker
that can predict therapeutic response before a course of
ECT. Greater baseline anterior delta coherence is
significantly associated with a better subsequent
therapeutic response and could be indicative of intact
circuitry allowing for improved seizure propagation.},
Doi = {10.1097/YCT.0000000000000557},
Key = {fds343631}
}
@article{fds342842,
Author = {Asarnow, LD and Bei, B and Krystal, A and Buysse, DJ and Thase, ME and Edinger, JD and Manber, R},
Title = {Circadian Preference as a Moderator of Depression Outcome
Following Cognitive Behavioral Therapy for Insomnia Plus
Antidepressant Medications: A Report From the TRIAD
Study.},
Journal = {J Clin Sleep Med},
Volume = {15},
Number = {4},
Pages = {573-580},
Year = {2019},
Month = {April},
url = {http://dx.doi.org/10.5664/jcsm.7716},
Abstract = {STUDY OBJECTIVES: We previously presented results from a
randomized controlled trial that examined the effects of
antidepressant medication plus cognitive behavioral therapy
for insomnia (CBT-I) among patients with major depressive
disorder (MDD) and insomnia. The current secondary analysis
aims to examine whether circadian preference moderated the
reduction in depression and insomnia symptom severity during
this trial. METHODS: A total of 139 adult participants with
MDD and insomnia disorder were treated with antidepressant
medication and randomized to receive 7 sessions of CBT-I or
a control therapy (CTRL). Circadian preference (eveningness)
was measured using the Composite Scale of Morningness (CSM).
Depression symptom severity was assessed using the Hamilton
Depression Rating Scale (HDRS); insomnia symptom severity
was assessed using the Insomnia Severity Inventory (ISI).
The moderating role of circadian preference on changes in
HRSD and ISI was assessed via latent growth models within
the framework of structural equation modeling. RESULTS:
Greater evening preference was associated with smaller
reduction in HDRS (P = .03) from baseline to week 6 across
treatment groups. The interaction between CSM and treatment
group was also significant (P = .02), indicating that
participants with greater evening preference in the CTRL
group had significantly smaller HDRS reduction than those
with greater evening preference in the CBT-I group.
Circadian preference did not share significant associations
with ISI (all P > .30). CONCLUSIONS: Individuals with MDD
and insomnia who have an evening preference are at increased
risk for poor response to pharmacological depression
treatment augmented with either CBT-I or CTRL behavioral
insomnia treatment. However, evening types have better
depression outcomes when treated with CBT-I than with CTRL
for insomnia.},
Doi = {10.5664/jcsm.7716},
Key = {fds342842}
}
@article{fds339682,
Author = {Herring, WJ and Roth, T and Krystal, AD and Michelson,
D},
Title = {Orexin receptor antagonists for the treatment of insomnia
and potential treatment of other neuropsychiatric
indications.},
Journal = {J Sleep Res},
Volume = {28},
Number = {2},
Pages = {e12782},
Year = {2019},
Month = {April},
url = {http://dx.doi.org/10.1111/jsr.12782},
Abstract = {In this review, we outline the role of orexin receptor
antagonists in disorders of sleep/wake and other potential
neuropsychiatric conditions, with a focus on suvorexant,
which is currently the only approved agent in this class.
The efficacy of suvorexant was established in Phase 2-3
trials with treatment durations ranging from 1 to
12 months in patients with insomnia. Suvorexant is
effective at improving sleep assessed by patient self-report
and by polysomnography, with generally little effect on
underlying sleep architecture. The main side-effect is next
day somnolence. With the growing realization of the
important connections between sleep and other disorders,
studies are ongoing to explore this novel mechanism in other
disorders such as Alzheimer's disease and
depression.},
Doi = {10.1111/jsr.12782},
Key = {fds339682}
}
@article{fds341019,
Author = {Strollo, PJ and Hedner, J and Collop, N and Lorch, DG and Chen, D and Carter, LP and Lu, Y and Lee, L and Black, J and Pépin, J-L and Redline,
S and Tones 4 Study Investigators},
Title = {Solriamfetol for the Treatment of Excessive Sleepiness in
OSA: A Placebo-Controlled Randomized Withdrawal
Study.},
Journal = {Chest},
Volume = {155},
Number = {2},
Pages = {364-374},
Year = {2019},
Month = {February},
url = {http://dx.doi.org/10.1016/j.chest.2018.11.005},
Abstract = {BACKGROUND: Excessive sleepiness (ES) is a common symptom of
OSA, which often persists despite primary OSA therapy. This
phase III randomized withdrawal trial evaluated solriamfetol
(JZP-110) for the treatment of ES in adults with OSA.
METHODS: After 2 weeks of clinical titration (n = 174) and
2 weeks of stable dose administration (n = 148),
participants who reported improvement on the Patient Global
Impression of Change (PGI-C) and had numerical improvements
on the Maintenance of Wakefulness Test (MWT) and Epworth
Sleepiness Scale (ESS) were randomly assigned to placebo
(n = 62) or solriamfetol (n = 62) for 2 additional weeks.
Coprimary end points were change from weeks 4 to 6 in MWT
and ESS. RESULTS: In the modified intention-to-treat
population (n = 122), MWT mean sleep latencies and ESS
scores improved from baseline to week 4 (from 12.3-13.1 to
29.0-31.7 minutes and from 15.3-16.0 to 5.9-6.4,
respectively). From weeks 4 to 6, participants treated with
solriamfetol maintained improvements (least squares [LS]
mean [SE] changes of -1.0 [1.4] minutes on MWT and -0.1
[0.7] on ESS), whereas participants treated with placebo
worsened (LS mean [SE] change of -12.1 [1.3] minutes on MWT
and 4.5 [0.7] on ESS); LS mean differences between
treatments were 11.2 minutes (95% CI, 7.8-14.6) and -4.6
(95% CI, -6.4 to -2.8) on MWT and ESS, respectively.
Fewer participants treated with solriamfetol reported
worsening on the PGI-C from weeks 4 to 6 (20% vs 50%; P =
.0005). Common adverse events included headache, dry mouth,
nausea, dizziness, and insomnia. CONCLUSIONS: This study
demonstrated maintenance of solriamfetol efficacy and safety
over 6 weeks. TRIAL REGISTRY: ClinicalTrials.gov; No.:
NCT02348619; URL: www.clinicaltrials.gov; EudraCT No.:
2014-005515-16.},
Doi = {10.1016/j.chest.2018.11.005},
Key = {fds341019}
}
@article{fds340177,
Author = {Ohayon, MM and Black, J and Krystal, AD and Shapiro, CM and Swick, TJ and Bogan, R and Wells, CC},
Title = {Longitudinal study of narcolepsy symptoms in first, second,
and third-degree relatives of simplex and multiplex
narcolepsy families.},
Journal = {Sleep Med},
Volume = {53},
Pages = {88-93},
Year = {2019},
Month = {January},
url = {http://dx.doi.org/10.1016/j.sleep.2018.06.015},
Abstract = {OBJECTIVE: To assess the evolution of narcolepsy symptoms in
first-, second, and third-degree relatives and to compare
multiplex and simplex families. METHODS: A total of 4045
family members and 362 narcoleptic individuals were entered
in the study; with 3255 family members interviewed twice,
five to seven years apart. A control group (n = 178)
composed of spouses or housemates was also interviewed
twice. Family members were divided according to their blood
relationship with the probands and further divided into
multiplex (ie, more than one narcolepsy cases) and simplex
(only one narcolepsy case) families. Telephone interviews
were conducted with the help of the Sleep-EVAL system;
narcolepsy probands were evaluated and diagnosed by a Sleep
Specialist in a Sleep Clinic Center. RESULTS: A total of
1123 family members from 72 families were identified as
members of multiplex families while the rest of the sample
were a part of simplex families (n = 2132). Multiplex
families had higher incidence and chronicity of
hypersomnolence than the simplex family members and the
control group. For cataplexy-like symptoms, only prevalence
at the time of the first assessment distinguished multiplex
(5.5%) and simplex (2.9%) families. Prevalence of sleep
paralysis was higher among the first- and second-degree
relatives coming from multiplex families, while incidence
was the highest among second- and third-degree relatives.
Hypnagogic hallucinations had similar prevalence between
multiplex and simplex families but the incidence and
chronicity were significantly higher among multiplex
families. For each symptom, predictive factors were also
determined in simplex and multiplex families. CONCLUSIONS:
Our results show that individuals coming from multiplex
families are at greater risks of a broad range of narcolepsy
symptoms compared to simplex families.},
Doi = {10.1016/j.sleep.2018.06.015},
Key = {fds340177}
}
@article{fds341573,
Author = {La, AL and Walsh, CM and Neylan, TC and Vossel, KA and Yaffe, K and Krystal, AD and Miller, BL and Karageorgiou, E},
Title = {Long-Term Trazodone Use and Cognition: A Potential
Therapeutic Role for Slow-Wave Sleep Enhancers.},
Journal = {J Alzheimers Dis},
Volume = {67},
Number = {3},
Pages = {911-921},
Year = {2019},
url = {http://dx.doi.org/10.3233/JAD-181145},
Abstract = {BACKGROUND: Recent studies reveal an association between
slow-wave sleep (SWS), amyloid-β aggregation, and
cognition. OBJECTIVE: This retrospective study examines
whether long-term use of trazodone, an SWS enhancer, is
associated with delayed cognitive decline. METHODS: We
identified 25 regular trazodone users (mean age 75.4±7.5; 9
women, 16 men) who carried a diagnosis of Alzheimer's
dementia, mild cognitive impairment, or normal cognition,
and 25 propensity-matched trazodone non-users (mean age
74.5±8.0; 13 women, 12 men), accounting for age, sex,
education, type of sleep deficit (hypersomnia, insomnia,
parasomnia), diagnosis, and baseline Mini-Mental State
Examination (MMSE). Longitudinal group differences in
cognitive testing were evaluated through repeated measures
tests over an average inter-evaluation interval of four
years. RESULTS: Trazodone non-users had 2.6-fold faster
decline MMSE (primary outcome) compared to trazodone users,
0.27 (95% confidence interval [CI]: 0.07-0.48) versus 0.70
(95% CI: 0.50-0.90) points per year (p = 0.023). The
observed effects were especially associated with subjective
improvement of sleep complaints in post-hoc analyses
(p = 0.0006). Secondary outcomes of other cognitive and
functional scores had variable worsening in non-users and
varied in significance when accounting for co-administered
medications and multiple comparisons. Trazodone effects on
MMSE remained significant within participants with
AD-predicted pathology, with 2.4-fold faster decline in
non-users (p = 0.038). CONCLUSIONS: These results
suggest an association between trazodone use and delayed
cognitive decline, adding support for a potentially
attractive and cost-effective intervention in dementia.
Whether the observed relationship of trazodone to cognitive
function is causal or an indirect marker of other effects,
such as treated sleep disruption, and if such effects are
mediated through SWS enhancement requires confirmation
through prospective studies.},
Doi = {10.3233/JAD-181145},
Key = {fds341573}
}
@article{fds340795,
Author = {Krystal, AD and Pizzagalli, DA and Mathew, SJ and Sanacora, G and Keefe,
R and Song, A and Calabrese, J and Goddard, A and Goodman, W and Lisanby,
SH and Smoski, M and Weiner, R and Iosifescu, D and Nurnberger, J and Szabo, S and Murrough, J and Shekhar, A and Potter,
W},
Title = {The first implementation of the NIMH FAST-FAIL approach to
psychiatric drug development.},
Journal = {Nat Rev Drug Discov},
Volume = {18},
Number = {1},
Pages = {82-84},
Year = {2018},
Month = {December},
url = {http://dx.doi.org/10.1038/nrd.2018.222},
Doi = {10.1038/nrd.2018.222},
Key = {fds340795}
}
@article{fds336979,
Author = {Dominguez, JE and Habib, AS and Krystal, AD},
Title = {A review of the associations between obstructive sleep apnea
and hypertensive disorders of pregnancy and possible
mechanisms of disease.},
Journal = {Sleep Med Rev},
Volume = {42},
Pages = {37-46},
Year = {2018},
Month = {December},
url = {http://dx.doi.org/10.1016/j.smrv.2018.05.004},
Abstract = {Obesity is prevalent among pregnant women in the United
States; 15-20% of obese pregnant women have obstructive
sleep apnea. The prevalence of obstructive sleep apnea
increases along with body mass index, age and in the
presence of other co-morbidities. Untreated obstructive
sleep apnea in women is associated with a range of
cardiovascular, pulmonary and metabolic co-morbidities;
recent studies suggest that women with obstructive sleep
apnea in pregnancy may be at significantly greater risk of
entering pregnancy with chronic hypertension and/or of
developing hypertensive disorders of pregnancy: gestational
hypertension; preeclampsia; or eclampsia. This has serious
public health implications; hypertensive disorders of
pregnancy are a major cause of maternal and neonatal
morbidity and mortality and are associated with a greater
lifetime risk for cardiovascular disease. The mechanisms
that associated obstructive sleep apnea with hypertensive
disorders of pregnancy have not been defined, but several
pathways are scientifically plausible. In this review, we
will present a comprehensive literature review of the
following: the associations between obstructive sleep apnea
and hypertensive disorders of pregnancy; the proposed
mechanisms that may connect obstructive sleep apnea and
hypertensive disorders of pregnancy; and the effectiveness
of treatment at mitigating these adverse
outcomes.},
Doi = {10.1016/j.smrv.2018.05.004},
Key = {fds336979}
}
@article{fds339612,
Author = {Dominguez, JE and Grotegut, CA and Cooter, M and Krystal, AD and Habib,
AS},
Title = {Screening extremely obese pregnant women for obstructive
sleep apnea.},
Journal = {American Journal of Obstetrics and Gynecology},
Volume = {219},
Number = {6},
Pages = {613.e1-613.e10},
Year = {2018},
Month = {December},
url = {http://dx.doi.org/10.1016/j.ajog.2018.09.001},
Abstract = {BACKGROUND: Obesity is prevalent among pregnant women in the
United States; obstructive sleep apnea is highly comorbid
with obesity and is associated with adverse pregnancy
outcomes. Screening for obstructive sleep apnea in pregnant
women has remained a challenge because of a lack of
validated screening tools. OBJECTIVE: The purpose of this
study was to evaluate established obstructive sleep apnea
screening tools, a sleepiness scale, and individual
component items in a cohort of pregnant women with extreme
obesity in mid pregnancy with the use of objective testing
to determine obstructive sleep apnea status and to describe
the prevalence of obstructive sleep apnea among women with
extreme obesity. STUDY DESIGN: Adult pregnant subjects,
between 24 and 35 weeks gestation, with a body mass index
≥40 kg/m2 at the time of enrollment completed obstructive
sleep apnea screening tools (Berlin Questionnaire, American
Society of Anesthesiologists checklist, and STOP-BANG
questionnaire) and the Epworth Sleepiness Scale; they also
underwent physical examination of the neck, mouth, and
airway. The published obstructive sleep apnea in pregnancy
prediction score was calculated for each subject.
Obstructive sleep apnea status for each subject was
determined by the results of an overnight, unattended type
III home sleep apnea test. RESULTS: Twenty-four percent of
pregnant women with extreme obesity had obstructive sleep
apnea on home sleep apnea testing in mid pregnancy
(Apnea-Hypopnea Index, ≥5 events per hour]. Established
obstructive sleep apnea screening tools performed very
poorly to screen for obstructive sleep apnea in this cohort.
Age, body mass index, neck circumference, frequently
witnessed apneas, and highly likely to fall asleep while
driving were associated most strongly with obstructive sleep
apnea status in this cohort. CONCLUSION: We found that 24%
of pregnant women with body mass index ≥40 kg/m2 between
24 and 35 weeks gestation have obstructive sleep apnea,
defined as Apnea-Hypopnea Index ≥5 events per hour on an
overnight type III home sleep apnea test. We found the
Berlin Questionnaire, American Society of Anesthesiologists
checklist, STOP-BANG, obstructive sleep apnea in pregnancy
score by Facco et al, and the Epworth Sleepiness Scale were
not useful screening tools for obstructive sleep apnea in a
cohort of obese pregnant women. However, age, body mass
index, neck circumference, frequently witnessed apneas, and
likely to fall asleep while driving were associated with
obstructive sleep apnea in this cohort. Further studies are
needed to adjust the criteria and thresholds within the
available screening tools to better predict obstructive
sleep apnea in pregnant women with obesity.},
Doi = {10.1016/j.ajog.2018.09.001},
Key = {fds339612}
}
@article{fds339929,
Author = {Szabo, ST and Kandra, K and Krystal, AD},
Title = {Effect of γ-hydroxybutyrate (Xyrem) on locus coeruleus
activity as measured by pupillometry in a patient with
narcolepsy.},
Journal = {International Journal of Clinical Pharmacology and
Therapeutics},
Volume = {56},
Number = {12},
Pages = {620-622},
Year = {2018},
Month = {December},
url = {http://dx.doi.org/10.5414/CP202661},
Doi = {10.5414/CP202661},
Key = {fds339929}
}
@article{fds339375,
Author = {Dominguez, JE and Krystal, AD and Habib, AS},
Title = {Obstructive Sleep Apnea in Pregnant Women: A Review of
Pregnancy Outcomes and an Approach to Management.},
Journal = {Anesth Analg},
Volume = {127},
Number = {5},
Pages = {1167-1177},
Year = {2018},
Month = {November},
url = {http://dx.doi.org/10.1213/ANE.0000000000003335},
Abstract = {Among obese pregnant women, 15%-20% have obstructive sleep
apnea (OSA) and this prevalence increases along with body
mass index and in the presence of other comorbidities.
Prepregnancy obesity and pregnancy-related weight gain are
certainly risk factors for sleep-disordered breathing in
pregnancy, but certain physiologic changes of pregnancy may
also increase a woman's risk of developing or worsening OSA.
While it has been shown that untreated OSA in postmenopausal
women is associated with a range of cardiovascular,
pulmonary, and metabolic comorbidities, a body of literature
is emerging that suggests OSA may also have serious
implications for the health of mothers and fetuses during
and after pregnancy. In this review, we discuss the
following: pregnancy as a vulnerable period for the
development or worsening of OSA; the associations between
OSA and maternal and fetal outcomes; the current screening
modalities for OSA in pregnancy; and current recommendations
regarding peripartum management of OSA.},
Doi = {10.1213/ANE.0000000000003335},
Key = {fds339375}
}
@article{fds333559,
Author = {Lundeen, J and McCall, WV and Krystal, A and Looney,
S},
Title = {Validating functional data analysis measures from 24-h
actigraphy data},
Journal = {Biological Rhythm Research},
Volume = {49},
Number = {5},
Pages = {797-810},
Publisher = {Informa UK Limited},
Year = {2018},
Month = {September},
url = {http://dx.doi.org/10.1080/09291016.2018.1424771},
Abstract = {The timing of sleep and wakefulness are under the influence
of the circadian pacemaker in the suprachiasmatic nucleus,
and the set-point for the circadian pacemaker is revealed by
the time of onset of the secretion of melatonin under dim
light conditions (DLMO). Measuring DLMO is time intensive
and requires biochemical assays; hence it would be desirable
to develop simpler alternatives to DLMO measurement that
would otherwise provide similar information about health and
illness. Continuous, multi-day measurement of actigraphy can
be processed to reveal underlying features such as the time
of greatest activity (acrophase), or the time of least
activity (bathyphase). In this paper, we explore the
calculation of the acrophase and bathyphase using a
statistical approach called functional data analysis (FDA),
and validated the FDA-calculated bathyphase by correlating
it with morningness–eveningness self-reports from 47
depressed adults.},
Doi = {10.1080/09291016.2018.1424771},
Key = {fds333559}
}
@article{fds339868,
Author = {Beppler, EC and Dieffenderfer, J and Songkakul, T and Krystal, A and Bozkurt, A},
Title = {An Ultra-miniaturized Near Infrared Spectroscopy System to
Assess Sleep Apnea in Children with Down
Syndrome.},
Journal = {Annu Int Conf Ieee Eng Med Biol Soc},
Volume = {2018},
Pages = {2877-2880},
Year = {2018},
Month = {July},
url = {http://dx.doi.org/10.1109/EMBC.2018.8513038},
Abstract = {Down syndrome is one of the health disorders that interferes
with regular and healthy sleep. Most children with Down
syndrome are referred to a sleep clinic for the assessment
of the severity of their apnea. Regular polysomnography
based assessment of apnea has been challenging with this
sensitive patient population. We present our efforts towards
developing a flexible adhesive bandage sized near infrared
spectroscopy system (pediBand) for home-assessment of apnea
in children with Down syndrome. Combined with inertial
measurement units, pediBand record heart rate, heart rate
variability, respiratory rate, arterial oxygen saturation
and cerebral oxygen saturation. These are the essential
parameters to assess sleep apnea and could also potentially
be used in the assessment of sleep performance in general. A
modified version of pediBand system was evaluated on adult
patients and successfully demonstrated the changes in
hemodynamic system triggered by sleep apnea.},
Doi = {10.1109/EMBC.2018.8513038},
Key = {fds339868}
}
@article{fds333033,
Author = {Bei, B and Asarnow, LD and Krystal, A and Edinger, JD and Buysse, DJ and Manber, R},
Title = {Treating insomnia in depression: Insomnia related factors
predict long-term depression trajectories.},
Journal = {J Consult Clin Psychol},
Volume = {86},
Number = {3},
Pages = {282-293},
Publisher = {American Psychological Association (APA)},
Year = {2018},
Month = {March},
url = {http://dx.doi.org/10.1037/ccp0000282},
Abstract = {OBJECTIVE: Insomnia and major depressive disorders (MDD)
often co-occur, and such comorbidity has been associated
with poorer outcomes for both conditions. However,
individual differences in depressive symptom trajectories
during and after treatment are poorly understood in comorbid
insomnia and depression. This study explored the
heterogeneity in long-term depression change trajectories,
and examined their correlates, particularly insomnia-related
characteristics. METHOD: Participants were 148 adults (age M
± SD = 46.6 ± 12.6, 73.0% female) with insomnia and MDD
who received antidepressant pharmacotherapy, and were
randomized to 7-session Cognitive Behavioral Therapy for
Insomnia or control conditions over 16 weeks with 2-year
follow-ups. Depression and insomnia severity were assessed
at baseline, biweekly during treatment, and every 4 months
thereafter. Sleep effort and beliefs about sleep were also
assessed. RESULTS: Growth mixture modeling revealed three
trajectories: (a) Partial-Responders (68.9%) had moderate
symptom reduction during early treatment (p value < .001)
and maintained mild depression during follow-ups. (b)
Initial-Responders (17.6%) had marked symptom reduction
during treatment (p values < .001) and low depression
severity at posttreatment, but increased severity over
follow-up (p value < .001). (c) Optimal-Responders (13.5%)
achieved most gains during early treatment (p value < .001),
continued to improve (p value < .01) and maintained minimal
depression during follow-ups. The classes did not differ
significantly on baseline measures or treatment received,
but differed on insomnia-related measures after treatment
began (p values < .05): Optimal-Responders consistently
endorsed the lowest insomnia severity, sleep effort, and
unhelpful beliefs about sleep. CONCLUSIONS: Three depression
symptom trajectories were observed among patients with
comorbid insomnia and MDD. These trajectories were
associated with insomnia-related constructs after commencing
treatment. Early changes in insomnia characteristics may
predict long-term depression outcomes. (PsycINFO Database
Record},
Doi = {10.1037/ccp0000282},
Key = {fds333033}
}
@article{fds331189,
Author = {Rumble, ME and Dickson, D and McCall, WV and Krystal, AD and Case, D and Rosenquist, PB and Benca, RM},
Title = {The relationship of person-specific eveningness chronotype,
greater seasonality, and less rhythmicity to suicidal
behavior: A literature review.},
Journal = {J Affect Disord},
Volume = {227},
Pages = {721-730},
Year = {2018},
Month = {February},
url = {http://dx.doi.org/10.1016/j.jad.2017.11.078},
Abstract = {BACKGROUND: Epidemiological data have demonstrated seasonal
and circadian patterns of suicidal deaths. Several reviews
and meta-analyses have confirmed the relationship between
sleep disturbance and suicidality. However, these
reviews/meta-analyses have not focused on seasonal and
circadian dysfunction in relation to suicidality, despite
the common presence of this dysfunction in patients with
mood disorders. Thus, the current literature review analyzed
studies investigating person-specific chronotype,
seasonality, and rhythmicity in relation to suicidal
thoughts and behaviors. METHODS: Study authors reviewed
articles related to individual-level chronotype,
seasonality, and rhythmicity and suicidality that were
written in English and not case reports or reviews. RESULTS:
This review supports a relationship between an eveningness
chronotype, greater seasonality, and decreased rhythmicity
with suicidal thoughts and behaviors in those with unipolar
depression, as well as in other psychiatric disorders and in
children/adolescents. LIMITATIONS: These findings need to be
explored more fully in mood disordered populations and other
psychiatric populations, in both adults and children, with
objective measurement such as actigraphy, and with
chronotype, seasonality, and rhythmicity as well as broader
sleep disturbance measurement all included so the
construct(s) most strongly linked to suicidality can be best
identified. CONCLUSIONS: Eveningness, greater seasonality,
and less rhythmicity should be considered in individuals who
may be at risk for suicidal thoughts and behaviors and may
be helpful in further tailoring assessment and treatment to
improve patient outcome.},
Doi = {10.1016/j.jad.2017.11.078},
Key = {fds331189}
}
@article{fds331190,
Author = {Valero-Sarmiento, JM and Reynolds, J and Krystal, A and Bozkurt,
A},
Title = {In vitro evaluation of an injectable EEG/ECG sensor for
wireless monitoring of hibernation in endangered animal
species},
Journal = {Ieee Sensors Journal},
Volume = {18},
Number = {2},
Pages = {798-808},
Publisher = {Institute of Electrical and Electronics Engineers
(IEEE)},
Year = {2018},
Month = {January},
url = {http://dx.doi.org/10.1109/JSEN.2017.2772844},
Abstract = {Hibernation is a unique metabolic adaptation employed by
several animal species for survival where its study would
further enhance our understanding of metabolic disorders,
such as diabetes and obesity. As a primate animal with close
genetic ties to humans, the recent discovery of hibernation
in dwarf lemurs of Madagascar has attracted the attention of
researchers. Traditional recording systems require the
physical tethering of the animals to the recording apparatus
or the use of implantable devices. Scalp and needle
electrodes interfere with the natural hibernation process
and limit the continuity of the experiments, while invasive
procedures are banned on endangered species. By integrating
a full-wave rectifier, low-noise signal conditioning
circuit, frequency modulation transmitter, and antenna in a
single application specific integrated circuit (ASIC), we
have developed an ultra-miniaturized wireless system that
measures 34 × 4 × 2.6 mm3 in volume. It only requires
three off-chip components (a coil wound around a ferrite rod
and two external capacitors) to be powered wirelessly
through a 1-MHz inductive link, such that it can be packaged
inside a glass or polymer capsule and injected
subcutaneously underneath the scalp or chest without
requiring a surgery, thereby addressing the shortcomings of
the traditional monitoring systems. Our recording device
provides an input/output correlation coefficient greater
than 80% for input amplitudes ranging from 60 to 260 μVpp,
with a wireless data transmission range of ∼2.5 cm while
operating near the 902-928 MHz ISM frequency band. This
system would enable future studies of electroencephalography
and electrocardiography in hibernating dwarf lemurs. The
ASIC was fabricated using the ON Semiconductor 0.5-μm CMOS
process with an active area of 2.5 × 1 mm2 and has a power
consumption of 7.75 mW from a 3.1 V supply. In this paper,
we demonstrate the in vitro functionality of the system
using simulated physiological signals directly applied to
the ASIC or through standard stainless steel electrodes
immersed in saline solution.},
Doi = {10.1109/JSEN.2017.2772844},
Key = {fds331190}
}
@article{fds331188,
Author = {Loo, CK and Husain, MM and McDonald, WM and Aaronson, S and O'Reardon,
JP and Alonzo, A and Weickert, CS and Martin, DM and McClintock, SM and Mohan, A and Lisanby, SH and International Consortium of Research
in tDCS (ICRT)},
Title = {International randomized-controlled trial of transcranial
Direct Current Stimulation in depression.},
Journal = {Brain Stimul},
Volume = {11},
Number = {1},
Pages = {125-133},
Year = {2018},
url = {http://dx.doi.org/10.1016/j.brs.2017.10.011},
Abstract = {BACKGROUND: Evidence suggests that transcranial Direct
Current Stimulation (tDCS) has antidepressant effects in
unipolar depression, but there is limited information for
patients with bipolar depression. Additionally, prior
research suggests that brain derived neurotrophic factor
(BDNF) Val66Met genotype may moderate response to tDCS.
OBJECTIVE: To examine tDCS efficacy in unipolar and bipolar
depression and assess if BDNF genotype is associated with
antidepressant response to tDCS. METHODS: 130 participants
diagnosed with a major depressive episode were randomized to
receive active (2.5 milliamps (mA), 30 min) or sham
(0.034 mA and two 60-second current ramps up to 1 and
0.5 mA) tDCS to the left prefrontal cortex, administered in
20 sessions over 4 weeks, in a double-blinded, international
multisite study. Mixed effects repeated measures analyses
assessed change in mood and neuropsychological scores in
participants with at least one post-baseline rating in the
unipolar (N = 84) and bipolar (N = 36) samples. RESULTS:
Mood improved significantly over the 4-week treatment period
in both unipolar (p = 0.001) and bipolar groups
(p < 0.001). Among participants with unipolar depression,
there were more remitters in the sham treatment group
(p = 0.03). There was no difference between active and
sham stimulation in the bipolar sample. BDNF genotype was
unrelated to antidepressant outcome. CONCLUSIONS: Overall,
this study found no antidepressant difference between active
and sham stimulation for unipolar or bipolar depression.
However, the possibility that the low current delivered in
the sham tDCS condition was biologically active cannot be
discounted. Moreover, BDNF genotype did not moderate
antidepressant outcome. CLINICAL TRIALS REGISTRATION:
www.clinicaltrials.gov, NCT01562184.},
Doi = {10.1016/j.brs.2017.10.011},
Key = {fds331188}
}
@article{fds336980,
Author = {McClintock, SM and Reti, IM and Carpenter, LL and McDonald, WM and Dubin, M and Taylor, SF and Cook, IA and O'Reardon, J and Husain, MM and Wall, C and Krystal, A and Sampson, S and Morales, O and Nelson, BG and George, MS and Lisanby, SH},
Title = {Dr McClintock and Colleagues Reply.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {79},
Number = {1},
Year = {2018},
url = {http://dx.doi.org/10.4088/JCP.17lr11851a},
Doi = {10.4088/JCP.17lr11851a},
Key = {fds336980}
}
@article{fds327314,
Author = {McClintock, SM and Reti, IM and Carpenter, LL and McDonald, WM and Dubin, M and Taylor, SF and Cook, IA and O'Reardon, J and Husain, MM and Wall, C and Krystal, AD and Sampson, SM and Morales, O and Nelson, BG and Latoussakis, V and George, MS and Lisanby, SH and National Network of
Depression Centers rTMS Task Group, and American Psychiatric
Association Council on Research Task Force on Novel
Biomarkers and Treatments},
Title = {Consensus Recommendations for the Clinical Application of
Repetitive Transcranial Magnetic Stimulation (rTMS) in the
Treatment of Depression.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {79},
Number = {1},
Year = {2018},
url = {http://dx.doi.org/10.4088/JCP.16cs10905},
Abstract = {OBJECTIVE: To provide expert recommendations for the safe
and effective application of repetitive transcranial
magnetic stimulation (rTMS) in the treatment of major
depressive disorder (MDD). PARTICIPANTS: Participants
included a group of 17 expert clinicians and researchers
with expertise in the clinical application of rTMS,
representing both the National Network of Depression Centers
(NNDC) rTMS Task Group and the American Psychiatric
Association Council on Research (APA CoR) Task Force on
Novel Biomarkers and Treatments. EVIDENCE: The consensus
statement is based on a review of extensive literature from
2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990
through 2016. The search terms included variants of major
depressive disorder and transcranial magnetic stimulation.
The results were limited to articles written in English that
focused on adult populations. Of the approximately 1,500
retrieved studies, a total of 118 publications were included
in the consensus statement and were supplemented with expert
opinion to achieve consensus recommendations on key issues
surrounding the administration of rTMS for MDD in clinical
practice settings. CONSENSUS PROCESS: In cases in which the
research evidence was equivocal or unclear, a consensus
decision on how rTMS should be administered was reached by
the authors of this article and is denoted in the article as
"expert opinion." CONCLUSIONS: Multiple randomized
controlled trials and published literature have supported
the safety and efficacy of rTMS antidepressant therapy.
These consensus recommendations, developed by the NNDC rTMS
Task Group and APA CoR Task Force on Novel Biomarkers and
Treatments, provide comprehensive information for the safe
and effective clinical application of rTMS in the treatment
of MDD.},
Doi = {10.4088/JCP.16cs10905},
Key = {fds327314}
}
@article{fds327312,
Author = {Goucher Miranda and H and Krystal, AD and Fierro,
MA},
Title = {Nocturnal Dexmedetomidine in Nonintubated, Critically Ill
Patients: Sleep or Sedation?},
Journal = {Anesthesiology},
Volume = {127},
Number = {2},
Pages = {397-398},
Year = {2017},
Month = {August},
url = {http://dx.doi.org/10.1097/ALN.0000000000001721},
Doi = {10.1097/ALN.0000000000001721},
Key = {fds327312}
}
@article{fds327313,
Author = {Connor, KM and Ceesay, P and Hutzelmann, J and Snavely, D and Krystal,
AD and Trivedi, MH and Thase, M and Lines, C and Herring, WJ and Michelson,
D},
Title = {Phase II Proof-of-Concept Trial of the Orexin Receptor
Antagonist Filorexant (MK-6096) in Patients with Major
Depressive Disorder.},
Journal = {The International Journal of Neuropsychopharmacology},
Volume = {20},
Number = {8},
Pages = {613-618},
Year = {2017},
Month = {August},
url = {http://dx.doi.org/10.1093/ijnp/pyx033},
Abstract = {BACKGROUND: We evaluated the orexin receptor antagonist
filorexant (MK-6096) for treatment augmentation in patients
with major depressive disorder. METHODS: We conducted a
6-week, double-blind, placebo-controlled, parallel-group,
Phase II, proof-of-concept study. Patients with major
depressive disorder (partial responders to ongoing
antidepressant therapy) were randomized 1:1 to once-daily
oral filorexant 10 mg or matching placebo. RESULTS: Due to
enrollment challenges, the study was terminated early,
resulting in insufficient statistical power to detect a
prespecified treatment difference; of 326 patients planned,
129 (40%) were randomized and 128 took treatment. There was
no statistically significant difference in the primary
endpoint of change from baseline to week 6 in Montgomery
Asberg Depression Rating Scale total score; the estimated
treatment difference for filorexant-placebo was -0.7 (with
negative values favoring filorexant) (P=.679). The most
common adverse events were somnolence and suicidal ideation.
CONCLUSIONS: The interpretation of the results is limited by
the enrollment, which was less than originally planned, but
the available data do not suggest efficacy of orexin
receptor antagonism with filorexant for the treatment of
depression. (Clinical Trial Registry: clinicaltrials.gov:
NCT01554176).},
Doi = {10.1093/ijnp/pyx033},
Key = {fds327313}
}
@article{fds326743,
Author = {Evans, JL and Nadler, JW and Preud'homme, XA and Fang, E and Daughtry,
RL and Chapman, JB and Attarian, D and Wellman, S and Krystal,
AD},
Title = {Pilot prospective study of post-surgery sleep and EEG
predictors of post-operative delirium.},
Journal = {Clin Neurophysiol},
Volume = {128},
Number = {8},
Pages = {1421-1425},
Year = {2017},
Month = {August},
url = {http://dx.doi.org/10.1016/j.clinph.2017.05.004},
Abstract = {OBJECTIVE: Delirium is a common post-operative complication
associated with significant costs, morbidity, and mortality.
We sought sleep/EEG predictors of delirium present prior to
delirium symptoms to facilitate developing and targeting
therapies. METHODS: Continuous EEG data were obtained in 12
patients post-orthopedic surgery from the day of surgery
until delirium assessment on post-operative day 2 (POD2).
RESULTS: Diminished total sleep time (r=-0.68; p<0.05) and
longer latency to sleep onset (r=0.67; p<0.05) on the first
night in the hospital were associated with greater POD2
delirium severity. Patients experiencing delirium slept 2.4h
less and took 2h longer to fall asleep. Greater waking EEG
delta power (r=0.84; p<0.05) on POD1 and less non-REM sleep
EEG delta power (r=-0.72; p<0.05) on night 2 also predicted
POD2 delirium severity. CONCLUSIONS: Loss of sleep on night1
post-surgery is an early predictor of subsequent delirium.
EEG Delta Power alterations in waking and sleep appear to be
later indicators of impending delirium. Further work is
needed to evaluate reproducibility/generalizability and
assess whether sleep loss contributes to causing delirium.
SIGNIFICANCE: This first study to prospectively collect
continuous EEG data for an extended period prior to delirium
onset identified EEG-derived indices that predict subsequent
delirium that could aid in developing and targeting
therapies.},
Doi = {10.1016/j.clinph.2017.05.004},
Key = {fds326743}
}
@article{fds324509,
Author = {Samson, DR and Manus, MB and Krystal, AD and Fakir, E and Yu, JJ and Nunn,
CL},
Title = {Segmented sleep in a nonelectric, small-scale agricultural
society in Madagascar.},
Journal = {Am J Hum Biol},
Volume = {29},
Number = {4},
Year = {2017},
Month = {July},
url = {http://dx.doi.org/10.1002/ajhb.22979},
Abstract = {OBJECTIVES: We studied sleep in a rural population in
Madagascar to (i) characterize sleep in an equatorial
small-scale agricultural population without electricity,
(ii) assess whether sleep is linked to noise levels in a
dense population, and (iii) examine the effects of
experimentally introduced artificial light on sleep timing.
METHODS: Using actigraphy, sleep-wake patterns were analyzed
for both daytime napping and nighttime wakefulness in 21
participants for a sum total of 292 days. Functional linear
modeling was used to characterize 24-h time-averaged
circadian patterns and to investigate the effect of
experimentally introduced mobile field lights on sleep
timing. We also obtained the first polysomnography (PSG)
recordings of sleep in a traditional population. RESULTS: In
every measure of sleep duration and quality, the Malagasy
population experienced shorter and lower quality sleep when
compared to similarly measured postindustrial values. The
population slept for a total of 6.5 h per night and napped
during 89% of recorded days. We observed a peak in activity
after midnight for both sexes on 49% of nights, consistent
with segmented sleep. Access to mobile field lights had no
statistical effect on nighttime sleep timing. From PSG, we
documented relatively short rapid eye movement (14%), poor
sleep efficiency (66%), and high wake after sleep onset (162
min). CONCLUSIONS: Sleep in this population is segmented,
similar to the "first" sleep and "second" sleep reported in
the historical record. Moreover, although average sleep
duration and quality were lower than documented in Western
populations, circadian rhythms were more stable across
days.},
Doi = {10.1002/ajhb.22979},
Key = {fds324509}
}
@article{fds326742,
Author = {Herring, WJ and Connor, KM and Snyder, E and Snavely, DB and Zhang, Y and Hutzelmann, J and Matzura-Wolfe, D and Benca, RM and Krystal, AD and Walsh, JK and Lines, C and Roth, T and Michelson,
D},
Title = {Suvorexant in Elderly Patients with Insomnia: Pooled
Analyses of Data from Phase III Randomized Controlled
Clinical Trials.},
Journal = {Am J Geriatr Psychiatry},
Volume = {25},
Number = {7},
Pages = {791-802},
Year = {2017},
Month = {July},
url = {http://dx.doi.org/10.1016/j.jagp.2017.03.004},
Abstract = {OBJECTIVE: Suvorexant is an orexin receptor antagonist
approved for treating insomnia at doses of 10-20 mg.
Previously reported phase III results showed that suvorexant
was effective and well-tolerated in a combined-age
population (elderly and nonelderly adults). The present
analysis evaluated the clinical profile of suvorexant
specifically in the elderly. METHODS: Prespecified subgroup
analyses of pooled 3-month data from two (efficacy) and
three (safety) randomized, double-blind, placebo-controlled,
parallel-group trials. In each trial, elderly (≥65 years)
patients with insomnia were randomized to suvorexant
30 mg, suvorexant 15 mg, and placebo. By design, fewer
patients were randomized to 15 mg. Patient-reported and
polysomnographic (subset of patients) sleep maintenance and
onset endpoints were measured. RESULTS: Suvorexant 30 mg
(N = 319) was effective compared with placebo
(N = 318) on patient-reported and polysomnographic sleep
maintenance, and onset endpoints at Night 1
(polysomnographic endpoints)/Week 1 (patient-reported
endpoints), Month 1, and Month 3. Suvorexant 15 mg
(N = 202 treated) was also effective across these
measures, although the onset effect was less evident at
later time points. The percentages of patients discontinuing
because of adverse events over 3 months were 6.4% for
30 mg (N = 627 treated), 3.5% for 15 mg (N = 202
treated), and 5.5% for placebo (N = 469 treated).
Somnolence was the most common adverse event (8.8% for
30 mg, 5.4% for 15 mg, 3.2% for placebo). CONCLUSION:
Suvorexant generally improved sleep maintenance and onset
over 3 months of nightly treatment and was well-tolerated in
elderly patients with insomnia (clinicaltrials.gov;
NCT01097616, NCT01097629, NCT01021813).},
Doi = {10.1016/j.jagp.2017.03.004},
Key = {fds326742}
}
@article{fds326744,
Author = {Sateia, MJ and Buysse, DJ and Krystal, AD and Neubauer,
DN},
Title = {Adverse Effects of Hypnotic Medications.},
Journal = {J Clin Sleep Med},
Volume = {13},
Number = {6},
Pages = {839},
Year = {2017},
Month = {June},
url = {http://dx.doi.org/10.5664/jcsm.6634},
Doi = {10.5664/jcsm.6634},
Key = {fds326744}
}
@article{fds325519,
Author = {Herring, WJ and Connor, KM and Snyder, E and Snavely, DB and Zhang, Y and Hutzelmann, J and Matzura-Wolfe, D and Benca, RM and Krystal, AD and Walsh, JK and Lines, C and Roth, T and Michelson,
D},
Title = {Clinical profile of suvorexant for the treatment of insomnia
over 3 months in women and men: subgroup analysis of pooled
phase-3 data.},
Journal = {Psychopharmacology (Berl)},
Volume = {234},
Number = {11},
Pages = {1703-1711},
Year = {2017},
Month = {June},
url = {http://dx.doi.org/10.1007/s00213-017-4573-1},
Abstract = {RATIONALE: Sex-related differences in the clinical profiles
of some insomnia medications have been previously reported.
OBJECTIVE: To evaluate the clinical profile of suvorexant, a
novel orexin receptor antagonist approved for treating
insomnia at doses up to 20 mg, by sex subgroups. METHODS:
Efficacy analyses by sex were based on pooled data from two
similar phase 3, randomized, double-blind,
placebo-controlled, 3-month trials in elderly (≥65 years)
and non-elderly (18-64 years) insomnia patients. Two
age-adjusted (non-elderly/elderly) dose regimes of 40/30 and
20/15 mg were evaluated, with fewer patients assigned to
20/15 mg. Efficacy was assessed by patient-reported
outcomes (N = 1264 women, 707 men) and by polysomnography
endpoints in ~75% of patients. Safety analyses by sex
(N = 1744 women, 1065 men) included pooled data from the
two 3-month trials plus 3-month data from a safety trial of
40/30 mg. RESULTS: The sex subgroup efficacy analyses
mirrored the improvements seen for suvorexant 40/30 and
20/15 mg over placebo on patient-reported outcomes and
polysomnography sleep maintenance and onset endpoints in the
primary analyses; 95% CIs excluded zero in favor of
suvorexant for most endpoints in both sexes, and similar
efficacy was observed between sexes (95% CIs overlapped).
Suvorexant was well-tolerated in women and men, although
women in all treatment groups (including placebo) reported
more adverse events than men. The most frequent adverse
event was somnolence (women: 11.1% for 40/30 mg, 8.5% for
20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4%
for 20/15 mg, 4.2% for placebo). CONCLUSION: Suvorexant was
generally effective and well-tolerated in both women and men
with insomnia. ClinicalTrials.gov trial registration
numbers: NCT01097616, NCT01097629, NCT01021813.},
Doi = {10.1007/s00213-017-4573-1},
Key = {fds325519}
}
@article{fds324864,
Author = {Nadler, JW and Evans, JL and Fang, E and Preud'Homme, XA and Daughtry,
RL and Chapman, JB and Bolognesi, MP and Attarian, DE and Wellman, SS and Krystal, AD},
Title = {A randomised trial of peri-operative positive airway
pressure for postoperative delirium in patients at risk for
obstructive sleep apnoea after regional anaesthesia with
sedation or general anaesthesia for joint
arthroplasty.},
Journal = {Anaesthesia},
Volume = {72},
Number = {6},
Pages = {729-736},
Year = {2017},
Month = {June},
url = {http://dx.doi.org/10.1111/anae.13833},
Abstract = {Previous pilot work has established an association between
obstructive sleep apnoea and the development of acute
postoperative delirium , but it remains unclear to what
extent this risk factor is modifiable in the 'real world'
peri-operative setting. In a single-blind randomised
controlled trial, 135 elderly surgical patients at risk for
obstructive sleep apnoea were randomly assigned to receive
peri-operative continuous positive airway pressure (CPAP) or
routine care. Of the 114 patients who completed the study,
21 (18.4%) experienced delirium. Delirium was equally common
in both groups: 21% (12 of 58 subjects) in the CPAP group
and 16% (9 of 56 subjects) in the routine care group (OR =
1.36 [95%CI 0.52-3.54], p = 0.53). Delirious subjects were
slightly older - mean (SD) age 68.9 (10.7) vs. 64.9 (8.2), p
= 0.07 - but had nearly identical pre-operative STOP-Bang
scores (4.19 (1.1) versus 4.27 (1.3), p = 0.79). Subjects in
the CPAP group used their devices for a median (IQR [range])
of 3 (0.25-5 [0-12]) nights pre-operatively (2.9 (0.1-4.8
[0.0-12.7]) hours per night) and 1 (0-2 [0-2]) nights
postoperatively (1.4 (0.0-5.1 [0.0-11.6]) hours per night).
Among the CPAP subjects, the residual pre-operative
apnoea-hypopnea index had a significant effect on delirium
severity (p = 0.0002). Although we confirm that apnoea is
associated with postoperative delirium, we did not find that
providing a short-course of auto-titrating CPAP affected its
likelihood or severity. Voluntary adherence to CPAP is
particularly poor during the initiation of
therapy.},
Doi = {10.1111/anae.13833},
Key = {fds324864}
}
@article{fds326867,
Author = {Carney, CE and Edinger, JD and Kuchibhatla, M and Lachowski, AM and Bogouslavsky, O and Krystal, AD and Shapiro, CM},
Title = {Cognitive Behavioral Insomnia Therapy for Those With
Insomnia and Depression: A Randomized Controlled Clinical
Trial.},
Journal = {Sleep},
Volume = {40},
Number = {4},
Year = {2017},
Month = {April},
url = {http://dx.doi.org/10.1093/sleep/zsx019},
Abstract = {STUDY OBJECTIVE: To compare cognitive behavioral therapy for
insomnia (CBT-I) + antidepressant medication (AD) against
treatments that target solely depression or solely insomnia.
DESIGN: A blinded, randomized split-plot experimental study.
SETTING: Two urban academic clinical centers. PARTICIPANTS:
107 participants (68% female, mean age 42 ± 11) with major
depressive disorder and insomnia. INTERVENTIONS:
Randomization was to one of three groups: antidepressant
(AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo
pill, or AD + 4-session sleep hygiene control (SH).
MEASUREMENTS AND RESULTS: Subjective sleep was assessed via
2 weeks of daily sleep diaries (use of medication was
covaried in all analyses); although there were no
statistically significant group differences detected, all
groups improved from baseline to posttreatment on subjective
sleep efficiency (SE) and total wake time (TWT) and the
effect sizes were large. Objective sleep was assessed via
overnight polysomnographic monitoring at baseline and
posttreatment; analyses revealed both CBT groups improved on
TWT (p = .03), but the AD + SH group worsened. There was no
statistically significant effect for PSG SE (p = .07). There
was a between groups medium effect observed for the AD + SH
and CBT + placebo group differences on diary TWT and both
PSG variables. All groups improved significantly from
baseline to posttreatment on the Hamilton Rating Scale for
Depression (HAMD-17); the groups did not differ.
CONCLUSIONS: Although all groups self-reported sleeping
better after treatment, only the CBT-I groups improved on
objective sleep, and AD + SH's sleep worsened. This suggests
that we should be treating sleep in those with depression
with an effective insomnia treatment and relying on
self-report obscures sleep worsening effects. All groups
improved on depression, even a group with absolutely no
depression-focused treatment component (CBT-I + placebo).
The depression effect in CBT-I only group has been reported
in other studies, suggesting that we should further
investigate the antidepressant properties of
CBT-I.},
Doi = {10.1093/sleep/zsx019},
Key = {fds326867}
}
@article{fds325881,
Author = {Edinger, JD and Manber, R and Buysse, DJ and Krystal, AD and Thase, ME and Gehrman, P and Fairholme, CP and Luther, J and Wisniewski,
S},
Title = {Are Patients with Childhood Onset of Insomnia and Depression
More Difficult to Treat Than Are Those with Adult Onsets of
These Disorders? A Report from the TRIAD
Study.},
Journal = {J Clin Sleep Med},
Volume = {13},
Number = {2},
Pages = {205-213},
Year = {2017},
Month = {February},
url = {http://dx.doi.org/10.5664/jcsm.6448},
Abstract = {STUDY OBJECTIVES: To determine if patients with childhood
onsets (CO) of both major depression and insomnia disorder
show blunted depression and insomnia treatment responses to
concurrent interventions for both disorders compared to
those with adult onsets (AO) of both conditions. METHODS:
This study was a secondary analysis of data obtained from a
multisite randomized clinical trial designed to test the
efficacy of combining a psychological/behavior insomnia
therapy with antidepressant medication to enhance depression
treatment outcomes in patients with comorbid major
depression and insomnia. This study included 27 adults with
CO of depression and insomnia and 77 adults with AO of both
conditions. They underwent a 16-week treatment including:
(1) a standardized two-step pharmacotherapy for depression
algorithm, consisting of escitalopram, sertraline, and
desvenlafaxine in a prescribed sequence; and (2) either
cognitive behavioral insomnia therapy (CBT-I) or a
quasi-desensitization control (CTRL) therapy. Main outcome
measures were the 17-item Hamilton Rating Scale for
Depression (HRSD-17) and the Insomnia Severity Index (ISI)
completed pre-treatment and every 2 weeks thereafter.
RESULTS: The AO and CO groups did not differ significantly
in regard to their pre-treatment HRSD-17 and ISI scores.
Mixed model analyses that adjusted for the number of
insomnia treatment sessions attended showed that the AO
group achieved significantly lower, subclinical scores on
the HRSD-17 and ISI than did the CO group by the time of
study exit. Moreover, a significant group by treatment arm
interaction suggested that HRSD-17 scores at study exit
remained significantly higher in the CO group receiving the
CTRL therapy than was the case for the participants in the
CO group receiving CBT-I. Greater proportions of the AO
group achieved a priori criteria for remission of insomnia
(49.3% vs. 29.2%, p = 0.04) and depression (45.5% vs. 29.6%,
p = 0.07) than did those in the CO group. CONCLUSIONS:
Patients with comorbid depression and insomnia who
experienced the first onset of both disorders in childhood
are less responsive to the treatments offered herein than
are those with adult onsets of these comorbid disorders.
Further research is needed to identify therapies that
enhance the depression and insomnia treatment responses of
those with childhood onsets of these two
conditions.},
Doi = {10.5664/jcsm.6448},
Key = {fds325881}
}
@article{fds325882,
Author = {Sateia, MJ and Buysse, DJ and Krystal, AD and Neubauer, DN and Heald,
JL},
Title = {Clinical Practice Guideline for the Pharmacologic Treatment
of Chronic Insomnia in Adults: An American Academy of Sleep
Medicine Clinical Practice Guideline.},
Journal = {J Clin Sleep Med},
Volume = {13},
Number = {2},
Pages = {307-349},
Year = {2017},
Month = {February},
url = {http://dx.doi.org/10.5664/jcsm.6470},
Abstract = {INTRODUCTION: The purpose of this guideline is to establish
clinical practice recommendations for the pharmacologic
treatment of chronic insomnia in adults, when such treatment
is clinically indicated. Unlike previous meta-analyses,
which focused on broad classes of drugs, this guideline
focuses on individual drugs commonly used to treat insomnia.
It includes drugs that are FDA-approved for the treatment of
insomnia, as well as several drugs commonly used to treat
insomnia without an FDA indication for this condition. This
guideline should be used in conjunction with other AASM
guidelines on the evaluation and treatment of chronic
insomnia in adults. METHODS: The American Academy of Sleep
Medicine commissioned a task force of four experts in sleep
medicine. A systematic review was conducted to identify
randomized controlled trials, and the Grading of
Recommendations Assessment, Development, and Evaluation
(GRADE) process was used to assess the evidence. The task
force developed recommendations and assigned strengths based
on the quality of evidence, the balance of benefits and
harms, and patient values and preferences. Literature
reviews are provided for those pharmacologic agents for
which sufficient evidence was available to establish
recommendations. The AASM Board of Directors approved the
final recommendations. RECOMMENDATIONS: The following
recommendations are intended as a guideline for clinicians
in choosing a specific pharmacological agent for treatment
of chronic insomnia in adults, when such treatment is
indicated. Under GRADE, a STRONG recommendation is one that
clinicians should, under most circumstances, follow. A WEAK
recommendation reflects a lower degree of certainty in the
outcome and appropriateness of the patient-care strategy for
all patients, but should not be construed as an indication
of ineffectiveness. GRADE recommendation strengths do not
refer to the magnitude of treatment effects in a particular
patient, but rather, to the strength of evidence in
published data. Downgrading the quality of evidence for
these treatments is predictable in GRADE, due to the funding
source for most pharmacological clinical trials and the
attendant risk of publication bias; the relatively small
number of eligible trials for each individual agent; and the
observed heterogeneity in the data. The ultimate judgment
regarding propriety of any specific care must be made by the
clinician in light of the individual circumstances presented
by the patient, available diagnostic tools, accessible
treatment options, and resources. We suggest that clinicians
use suvorexant as a treatment for sleep maintenance insomnia
(versus no treatment) in adults. (WEAK). We suggest that
clinicians use eszopiclone as a treatment for sleep onset
and sleep maintenance insomnia (versus no treatment) in
adults. (WEAK). We suggest that clinicians use zaleplon as a
treatment for sleep onset insomnia (versus no treatment) in
adults. (WEAK). We suggest that clinicians use zolpidem as a
treatment for sleep onset and sleep maintenance insomnia
(versus no treatment) in adults. (WEAK). We suggest that
clinicians use triazolam as a treatment for sleep onset
insomnia (versus no treatment) in adults. (WEAK). We suggest
that clinicians use temazepam as a treatment for sleep onset
and sleep maintenance insomnia (versus no treatment) in
adults. (WEAK). We suggest that clinicians use ramelteon as
a treatment for sleep onset insomnia (versus no treatment)
in adults. (WEAK). We suggest that clinicians use doxepin as
a treatment for sleep maintenance insomnia (versus no
treatment) in adults. (WEAK). We suggest that clinicians not
use trazodone as a treatment for sleep onset or sleep
maintenance insomnia (versus no treatment) in adults.
(WEAK). We suggest that clinicians not use tiagabine as a
treatment for sleep onset or sleep maintenance insomnia
(versus no treatment) in adults. (WEAK). We suggest that
clinicians not use diphenhydramine as a treatment for sleep
onset and sleep maintenance insomnia (versus no treatment)
in adults. (WEAK). We suggest that clinicians not use
melatonin as a treatment for sleep onset or sleep
maintenance insomnia (versus no treatment) in adults.
(WEAK). We suggest that clinicians not use tryptophan as a
treatment for sleep onset or sleep maintenance insomnia
(versus no treatment) in adults. (WEAK). We suggest that
clinicians not use valerian as a treatment for sleep onset
or sleep maintenance insomnia (versus no treatment) in
adults. (WEAK).},
Doi = {10.5664/jcsm.6470},
Key = {fds325882}
}
@article{fds323739,
Author = {Ohayon, M and Wickwire, EM and Hirshkowitz, M and Albert, SM and Avidan,
A and Daly, FJ and Dauvilliers, Y and Ferri, R and Fung, C and Gozal, D and Hazen, N and Krystal, A and Lichstein, K and Mallampalli, M and Plazzi,
G and Rawding, R and Scheer, FA and Somers, V and Vitiello,
MV},
Title = {National Sleep Foundation's sleep quality recommendations:
first report.},
Journal = {Sleep Health},
Volume = {3},
Number = {1},
Pages = {6-19},
Year = {2017},
Month = {February},
url = {http://dx.doi.org/10.1016/j.sleh.2016.11.006},
Abstract = {OBJECTIVES: To provide evidence-based recommendations and
guidance to the public regarding indicators of good sleep
quality across the life-span. METHODS: The National Sleep
Foundation assembled a panel of experts from the sleep
community and representatives appointed by stakeholder
organizations (Sleep Quality Consensus Panel). A systematic
literature review identified 277 studies meeting inclusion
criteria. Abstracts and full-text articles were provided to
the panelists for review and discussion. A modified Delphi
RAND/UCLA Appropriateness Method with 3 rounds of voting was
used to determine agreement. RESULTS: For most of the sleep
continuity variables (sleep latency, number of awakenings
>5minutes, wake after sleep onset, and sleep efficiency),
the panel members agreed that these measures were
appropriate indicators of good sleep quality across the
life-span. However, overall, there was less or no consensus
regarding sleep architecture or nap-related variables as
elements of good sleep quality. CONCLUSIONS: There is
consensus among experts regarding some indicators of sleep
quality among otherwise healthy individuals. Education and
public health initiatives regarding good sleep quality will
require sustained and collaborative efforts from multiple
stakeholders. Future research should explore how sleep
architecture and naps relate to sleep quality. Implications
and limitations of the consensus recommendations are
discussed.},
Doi = {10.1016/j.sleh.2016.11.006},
Key = {fds323739}
}
@article{fds323881,
Author = {Krystal, AD and Prather, AA},
Title = {Should Internet Cognitive Behavioral Therapy for Insomnia Be
the Primary Treatment Option for Insomnia?: Toward Getting
More SHUTi.},
Journal = {Jama Psychiatry},
Volume = {74},
Number = {1},
Pages = {15-16},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2016.3431},
Doi = {10.1001/jamapsychiatry.2016.3431},
Key = {fds323881}
}
@article{fds323561,
Author = {McCall, WV and Benca, RM and Rosenquist, PB and Riley, MA and McCloud,
L and Newman, JC and Case, D and Rumble, M and Krystal,
AD},
Title = {Hypnotic Medications and Suicide: Risk, Mechanisms,
Mitigation, and the FDA.},
Journal = {American Journal of Psychiatry},
Volume = {174},
Number = {1},
Pages = {18-25},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.1176/appi.ajp.2016.16030336},
Abstract = {OBJECTIVE: Insomnia is associated with increased risk for
suicide. The Food and Drug Administration (FDA) has mandated
that warnings regarding suicide be included in the
prescribing information for hypnotic medications. The
authors conducted a review of the evidence for and against
the claim that hypnotics increase the risk of suicide.
METHOD: This review focused on modern, FDA-approved
hypnotics, beginning with the introduction of
benzodiazepines, limiting its findings to adults. PubMed and
Web of Science were searched, crossing the terms "suicide"
and "suicidal" with each of the modern FDA-approved
hypnotics. The FDA web site was searched for postmarketing
safety reviews, and the FDA was contacted with requests to
provide detailed case reports for hypnotic-related suicide
deaths reported through its Adverse Event Reporting System.
RESULTS: Epidemiological studies show that hypnotics are
associated with an increased risk for suicide. However, none
of these studies adequately controlled for depression or
other psychiatric disorders that may be linked with
insomnia. Suicide deaths have been reported from
single-agent hypnotic overdoses. A separate concern is that
benzodiazepine receptor agonist hypnotics can cause
parasomnias, which in rare cases may lead to suicidal
ideation or suicidal behavior in persons who were not known
to be suicidal. On the other hand, ongoing research is
testing whether treatment of insomnia may reduce suicidality
in adults with depression. CONCLUSIONS: The review findings
indicate that hypnotic medications are associated with
suicidal ideation. Future studies should be designed to
assess whether increases in suicidality result from CNS
impairments from a given hypnotic medication or whether such
medication decreases suicidality because of improvements in
insomnia.},
Doi = {10.1176/appi.ajp.2016.16030336},
Key = {fds323561}
}
@article{fds327315,
Author = {Bathgate, CJ and Edinger, JD and Krystal, AD},
Title = {Insomnia Patients With Objective Short Sleep Duration Have a
Blunted Response to Cognitive Behavioral Therapy for
Insomnia.},
Journal = {Sleep},
Volume = {40},
Number = {1},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.1093/sleep/zsw012},
Abstract = {STUDY OBJECTIVES: This study examined whether individuals
with insomnia and objective short sleep duration <6 h, a
subgroup with greater risks of adverse health outcomes,
differ in their response to cognitive-behavioral therapy for
insomnia (CBT-I) when compared to individuals with insomnia
and normal sleep duration ≥6 h. METHODS: Secondary
analyses of a randomized, clinical trial with 60 adult
participants (n = 31 women) from a single academic medical
center. Outpatient treatment lasted 8 weeks, with a final
follow-up conducted at 6 months. Mixed-effects models
controlling for age, sex, CBT-I treatment group assignment,
and treatment provider examined sleep parameters gathered
via actigraphy, sleep diaries, and an Insomnia Symptom
Questionnaire (ISQ) across the treatment and follow-up
period. RESULTS: Six months post-CBT-I treatment,
individuals with insomnia and normal sleep duration ≥6 h
fared significantly better on clinical improvement
milestones than did those with insomnia and short sleep
duration <6 h. Specifically, individuals with insomnia and
normal sleep duration had significantly higher insomnia
remission (ISQ < 36.5; χ2[1, N = 60] = 44.72, p < .0001),
more normative sleep efficiency (SE) on actigraphy (SE >
80%; χ2[1, N = 60] = 21, p < .0001), normal levels of
middle of the night wake after sleep onset (MWASO) <31
minutes (χ2[1, N = 60] = 37.85, p < .0001), and a >50%
decline in MWASO (χ2[1, N = 60] = 60, p < .0001) compared
to individuals with insomnia and short sleep duration.
Additionally, those with insomnia and normal sleep duration
had more success decreasing their total wake time (TWT) at
the 6-month follow-up compared to those with insomnia and
short sleep duration (χ2[2, N = 60] = 44.1, p < .0001).
Receiver-operating characteristic curve analysis found that
using a 6-h cutoff with actigraphy provided a 95.7%
sensitivity and 91.9% specificity for determining insomnia
remission, with the area under the curve = 0.986.
CONCLUSIONS: Findings suggest that individuals with insomnia
and objective short sleep duration <6 h are significantly
less responsive to CBT-I than those with insomnia and normal
sleep duration ≥6 h. Using an actigraphy TST cutoff of 6
hours to classify sleep duration groups was highly accurate
and provided good discriminant value for determining
insomnia remission.},
Doi = {10.1093/sleep/zsw012},
Key = {fds327315}
}
@article{fds327316,
Author = {Krystal, AD and Preud'homme, XA},
Title = {Double-Blind, Placebo-Controlled, Crossover Study of
Armodafinil Treatment of Daytime Sleepiness Associated With
Treated Nocturia.},
Journal = {Sleep},
Volume = {40},
Number = {1},
Year = {2017},
Month = {January},
url = {http://dx.doi.org/10.1093/sleep/zsw020},
Abstract = {STUDY OBJECTIVES: Nocturia, voids which disturb sleep, is
the most common cause of awakenings and is associated with
daytime sleepiness. Because the standard treatments for the
most common causes of nocturia are relatively ineffective,
many treated patients with nocturia are left with residual
sleepiness. We carried out this pilot study to evaluate the
potential of armodafinil to be an effective means of
addressing the sleepiness that persists in many nocturia
patients, despite their receiving standard therapy. METHODS:
This was a double-blind, placebo-controlled, crossover study
carried out in 28 patients with nocturia who were receiving
standard clinical therapy for their nocturia and who had an
Epworth Sleepiness Scale (ESS) score of at least 10.
Subjects received 4 weeks of both armodafinil (150-250 mg)
and placebo with order randomized. RESULTS: Armodafinil led
to statistically significant improvement in sleepiness
compared to placebo as indicated by the ESS (the primary
outcome; p < .002) as well as the Clinical Global Impression
of Improvement in Sleepiness scale (key secondary outcome; p
= .01). Armodafinil did not increase nocturic events or
significantly increase adverse effects versus placebo.
CONCLUSIONS: This pilot study, the first double-blind,
placebo-controlled trial assessing whether a wake-promoting
therapy can improve residual daytime sleepiness in patients
with treated nocturia, indicates the promise of armodafinil
for addressing this residual sleepiness and provides impetus
to carry out a large-scale study to definitively evaluate
whether armodafinil is an effective therapy for the many
patients with nocturia who experience daytime sleepiness
that persists, despite their receiving standard therapy for
this condition.},
Doi = {10.1093/sleep/zsw020},
Key = {fds327316}
}
@article{fds322150,
Author = {Lunsford-Avery, JR and Krystal, AD and Kollins,
SH},
Title = {Sleep disturbances in adolescents with ADHD: A systematic
review and framework for future research.},
Journal = {Clin Psychol Rev},
Volume = {50},
Pages = {159-174},
Year = {2016},
Month = {December},
url = {http://dx.doi.org/10.1016/j.cpr.2016.10.004},
Abstract = {BACKGROUND: Biological mechanisms underlying symptom and
prognostic heterogeneity in Attention-Deficit/Hyperactivity
Disorder (ADHD) are unclear. Sleep impacts neurocognition
and daytime functioning and is disrupted in ADHD, yet little
is known about sleep in ADHD during adolescence, a period
characterized by alterations in sleep, brain structure, and
environmental demands as well as diverging ADHD
trajectories. METHODS: A systematic review identified
studies published prior to August 2016 assessing sleep in
adolescents (aged 10-19years) with ADHD or participating in
population-based studies measuring ADHD symptoms. RESULTS:
Twenty-five studies were identified (19 subjective report, 6
using actigraphy/polysomnography). Findings are mixed but
overall suggest associations between sleep disturbances and
1) ADHD symptoms in the population and 2) poorer clinical,
neurocognitive, and functional outcomes among adolescents
with ADHD. Common limitations of studies included small or
non-representative samples, non-standardized sleep measures,
and cross-sectional methodology. CONCLUSIONS: Current data
on sleep in adolescent ADHD are sparse and limited by
methodological concerns. Future studies are critical for
clarifying a potential role of sleep in contributing to
heterogeneity of ADHD presentation and prognosis. Potential
mechanisms by which sleep disturbances during adolescence
may contribute to worsened symptom severity and persistence
of ADHD into adulthood and an agenda to guide future
research are discussed.},
Doi = {10.1016/j.cpr.2016.10.004},
Key = {fds322150}
}
@article{fds322849,
Author = {Ptáǒek, LJ and Fu, Y-H and Krystal, AD},
Title = {Sleep and Mood: Chicken or Egg?},
Journal = {Biol Psychiatry},
Volume = {80},
Number = {11},
Pages = {810-811},
Year = {2016},
Month = {December},
url = {http://dx.doi.org/10.1016/j.biopsych.2016.09.012},
Doi = {10.1016/j.biopsych.2016.09.012},
Key = {fds322849}
}
@article{fds350258,
Author = {Krystal, A and Attarian, H},
Title = {Sleep Medications and Women: a Review of Issues to Consider
for Optimizing the Care of Women with Sleep
Disorders},
Journal = {Current Sleep Medicine Reports},
Volume = {2},
Number = {4},
Pages = {218-222},
Year = {2016},
Month = {December},
url = {http://dx.doi.org/10.1007/s40675-016-0060-1},
Abstract = {Certain medications exhibit sex-specific pharmacological
profiles. It is, therefore, imperative to understand their
unique pharmacokinetic properties to optimize women’s
health. Two such medications that are commonly used in sleep
medicine are zolpidem and modafinil/armodafinil. The first
is a sedative hypnotic while the latter, in both its
incarnations, a wake-promoting agent. The slower clearance
of these medications and higher serum concentrations after
dosing in women are independent of weight and have to do
with the impact of estrogen on the liver enzymes involved in
the metabolism of these medications. Below, we summarize and
discuss the data that is available on the sex-specific
dosing of zolpidem, which in women, by FDA recommendations,
is half of what is recommended in men. We also discuss the
reasons behind the interaction of hormonal birth control and
modafinil/armodafinil and rate of contraceptive failure when
hormonal birth control is used with this wake-promoting
agent.},
Doi = {10.1007/s40675-016-0060-1},
Key = {fds350258}
}
@article{fds322149,
Author = {Jacobsen, JPR and Krystal, AD and Krishnan, KRR and Caron,
MG},
Title = {Adjunctive 5-Hydroxytryptophan Slow-Release for
Treatment-Resistant Depression: Clinical and Preclinical
Rationale.},
Journal = {Trends Pharmacol Sci},
Volume = {37},
Number = {11},
Pages = {933-944},
Year = {2016},
Month = {November},
url = {http://dx.doi.org/10.1016/j.tips.2016.09.001},
Abstract = {Serotonin transporter (SERT) inhibitors treat depression by
elevating brain extracellular 5-hydroxytryptamine (5-HTExt).
However, only one-third of patients respond adequately.
Treatment-resistant depression (TRD) is a major unmet need.
Interestingly, elevating 5-HTExt beyond what is achieved by
a SERT inhibitor appears to treat TRD. Adjunctive
administration of 5-hydroxytryptophan (5-HTP) safely
elevates 5-HTExt beyond the SERT inhibitor effect in humans;
however, 5-HTP cannot be a clinically viable drug because of
its poor pharmacokinetics. A slow-release (SR) delivery mode
would be predicted to overcome the pharmacokinetic
limitations of 5-HTP, substantially enhancing the
pharmacological action and transforming 5-HTP into a
clinically viable drug. Animal studies bear out this
prediction. Thus, adjunct 5-HTP SR could be an important new
treatment for TRD. Here, we review the clinical and
preclinical evidence for this treatment.},
Doi = {10.1016/j.tips.2016.09.001},
Key = {fds322149}
}
@article{fds322851,
Author = {Carlezon, WA and Krystal, AD},
Title = {Kappa-Opioid Antagonists for Psychiatric Disorders: From
Bench to Clinical Trials.},
Journal = {Depress Anxiety},
Volume = {33},
Number = {10},
Pages = {895-906},
Year = {2016},
Month = {October},
url = {http://dx.doi.org/10.1002/da.22500},
Abstract = {Kappa-opioid receptor (KOR) antagonists are currently being
considered for the treatment of a variety of
neuropsychiatric conditions, including depressive, anxiety,
and substance abuse disorders. A general ability to mitigate
the effects of stress, which can trigger or exacerbate these
conditions, may explain their putative efficacy across such
a broad array of conditions. The discovery of their
potentially therapeutic effects evolved from preclinical
research designed to characterize the molecular mechanisms
by which experience causes neuroadaptations in the nucleus
accumbens (NAc), a key element of brain reward circuitry.
This research established that exposure to drugs of abuse or
stress increases the activity of the transcription factor
CREB (cAMP response element binding protein) in the NAc,
which leads to elevated expression of the opioid peptide
dynorphin that in turn causes core signs of depressive- and
anxiety-related disorders. Disruption of KORs-the endogenous
receptors for dynorphin-produces antidepressant- and
anxiolytic-like actions in screening procedures that
identify standard drugs of these classes, and reduces stress
effects in tests used to study addiction and stress-related
disorders. Although interest in this target is high,
prototypical KOR antagonists have extraordinarily persistent
pharmacodynamic effects that complicate clinical trials. The
development of shorter acting KOR antagonists together with
more rapid designs for clinical trials may soon provide
insight on whether these drugs are efficacious as would be
predicted by preclinical work. If successful, KOR
antagonists would represent a unique example in psychiatry
where the therapeutic mechanism of a drug class is
understood before it is shown to be efficacious in
humans.},
Doi = {10.1002/da.22500},
Key = {fds322851}
}
@article{fds319928,
Author = {Herring, WJ and Connor, KM and Snyder, E and Snavely, DB and Zhang, Y and Hutzelmann, J and Matzura-Wolfe, D and Benca, RM and Krystal, AD and Walsh, JK and Lines, C and Roth, T and Michelson,
D},
Title = {Suvorexant in Patients with Insomnia: Pooled Analyses of
Three-Month Data from Phase-3 Randomized Controlled Clinical
Trials.},
Journal = {J Clin Sleep Med},
Volume = {12},
Number = {9},
Pages = {1215-1225},
Year = {2016},
Month = {September},
url = {http://dx.doi.org/10.5664/jcsm.6116},
Abstract = {STUDY OBJECTIVES: Suvorexant is an orexin receptor
antagonist approved for treating insomnia at a maximum dose
of 20 mg. Phase-3 trials evaluated two age-adjusted
(non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg
with the primary focus on 40/30 mg. We report here results
from pooled analyses of the 20/15 mg dose-regime, which was
evaluated as a secondary objective in the trials. METHODS:
Prespecified analysis of pooled data from two identical
randomized, double-blind, placebo-controlled,
parallel-group, 3-month trials in non-elderly (18-64 years)
and elderly (≥ 65 years) patients with insomnia. Patients
were randomized to suvorexant 20/15 mg (non-elderly/elderly),
suvorexant 40/30 mg (non-elderly/elderly), or placebo; by
design, fewer patients were randomized to 20/15 mg. Efficacy
was assessed by self-reported and polysomnography (PSG;
subset of patients) sleep maintenance and onset endpoints.
RESULTS: Suvorexant 20/15 mg (N = 493 treated) was effective
compared to placebo (N = 767 treated) on patient-reported
and PSG sleep maintenance and onset endpoints at Night-1
(PSG endpoints) / Week-1 (subjective endpoints), Month-1 and
Month-3, except for effects on PSG sleep onset at Month-3.
Suvorexant 20/15 mg was generally well tolerated, with 3% of
patients discontinuing due to adverse events over 3 months
vs. 5.2% on placebo. Somnolence was the most common adverse
event (6.7% vs. 3.3% for placebo). There was no systematic
evidence of rebound or withdrawal signs or symptoms when
suvorexant was discontinued after 3 months of nightly use.
CONCLUSIONS: Suvorexant 20/15 mg improved sleep onset and
maintenance over 3 months of nightly treatment and was
generally safe and well tolerated. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov trial registration numbers:
NCT01097616, NCT01097629.},
Doi = {10.5664/jcsm.6116},
Key = {fds319928}
}
@article{fds325520,
Author = {Bathgate, CJ and Edinger, JD and Krystal, AD},
Title = {Insomnia Patients with Objective Short Sleep Duration have a
Blunted Response to Cognitive Behavioral Therapy for
Insomnia.},
Journal = {Sleep},
Year = {2016},
Month = {September},
Abstract = {STUDY OBJECTIVES: This study examined whether individuals
with insomnia and objective short sleep duration <6h, a
subgroup with greater risks of adverse health outcomes,
differ in their response to cognitive behavioral therapy for
insomnia (CBT-I) when compared to individuals with insomnia
and normal sleep duration >6h. METHODS: Secondary analyses
of a randomized, clinical trial with 60 adults participants
(n=31 women) from a single academic medical center.
Outpatient treatment lasted 8 weeks, with a final follow-up
conducted at 6 months. Mixed-effects models controlling for
age, sex, CBT-I treatment group assignment, and treatment
provider examined sleep parameters gathered via actigraphy,
sleep diaries, and an Insomnia Symptom Questionnaire (ISQ)
across the treatment and follow-up period. RESULTS: Six
months post-CBT-I treatment, individuals with insomnia and
normal sleep duration >6h fared significantly better on
clinical improvement milestones than did those with insomnia
and short sleep duration <6h. Specifically, individuals with
insomnia and normal sleep duration had significantly higher
insomnia remission [ISQ<36.5; X2(1, N=60) =44.72, P<.0001],
more normative sleep efficiency on actigraphy [SE>80%; X2(1,
N=60) =21, P<.0001], normal level of MWASO <31 minutes
[X2(1, N=60) =37.85, P<.0001], and a >50% decline in MWASO
[X2(1, N=60) =60, P<.0001] compared to individuals with
insomnia and short sleep duration. Additionally, those with
insomnia and normal sleep duration had more success
decreasing their TWT at the 6-month follow-up compared to
those with insomnia and short sleep duration [X2(2, N=60)
=44.1, P<.0001]. Receiver operating characteristic curve
analysis found that using a 6-h cutoff with actigraphy
provided a 95.7% sensitivity and 91.9% specificity for
determining insomnia remission, with the area under the
curve = 0.986. CONCLUSIONS: Findings suggest that
individuals with insomnia and objective short sleep duration
<6h are significantly less responsive to CBT-I than those
with insomnia and normal sleep duration >6h. Using an
actigraphy TST cutoff of 6 hours to classify sleep duration
groups was highly accurate and provided good discriminant
value for determining insomnia remission.},
Key = {fds325520}
}
@article{fds325521,
Author = {Krystal, AD and Preud'homme, XA},
Title = {DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS-OVER, STUDY OF
ARMODAFINIL TREATMENT OF DAYTIME SLEEPINESS ASSOCIATED WITH
TREATED NOCTURIA.},
Journal = {Sleep},
Year = {2016},
Month = {September},
Abstract = {STUDY OBJECTIVES: Nocturia, voids which disturb sleep, is
the most common cause of awakenings and is associated with
daytime sleepiness. Because the standard treatments for the
most common causes of nocturia are relatively ineffective,
many treated patients with nocturia are left with residual
sleepiness. We carried out this pilot study to evaluate the
potential of Armodafinil to be an effective means of
addressing the sleepiness that persists in many nocturia
patients despite their receiving standard therapy. METHODS:
This was a double-blind, placebo-controlled, cross-over
study carried out in 28 patients with nocturia who were
receiving standard clinical therapy for their nocturia and
who had an Epworth Sleepiness Scale Score (ESS) of at least
10. Subjects received 4 weeks of both armodafinil (150-250
mg) and placebo with order randomized. RESULTS: Armodafinil
led to statistically significant improvement in sleepiness
compared with placebo as indicated by the ESS (the primary
outcome) (p<0.002) as well as the Clinical Global Impression
of Improvement in Sleepiness scale (key secondary outcome)
(p=0.01). Armodafinil did not increase nocturic events or
significantly increase adverse effects vs placebo.
CONCLUSIONS: This pilot study, the first double-blind,
placebo-controlled trial assessing whether a wake-promoting
therapy can improve residual daytime sleepiness in patients
with treated nocturia, indicates the promise of armodafinil
for addressing this residual sleepiness and provides impetus
to carry out a large-scale study to definitively evaluate
whether armodafinil is an effective therapy for the many
patients with nocturia who experience daytime sleepiness
that persists despite their receiving standard therapy for
this condition.},
Key = {fds325521}
}
@article{fds322852,
Author = {Krystal, AD and Mittoux, A and Meisels, P and Baker,
RA},
Title = {Effects of Adjunctive Brexpiprazole on Sleep Disturbances in
Patients With Major Depressive Disorder: An Open-Label,
Flexible-Dose, Exploratory Study.},
Journal = {Prim Care Companion Cns Disord},
Volume = {18},
Number = {5},
Year = {2016},
Month = {September},
url = {http://dx.doi.org/10.4088/PCC.15m01914},
Abstract = {BACKGROUND: Brexpiprazole is a serotonin-dopamine activity
modulator. We evaluated the effects of adjunctive treatment
with brexpiprazole on sleep disturbances in patients with
DSM-IV-TR major depressive disorder (MDD) and inadequate
response to antidepressant treatment. METHODS: This study
was conducted between September 27, 2013, and August 19,
2014. Patients with inadequate response to antidepressant
treatment and sleep disturbances continued treatment with
their current antidepressant for 2 weeks. Patients still
having inadequate response and sleep efficiency less than
85% measured by baseline polysomnography (PSG) received
8-week open-label treatment with their current
antidepressant treatment and adjunctive brexpiprazole
(target dose: 3 mg/d). Assessments included PSG recordings
and scales of insomnia severity, depressive symptoms, and
daytime alertness and functioning. Changes from baseline to
week 8 were analyzed. RESULTS: Forty-four patients were
treated. Improvements (P < .05) measured by PSG and
Consensus Sleep Diary for Morning, respectively, were
observed in sleep efficiency (10.4 and 15.4 percentage
points), total sleep time (49.0 and 84.5 min), sleep onset
latency (-19.7 and -42.6 min), wake-time after sleep onset
(-26.4 and -48.0 min), and latency to persistent sleep
(-24.9 min, PSG only). Insomnia Severity Index (ISI) total
score was improved (-9.2), as was daytime sleepiness (-2.1)
as measured by the Epworth Sleepiness Scale (ESS) total
score and morning sleepiness (-9.2) as measured by the
Bond-Lader Visual Analog Scale (all P < .05). Reaction time
was slightly decreased (-0.2 sec-1) by treatment (P < .05).
Depressive symptoms improved (Montgomery-Asberg Depression
Rating Scale [MADRS]: -16.0 and Clinical Global
Impressions-Severity [CGI-S]: -1.8), as did functioning
(-8.4) assessed by the Massachusetts General
Hospital-Cognitive and Physical Functioning Questionnaire
(all P < .05). Improvements in depressive symptoms were
dependent on sleep (as assessed by ISI) (P < .0001) and
improvements in daytime alertness (as assessed by ESS) were
dependent on improvements in ISI (P = .009). No new safety
concerns were observed compared to previous brexpiprazole
studies. CONCLUSIONS: In patients with inadequate response
to antidepressant treatment and sleep disturbances treated
with adjunctive brexpiprazole, physiologic measures of sleep
and daytime alertness were improved. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01942733.},
Doi = {10.4088/PCC.15m01914},
Key = {fds322852}
}
@article{fds322853,
Author = {Blanco, MB and Dausmann, KH and Faherty, SL and Klopfer, P and Krystal,
AD and Schopler, R and Yoder, AD},
Title = {Hibernation in a primate: does sleep occur?},
Journal = {Royal Society Open Science},
Volume = {3},
Number = {8},
Pages = {160282},
Year = {2016},
Month = {August},
url = {http://dx.doi.org/10.1098/rsos.160282},
Abstract = {During hibernation, critical physiological processes are
downregulated and thermogenically induced arousals are
presumably needed periodically to fulfil those physiological
demands. Among the processes incompatible with a hypome
tabolic state is sleep. However, one hibernating primate,
the dwarf lemur Cheirogaleus medius, experiences rapid eye
movement (REM)-like states during hibernation, whenever
passively reaching temperatures above 30°C, as occurs when
it hibernates in poorly insulated tree hollows under
tropical conditions. Here, we report electroencephalographic
(EEG) recordings, temperature data and metabolic rates from
two related species (C. crossleyi and C. sibreei),
inhabiting high-altitude rainforests and hibernating
underground, conditions that mirror, to some extent, those
experienced by temperate hibernators. We compared the
physiology of hibernation and spontaneous arousals in these
animals to C. medius, as well as the much more distantly
related non-primate hibernators, such as Arctic,
golden-mantled and European ground squirrels. We observed a
number of commonalities with non-primate temperate
hibernators including: (i) monotonous ultra-low voltage EEG
during torpor bouts in these relatively cold-weather
hibernators, (ii) the absence of sleep during torpor bouts,
(iii) the occurrence of spontaneous arousals out of torpor,
during which sleep regularly occurred, (iv) relatively high
early EEG non-REM during the arousal, and (v) a gradual
transition to the torpid EEG state from non-REM sleep.
Unlike C. medius, our study species did not display
sleep-like states during torpor bouts, but instead
exclusively exhibited them during arousals. During these
short euthermic periods, non-REM as well as REM sleep-like
stages were observed. Differences observed between these two
species and their close relative, C. medius, for which data
have been published, presumably reflect differences in
hibernaculum temperature.},
Doi = {10.1098/rsos.160282},
Key = {fds322853}
}
@article{fds319923,
Author = {Krystal, JH and Abi-Dargham, A and Akbarian, S and Arnsten, AFT and Barch, DM and Bearden, CE and Braff, DL and Brown, ES and Bullmore, ET and Carlezon, WA and Carter, CS and Cook, EH and Daskalakis, ZJ and DiLeone,
RJ and Duman, RS and Grace, AA and Hariri, AR and Harrison, PJ and Hiroi,
N and Kenny, PJ and Kleinman, JE and Krystal, AD and Lewis, DA and Lipska,
BK and Marder, SR and Mason, GF and Mathalon, DH and McClung, CA and McDougle, CJ and McIntosh, AM and McMahon, FJ and Mirnics, K and Monteggia, LM and Narendran, R and Nestler, EJ and Neumeister, A and O'Donovan, MC and Öngür, D and Pariante, CM and Paulus, MP and Pearlson, G and Phillips, ML and Pine, DS and Pizzagalli, DA and Pletnikov, MV and Ragland, JD and Rapoport, JL and Ressler, KJ and Russo, SJ and Sanacora, G and Sawa, A and Schatzberg, AF and Shaham, Y and Shamay-Tsoory, SG and Sklar, P and State, MW and Stein, MB and Strakowski, SM and Taylor, SF and Turecki, G and Turetsky, BI and Weissman, MM and Zachariou, V and Zarate, CA and Zubieta,
J-K},
Title = {Constance E. Lieber, Theodore R. Stanley, and the Enduring
Impact of Philanthropy on Psychiatry Research.},
Journal = {Biol Psychiatry},
Volume = {80},
Number = {2},
Pages = {84-86},
Year = {2016},
Month = {July},
url = {http://dx.doi.org/10.1016/j.biopsych.2016.05.004},
Doi = {10.1016/j.biopsych.2016.05.004},
Key = {fds319923}
}
@article{fds319924,
Author = {Bathgate, CJ and Edinger, JD and Wyatt, JK and Krystal,
AD},
Title = {Objective but Not Subjective Short Sleep Duration Associated
with Increased Risk for Hypertension in Individuals with
Insomnia.},
Journal = {Sleep},
Volume = {39},
Number = {5},
Pages = {1037-1045},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.5665/sleep.5748},
Abstract = {STUDY OBJECTIVES: To examine the relationship between
hypertension prevalence in individuals with insomnia who
have short total sleep duration < 6 h or sleep duration ≥
6 h, using both objective and subjective measures of total
sleep duration. METHODS: Using a cross-sectional,
observational design, 255 adult volunteers (n = 165 women;
64.7%) meeting current diagnostic criteria for insomnia
disorder (MAge = 46.2 y, SDAge = 13.7 y) participated in
this study at two large university medical centers. Two
nights of polysomnography, 2 w of sleep diaries,
questionnaires focused on sleep, medical, psychological, and
health history, including presence/absence of hypertension
were collected. Logistic regressions assessed the odds
ratios of hypertension among persons with insomnia with
short sleep duration < 6 h compared to persons with insomnia
with a sleep duration ≥ 6 h, measured both objectively and
subjectively. RESULTS: Consistent with previous studies
using objective total sleep duration, individuals with
insomnia and short sleep duration < 6 h were associated with
a 3.59 increased risk of reporting hypertension as a current
medical problem as compared to individuals with insomnia
with sleep duration ≥ 6 h. Increased risk for hypertension
was independent of major confounding factors frequently
associated with insomnia or hypertension. No significant
risk was observed using subjectively determined total sleep
time groups. Receiver operating characteristic curve
analysis found that the best balance of sensitivity and
specificity using subjective total sleep time was at a 6-h
cutoff, but the area under the receiver operating
characteristic curve showed low accuracy and did not have
good discriminant value. CONCLUSIONS: Objectively measured
short sleep duration increased the odds of reporting
hypertension more than threefold after adjusting for
potential confounders; this relationship was not significant
for subjectively measured sleep duration. This research
supports emerging evidence that insomnia with objective
short sleep duration is associated with an increased risk of
comorbid hypertension.},
Doi = {10.5665/sleep.5748},
Key = {fds319924}
}
@article{fds319925,
Author = {Krystal, AD and Zammit, G},
Title = {The sleep effects of lurasidone: a placebo-controlled
cross-over study using a 4-h phase-advance model of
transient insomnia.},
Journal = {Hum Psychopharmacol},
Volume = {31},
Number = {3},
Pages = {206-216},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.1002/hup.2533},
Abstract = {BACKGROUND: Lurasidone, an atypical antipsychotic, is a
potent 5-HT7 antagonist and D2 , 5-HT2A antagonist, and
5-HT1A partial agonist. As such, lurasidone would be
expected to modulate sleep and circadian function but there
have been no human studies of the sleep effects of a 5-HT7
antagonist. The purpose of this study was to assess effects
of lurasidone on sleep. METHODS: This was a cross-over,
polysomnographic study involving 54 healthy volunteers who
underwent two treatment periods (order randomized) each
consisting of two nights in the laboratory: Night 1-lights
out at usual bedtime; Night 2-4-h advance of sleep phase and
randomization to either lurasidone 40 mg or placebo. The
next morning impairment testing was carried out. RESULTS:
Lurasidone significantly (p < 0.05) increased total
sleep time by an average of 28.4 min versus placebo,
decreased wake time after sleep onset and wake time after
the final awakening, and increased sleep efficiency. No
other effects were found. CONCLUSIONS: Lurasidone had a
sleep maintenance effect without effects on sleep onset,
rapid eye movement, or slow-wave sleep. Lurasidone is likely
to be beneficial to patients with disturbed sleep,
particularly those with sleep maintenance problems.
Copyright © 2016 John Wiley & Sons, Ltd.},
Doi = {10.1002/hup.2533},
Key = {fds319925}
}
@article{fds311654,
Author = {Krystal, JH and Pietrzak, RH and Rosenheck, RA and Cramer, JA and Vessicchio, J and Jones, KM and Huang, GD and Vertrees, JE and Collins,
J and Krystal, AD and Veterans Affairs Cooperative Study #504
Group},
Title = {Sleep disturbance in chronic military-related PTSD: clinical
impact and response to adjunctive risperidone in the
Veterans Affairs cooperative study #504.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {77},
Number = {4},
Pages = {483-491},
Year = {2016},
Month = {April},
ISSN = {0160-6689},
url = {http://dx.doi.org/10.4088/JCP.14m09585},
Abstract = {OBJECTIVE: Sleep disturbances are common among veterans with
chronic military-related posttraumatic stress disorder
(PTSD). This article reports the results of a multicenter
clinical trial that explored the clinical correlates of
reported sleep impairment in these veterans and tested the
impact of the second-generation antipsychotic risperidone
upon these symptoms. METHOD: This article reports secondary
analyses of a 24-week multicenter randomized
placebo-controlled trial of adjunctive risperidone in
patients with chronic military-related PTSD symptoms (n =
267, 97% male) who were symptomatic despite treatment with
antidepressants and other medications. The study was
conducted between February 2007 and February 2010. DSM-IV
PTSD diagnoses were made by using the Structured Clinical
Interview for DSM-IV-TR Axis I Disorders, Nonpatient
Edition. Sleep disturbances were assessed principally by
using the Pittsburgh Sleep Quality Index (PSQI) (primary
outcome measure). Analyses were conducted using bivariate
correlations and longitudinal mixed model regressions.
RESULTS: Eighty-eight percent of the patients in this study
had clinically significantly impaired sleep on the PSQI.
Severity of sleep disturbances correlated with PTSD symptom
severity as measured by the Clinician-Administered PTSD
Scale (CAPS) and reductions in multiple measures of quality
of life (Veterans RAND 36-item Health Survey [SF-36 V]
subscales, Boston Life Satisfaction Index). Risperidone
produced small but statistically significant effects on
total PSQI scores (main effect of drug: F1,228 = 4.57, P =
.034; drug-by-time interaction: F2,421 = 4.32, P = .014) and
severity of nightmares as assessed by the CAPS (main effect
of drug: F1,248 = 4.60, P = .033). The improvements in sleep
quality produced by risperidone correlated with reductions
in PTSD symptom severity and improvement in the mental
health subscale of the SF-36 V. CONCLUSIONS: This study
highlighted the near universality and significant negative
impact of severe disturbances in sleep quality in veterans
with chronic military-related PTSD who were partial
responders to standard pharmacotherapies. The modest
improvements in sleep quality produced by adjunctive
risperidone were correlated with limited reductions in PTSD
severity and improvements in quality of life. TRIAL
REGISTRATION: ClinicalTrials.gov identifier:
NCT00099983.},
Doi = {10.4088/JCP.14m09585},
Key = {fds311654}
}
@article{fds319926,
Author = {Krystal, AD and Sorscher, AJ},
Title = {Recognizing and managing insomnia in primary care and
specialty settings.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {77},
Number = {4},
Pages = {e471},
Year = {2016},
Month = {April},
url = {http://dx.doi.org/10.4088/JCP.15029wc1c},
Abstract = {Insomnia is a common feature of both medical and psychiatric
disorders. Whether as a symptom of an illness or as a
comorbid disorder, insomnia worsens patient outcomes related
to quality of life, functioning, workplace productivity, and
health care expenditures. This CME webcast covers how to
screen for insomnia in patients with both medical and mental
illnesses and how to develop a comprehensive treatment plan.
The authors also review evidence-based therapies for
insomnia, including psychological/behavioral interventions
and medications.},
Doi = {10.4088/JCP.15029wc1c},
Key = {fds319926}
}
@article{fds319927,
Author = {Morin, CM and Edinger, JD and Krystal, AD and Buysse, DJ and Beaulieu-Bonneau, S and Ivers, H},
Title = {Sequential psychological and pharmacological therapies for
comorbid and primary insomnia: study protocol for a
randomized controlled trial.},
Journal = {Trials},
Volume = {17},
Number = {1},
Pages = {118},
Year = {2016},
Month = {March},
url = {http://dx.doi.org/10.1186/s13063-016-1242-3},
Abstract = {BACKGROUND: Chronic insomnia is a prevalent disorder
associated with significant psychosocial, health, and
economic impacts. Cognitive behavioral therapies (CBTs) and
benzodiazepine receptor agonist (BzRA) medications are the
most widely supported therapeutic approaches for insomnia
management. However, few investigations have directly
compared their relative and combined benefits, and even
fewer have tested the benefits of sequential treatment for
those who do not respond to initial insomnia therapy.
Moreover, insomnia treatment studies have been limited by
small, highly screened study samples, fixed-dose, and
fixed-agent pharmacotherapy strategies that do not represent
usual clinical practices. This study will address these
limitations. METHODS/DESIGN: This is a two-site randomized
controlled trial, which will enroll 224 adults who meet the
criteria for a chronic insomnia disorder with or without
comorbid psychiatric disorders. Prospective participants
will complete clinical assessments and polysomnography and
then will be randomly assigned to first-stage therapy
involving either behavioral therapy (BT) or zolpidem.
Treatment outcomes will be assessed after 6 weeks, and
treatment remitters will be followed for the next 12 months
on maintenance therapy. Those not achieving remission will
be offered randomization to a second, 6-week treatment,
again involving either pharmacotherapy (zolpidem or
trazodone) or psychological therapy (BT or cognitive therapy
(CT)). All participants will be re-evaluated 12 weeks after
the protocol initiation and at 3-, 6-, 9-, and 12-month
follow-ups. Insomnia remission, defined categorically as a
score < 8 on the Insomnia Severity Index, a patient-reported
outcome, will serve as the primary endpoint for treatment
comparisons. Secondary outcomes will include sleep
parameters derived from daily sleep diaries and from
polysomnography, subjective measures of fatigue, mood,
quality of life, and functional impairments; and measures of
adverse events; dropout rates; and treatment acceptability.
Centrally trained therapists will administer therapies
according to manualized, albeit flexible, treatment
algorithms. DISCUSSION: This clinical trial will provide new
information about optimal treatment sequencing and will have
direct implication for the development of clinical
guidelines for managing chronic insomnia with and without
comorbid psychiatric conditions. TRIAL REGISTRATION:
ClinicalTrials.gov Identifier: NCT01651442 , Protocol
version 4, 20 April 2011, registered 26 June
2012.},
Doi = {10.1186/s13063-016-1242-3},
Key = {fds319927}
}
@article{fds281853,
Author = {Herring, WJ and Connor, KM and Ivgy-May, N and Snyder, E and Liu, K and Snavely, DB and Krystal, AD and Walsh, JK and Benca, RM and Rosenberg,
R and Sangal, RB and Budd, K and Hutzelmann, J and Leibensperger, H and Froman, S and Lines, C and Roth, T and Michelson,
D},
Title = {Suvorexant in Patients With Insomnia: Results From Two
3-Month Randomized Controlled Clinical Trials.},
Journal = {Biol Psychiatry},
Volume = {79},
Number = {2},
Pages = {136-148},
Year = {2016},
Month = {January},
ISSN = {0006-3223},
url = {http://dx.doi.org/10.1016/j.biopsych.2014.10.003},
Abstract = {BACKGROUND: Suvorexant is an orexin receptor antagonist for
treatment of insomnia. We report results from two pivotal
phase 3 trials. METHODS: Two randomized, double-blind,
placebo-controlled, parallel-group, 3-month trials in
nonelderly (18-64 years) and elderly (≥65 years) patients
with insomnia. Suvorexant doses of 40/30 mg
(nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were
evaluated. The primary focus was 40/30 mg, with fewer
patients randomized to 20/15 mg. There was an optional
3-month double-blind extension in trial 1. Each trial
included a 1-week, randomized, double-blind run-out after
double-blind treatment to assess withdrawal/rebound.
Efficacy was assessed at week 1, month 1, and month 3 by
patient-reported subjective total sleep time and time to
sleep onset and in a subset of patients at night 1, month 1,
and month 3 by polysomnography end points of wakefulness
after persistent sleep onset and latency to onset of
persistent sleep (LPS). One thousand twenty-one patients
were randomized in trial 1 and 1019 patients in trial 2.
RESULTS: Suvorexant 40/30 mg was superior to placebo on all
subjective and polysomnography end points at night 1/week 1,
month 1, and month 3 in both trials, except for LPS at month
3 in trial 2. Suvorexant 20/15 mg was superior to placebo on
subjective total sleep time and wakefulness after persistent
sleep onset at night 1/week 1, month 1, and month 3 in both
trials and at most individual time points for subjective
time to sleep onset and LPS in each trial. Both doses of
suvorexant were generally well tolerated, with <5% of
patients discontinuing due to adverse events over 3 months.
The results did not suggest the emergence of marked rebound
or withdrawal signs or symptoms when suvorexant was
discontinued. CONCLUSIONS: Suvorexant improved sleep onset
and maintenance over 3 months of nightly treatment and was
generally safe and well tolerated.},
Doi = {10.1016/j.biopsych.2014.10.003},
Key = {fds281853}
}
@article{fds327317,
Author = {Nunn, CL and Samson, DR and Krystal, AD},
Title = {Shining evolutionary light on human sleep and sleep
disorders.},
Journal = {Evolution, Medicine, and Public Health},
Volume = {2016},
Number = {1},
Pages = {227-243},
Year = {2016},
url = {http://dx.doi.org/10.1093/emph/eow018},
Abstract = {Sleep is essential to cognitive function and health in
humans, yet the ultimate reasons for sleep-i.e. 'why' sleep
evolved-remain mysterious. We integrate findings from human
sleep studies, the ethnographic record, and the ecology and
evolution of mammalian sleep to better understand sleep
along the human lineage and in the modern world. Compared to
other primates, sleep in great apes has undergone
substantial evolutionary change, with all great apes
building a sleeping platform or 'nest'. Further evolutionary
change characterizes human sleep, with humans having the
shortest sleep duration, yet the highest proportion of rapid
eye movement sleep among primates. These changes likely
reflect that our ancestors experienced fitness benefits from
being active for a greater portion of the 24-h cycle than
other primates, potentially related to advantages arising
from learning, socializing and defending against predators
and hostile conspecifics. Perspectives from evolutionary
medicine have implications for understanding sleep
disorders; we consider these perspectives in the context of
insomnia, narcolepsy, seasonal affective disorder, circadian
rhythm disorders and sleep apnea. We also identify how human
sleep today differs from sleep through most of human
evolution, and the implications of these changes for global
health and health disparities. More generally, our review
highlights the importance of phylogenetic comparisons in
understanding human health, including well-known links
between sleep, cognitive performance and health in
humans.},
Doi = {10.1093/emph/eow018},
Key = {fds327317}
}
@article{fds281846,
Author = {Krystal, AD},
Title = {New Developments in Insomnia Medications of Relevance to
Mental Health Disorders.},
Journal = {Psychiatr Clin North Am},
Volume = {38},
Number = {4},
Pages = {843-860},
Year = {2015},
Month = {December},
ISSN = {0193-953X},
url = {http://dx.doi.org/10.1016/j.psc.2015.08.001},
Abstract = {Many insomnia medications with high specificity have become
available recently. They provide a window into the clinical
effects of modulating specific brain systems and establish a
new guiding principal for conceptualizing insomnia
medications: "mechanism matters." A new paradigm for
insomnia therapy in which specific drugs are selected to
target the specific type of sleep difficulty for each
patient includes administering specific treatments for
patients with insomnia comorbid with particular psychiatric
disorders. This article reviews insomnia medications and
discusses the implications for optimizing the treatment of
insomnia occurring comorbid with psychiatric
conditions.},
Doi = {10.1016/j.psc.2015.08.001},
Key = {fds281846}
}
@article{fds319929,
Author = {Morin, CM and Drake, CL and Harvey, AG and Krystal, AD and Manber, R and Riemann, D and Spiegelhalder, K},
Title = {Insomnia disorder.},
Journal = {Nature Reviews. Disease Primers},
Volume = {1},
Pages = {15026},
Year = {2015},
Month = {September},
url = {http://dx.doi.org/10.1038/nrdp.2015.26},
Abstract = {Insomnia disorder affects a large proportion of the
population on a situational, recurrent or chronic basis and
is among the most common complaints in medical practice. The
disorder is predominantly characterized by dissatisfaction
with sleep duration or quality and difficulties initiating
or maintaining sleep, along with substantial distress and
impairments of daytime functioning. It can present as the
chief complaint or, more often, co-occurs with other medical
or psychiatric disorders, such as pain and depression.
Persistent insomnia has been linked with adverse long-term
health outcomes, including diminished quality of life and
physical and psychological morbidity. Despite its high
prevalence and burden, the aetiology and pathophysiology of
insomnia is poorly understood. In the past decade, important
changes in classification and diagnostic paradigms have
instigated a move from a purely symptom-based
conceptualization to the recognition of insomnia as a
disorder in its own right. These changes have been
paralleled by key advances in therapy, with generic
pharmacological and psychological interventions being
increasingly replaced by approaches that have sleep-specific
and insomnia-specific therapeutic targets. Psychological and
pharmacological therapies effectively reduce the time it
takes to fall asleep and the time spent awake after sleep
onset, and produce a modest increase in total sleep time;
these are outcomes that correlate with improvements in
daytime functioning. Despite this progress, several
challenges remain, including the need to improve our
knowledge of the mechanisms that underlie insomnia and to
develop more cost-effective, efficient and accessible
therapies.},
Doi = {10.1038/nrdp.2015.26},
Key = {fds319929}
}
@article{fds281848,
Author = {Peterchev, AV and Krystal, AD and Rosa, MA and Lisanby,
SH},
Title = {Individualized Low-Amplitude Seizure Therapy: Minimizing
Current for Electroconvulsive Therapy and Magnetic Seizure
Therapy.},
Journal = {Neuropsychopharmacology},
Volume = {40},
Number = {9},
Pages = {2076-2084},
Year = {2015},
Month = {August},
ISSN = {0893-133X},
url = {http://dx.doi.org/10.1038/npp.2015.122},
Abstract = {Electroconvulsive therapy (ECT) at conventional current
amplitudes (800-900 mA) is highly effective but carries the
risk of cognitive side effects. Lowering and individualizing
the current amplitude may reduce side effects by virtue of a
less intense and more focal electric field exposure in the
brain, but this aspect of ECT dosing is largely unexplored.
Magnetic seizure therapy (MST) induces a weaker and more
focal electric field than ECT; however, the pulse amplitude
is not individualized and the minimum amplitude required to
induce a seizure is unknown. We titrated the amplitude of
long stimulus trains (500 pulses) as a means of determining
the minimum current amplitude required to induce a seizure
with ECT (bilateral, right unilateral, bifrontal, and
frontomedial electrode placements) and MST (round coil on
vertex) in nonhuman primates. Furthermore, we investigated a
novel method of predicting this amplitude-titrated seizure
threshold (ST) by a non-convulsive measurement of motor
threshold (MT) using single pulses delivered through the ECT
electrodes or MST coil. Average STs were substantially lower
than conventional pulse amplitudes (112-174 mA for ECT and
37.4% of maximum device amplitude for MST). ST was more
variable in ECT than in MST. MT explained 63% of the ST
variance and is hence the strongest known predictor of ST.
These results indicate that seizures can be induced with
less intense electric fields than conventional ECT that may
be safer; efficacy and side effects should be evaluated in
clinical studies. MT measurement could be a faster and safer
alternative to empirical ST titration for ECT and
MST.},
Doi = {10.1038/npp.2015.122},
Key = {fds281848}
}
@article{fds311655,
Author = {Krystal, AD},
Title = {Current, emerging, and newly available insomnia
medications.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {76},
Number = {8},
Pages = {e1045},
Year = {2015},
Month = {August},
ISSN = {0160-6689},
url = {http://dx.doi.org/10.4088/JCP.14046tx2c},
Abstract = {Research into the sleep-wake cycle has provided new
treatment targets for patients with insomnia as well as a
better understanding of how medications affect sleep
processes. Current insomnia medications, including
benzodiazepines and nonbenzodiazepines, focus on enhancing
sleep-promoting systems through broad antagonism of GABA.
Other medications that promote sleep by blocking
wake-promoting systems include antidepressants,
antipsychotics, and antihistamines, but adverse effects and
nonspecific therapeutic effects limit their use. New and
emerging insomnia medications are focusing on blocking
wake-promoting systems via more selective antagonism of
orexin, serotonin, and norepinephrine. These medications may
offer improved efficacy with fewer adverse
effects.},
Doi = {10.4088/JCP.14046tx2c},
Key = {fds311655}
}
@article{fds281845,
Author = {Ivgy-May, N and Ruwe, F and Krystal, A and Roth, T},
Title = {Esmirtazapine in non-elderly adult patients with primary
insomnia: efficacy and safety from a randomized, 6-week
sleep laboratory trial.},
Journal = {Sleep Med},
Volume = {16},
Number = {7},
Pages = {838-844},
Year = {2015},
Month = {July},
ISSN = {1389-9457},
url = {http://dx.doi.org/10.1016/j.sleep.2015.04.001},
Abstract = {OBJECTIVE: Esmirtazapine (Org 50081), a medication that
binds with high affinity to serotonin 5-HT2A and histamine-1
receptors, was evaluated as a potential treatment for
insomnia. METHODS: Adults with primary insomnia were treated
with esmirtazapine (3.0 or 4.5 mg) or placebo in this
6-week, double-blind, randomized, polysomnography (PSG)
study. The end points included wake time after sleep onset
(WASO) (primary), latency to persistent sleep, and total
sleep time. Patient-reported parameters were also evaluated,
including sleep quality and satisfaction with sleep
duration. Residual daytime effects and rebound insomnia
(sleep parameters during the single-blind placebo run-out
week after treatment ended) were also assessed. RESULTS:
Overall, 419 patients were randomized and 366 (87%)
completed treatment. The median decrease in PSG WASO
(double-blind average) was 20.5 min for placebo, and
52.0 min and 53.6 min for the 3.0- and 4.5-mg
esmirtazapine groups, respectively (P < 0.0001 vs.
placebo for both doses). Changes in the other PSG parameters
and in all patient-reported parameters were also
statistically significant with both doses versus placebo.
Overall, 35-42% of esmirtazapine-treated patients had
adverse events (AEs) versus 29% in the placebo group. AEs
were mild or moderate in most esmirtazapine-treated
patients. Furthermore, the incidence of AEs leading to
discontinuation was low (<8%). CONCLUSIONS: Six weeks of
treatment with esmirtazapine was associated with consistent
improvements in objective and patient-reported parameters of
sleep onset, maintenance, and duration. It was generally
well tolerated, and residual daytime effects were minimal
and no rebound insomnia was observed.},
Doi = {10.1016/j.sleep.2015.04.001},
Key = {fds281845}
}
@article{fds281849,
Author = {Krystal, JH and Stossel, S and Krystal, AD},
Title = {Restricting Benzodiazepines to Short-Term
Prescription.},
Journal = {Jama Psychiatry},
Volume = {72},
Number = {7},
Pages = {734-735},
Year = {2015},
Month = {July},
ISSN = {2168-622X},
url = {http://dx.doi.org/10.1001/jamapsychiatry.2015.0351},
Doi = {10.1001/jamapsychiatry.2015.0351},
Key = {fds281849}
}
@article{fds281852,
Author = {McCall, WV and Benca, RM and Rosenquist, PB and Riley, MA and Hodges, C and Gubosh, B and McCloud, L and Newman, JC and Case, D and Rumble, M and Mayo,
M and White, KH and Phillips, M and Krystal, AD},
Title = {A multi-site randomized clinical trial to reduce suicidal
ideation in suicidal adult outpatients with Major Depressive
Disorder: Development of a methodology to enhance
safety.},
Journal = {Clin Trials},
Volume = {12},
Number = {3},
Pages = {189-198},
Year = {2015},
Month = {June},
ISSN = {1740-7745},
url = {http://dx.doi.org/10.1177/1740774515573958},
Abstract = {BACKGROUND/AIMS: Suicide is a major public health concern,
yet there are very few randomized clinical trials that have
been conducted to reduce suicidal ideation in patients at
risk of suicide. We describe the rationale and refinements
of such a trial that is designed to assess the effect of a
hypnotic medication on suicidal ideation in adult
outpatients currently experiencing suicidal ideation.
METHODS: "Reducing Suicidal Ideation Through Insomnia
Treatment" is a multi-site randomized clinical trial that
includes three recruiting sites and one data management
site. This 4-year study is in its second year of
recruitment. The purpose of the study is to compare hypnotic
medication versus placebo as an add-on treatment to a
selective serotonin reuptake inhibitor as a means of
reducing suicidal ideation in depressed adult outpatients
with insomnia and suicidal ideation. The safety features of
the study follow the 2001 National Institutes of Health
guidelines for studies that include patients at risk of
suicide. RESULTS: In total, 584 potential participants have
undergone telephone screening; 67% of these failed the phone
screen, most often due to an absence of expressed suicidal
ideation (26% of the telephone screen fails). A total of 115
people appeared for a face-to-face baseline assessment, and
40 of these had completed a taper off of their ineffective
psychotropic medications before the baseline assessments. In
all, 64% of those who completed baseline assessments failed
to proceed to randomization, most commonly because of no
clinically significant suicidal ideation (51% of those
excluded at baseline). One participant was offered and
accepted voluntary psychiatric hospitalization in lieu of
study participation. Thus far, 40 participants have been
randomized into the study and 88.7% of scheduled visits have
been attended, with 93.8% adherence to the selective
serotonin reuptake inhibitor and 91.6% adherence to the
randomized hypnotic versus placebo. None of the randomized
participants have required hospitalization or had a suicide
attempt. CONCLUSION: By carefully considering the inclusion
and exclusion criteria and other safety features, the safe
conduct of randomized clinical trials in suicidal adult
patients is possible, including the inclusion of
participants who have undergone a prescribed tapering off of
psychotropic medications prior to baseline
assessment.},
Doi = {10.1177/1740774515573958},
Key = {fds281852}
}
@article{fds322854,
Author = {Szabo, ST and Kinon, BJ and Brannan, SK and Krystal, AK and van Gerven,
JMA and Mahableshwarkar, A and Sachs, GS},
Title = {Lessons learned and potentials for improvement in cns drug
development: Isctm section on designing the right series of
experiments},
Journal = {Innovations in Clinical Neuroscience},
Volume = {12},
Number = {3-4},
Pages = {11S-25S},
Year = {2015},
Month = {March},
Abstract = {Once a molecule has been characterized as engaging an
identified target at the appropriate location (affinity and
potency), the next step involves designing experiments that
will determine its pharmacodynamic activities both for
efficacy (on target) and safety-tolerability (on/off
target). Two expert presentations focused on looking back at
completed programs and two concentrated on looking forward
at ongoing programs. Specific discussions pertain to
assessment of pharmacologic agonists (mGluR2/3, kopiate,
peroxisome proliferatoractivated receptor gamma) and
antagonists (orexin and cannabinoid) in disorders of
cognition, mood, and anxiety. Advanced experimental study
designs using genetics to guide a treatment trial in
Alzheimer’s disease and neural target-based approaches as
the primary outcome measure in the National Institute of
Mental Healthsponsored Fast-Fail Trials (FAST)- Mood and
Anxiety Spectrum Disorders (MAS) initiative for depression
showcases novel methodological approaches. Of interest, some
of these initiatives were successful, while others were not,
and two are currently ongoing. In conclusion, methodologies
that were utilized and are currently employed to reach a
successful clinical drug trial outcome are appreciated, and
in case of failure, approaches to reviewing programs to
enable learning that would be helpful to future programs are
brought forth. This article is based on proceedings from the
“Designing the Right Series of Experiments” session,
which was held during the International Society for Clinical
Trials Meeting (ISCTM) in Philadelphia, Pennsylvania,
September 30 to October 2, 2013.},
Key = {fds322854}
}
@article{fds281844,
Author = {Rapp, PE and Keyser, DO and Albano, A and Hernandez, R and Gibson, DB and Zambon, RA and David Hairston and W and Hughes, JD and Krystal, A and Nichols, AS},
Title = {Traumatic brain injury detection using electrophysiological
methods},
Journal = {Frontiers in Human Neuroscience},
Volume = {9},
Number = {FEB},
Publisher = {FRONTIERS MEDIA SA},
Year = {2015},
Month = {February},
url = {http://dx.doi.org/10.3389/fnhum.2015.00011},
Abstract = {Measuring neuronal activity with electrophysiological
methods may be useful in detecting neurological
dysfunctions, such as mild traumatic brain injury
(mTBI).This approach may be particularly valuable for rapid
detection in at-risk populations including military service
members and athletes. Electrophysiological methods, such as
quantitative electroencephalography (qEEG) and recording
event-related potentials (ERPs) may be promising; however,
the field is nascent and significant controversy exists on
the efficacy and accuracy of the approaches as diagnostic
tools. For example, the specific measures derived from an
electroencephalogram (EEG) that are most suitable as markers
of dysfunction have not been clearly established. A study
was conducted to summarize and evaluate the statistical
rigor of evidence on the overall utility of qEEG as an mTBI
detection tool. The analysis evaluated qEEG
measures/parameters that may be most suitable as fieldable
diagnostic tools, identified other types of EEG measures and
analysis methods of promise, recommended specific measures
and analysis methods for further development as mTBI
detection tools, identified research gaps in the field, and
recommended future research and development thrust areas.
The qEEG study group formed the following conclusions: (1)
Individual qEEG measures provide limited diagnostic utility
for mTBI. However, many measures can be important features
of qEEG discriminant functions, which do show significant
promise as mTBI detection tools. (2) ERPs offer utility in
mTBI detection. In fact, evidence indicates that ERPs can
identify abnormalities in cases where EEGs alone are
non-disclosing. (3)The standard mathematical procedures used
in the characterization of mTBI EEGs should be expanded to
incorporate newer methods of analysis including non-linear
dynamical analysis, complexity measures, analysis of causal
interactions, graph theory, and information dynamics. (4)
Reports of high specificity in qEEG evaluations of TBI must
be interpreted with care. High specificities have been
reported in carefully constructed clinical studies in which
healthy controls were compared against a carefully selected
TBI population. The published literature indicates, however,
that similar abnormalities in qEEG measures are observed in
other neuropsychiatric disorders. While it may be possible
to distinguish a clinical patient from a healthy control
participant with this technology, these measures are
unlikely to discriminate between, for example, major
depressive disorder, bipolar disorder, or TBI. The
specificities observed in these clinical studies may well be
lost in real world clinical practice. (5)The absence of
specificity does not preclude clinical utility. The
possibility of use as a longitudinal measure of treatment
response remains. However, efficacy as a longitudinal
clinical measure does require acceptable test-retest
reliability. To date, very few test-retest reliability
studies have been published with qEEG data obtained from TBI
patients or from healthy controls. This is a particular
concern because high variability is a known characteristic
of the injured central nervous system.},
Doi = {10.3389/fnhum.2015.00011},
Key = {fds281844}
}
@article{fds281847,
Author = {Leuchter, AF and Cook, IA and Feifel, D and Goethe, JW and Husain, M and Carpenter, LL and Thase, ME and Krystal, AD and Philip, NS and Bhati,
MT and Burke, WJ and Howland, RH and Sheline, YI and Aaronson, ST and Iosifescu, DV and O'Reardon, JP and Gilmer, WS and Jain, R and Burgoyne,
KS and Phillips, B and Manberg, PJ and Massaro, J and Hunter, AM and Lisanby, SH and George, MS},
Title = {Efficacy and Safety of Low-field Synchronized Transcranial
Magnetic Stimulation (sTMS) for Treatment of Major
Depression.},
Journal = {Brain Stimul},
Volume = {8},
Number = {4},
Pages = {787-794},
Year = {2015},
ISSN = {1935-861X},
url = {http://dx.doi.org/10.1016/j.brs.2015.05.005},
Abstract = {BACKGROUND: Transcranial Magnetic Stimulation (TMS)
customarily uses high-field electromagnets to achieve
therapeutic efficacy in Major Depressive Disorder (MDD).
Low-field magnetic stimulation also may be useful for
treatment of MDD, with fewer treatment-emergent adverse
events. OBJECTIVE/HYPOTHESIS: To examine efficacy, safety,
and tolerability of low-field magnetic stimulation
synchronized to an individual's alpha frequency (IAF)
(synchronized TMS, or sTMS) for treatment of MDD. METHODS:
Six-week double-blind sham-controlled treatment trial of a
novel device that used three rotating neodymium magnets to
deliver sTMS treatment. IAF was determined from a
single-channel EEG prior to first treatment. Subjects had
baseline 17-item Hamilton Depression Rating Scale
(HamD17) ≥ 17. RESULTS: 202 subjects comprised the
intent-to-treat (ITT) sample, and 120 subjects completed
treatment per-protocol (PP). There was no difference in
efficacy between active and sham in the ITT sample. Subjects
in the PP sample (N = 59), however, had significantly
greater mean decrease in HamD17 than sham (N = 60) (-9.00
vs. -6.56, P = 0.033). PP subjects with a history of poor
response or intolerance to medication showed greater
improvement with sTMS than did treatment-naïve subjects
(-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample
reflects exclusion of subjects who received fewer than 80%
of scheduled treatments or were inadvertently treated at the
incorrect IAF; these subgroups failed to separate from sham.
There was no difference in adverse events between sTMS and
sham, and no serious adverse events attributable to sTMS.
CONCLUSIONS: Results suggest that sTMS may be effective,
safe, and well tolerated for treating MDD when administered
as intended.},
Doi = {10.1016/j.brs.2015.05.005},
Key = {fds281847}
}
@article{fds281854,
Author = {Tek, C and Palmese, LB and Krystal, AD and Srihari, VH and DeGeorge, PC and Reutenauer, EL and Guloksuz, S},
Title = {The impact of eszopiclone on sleep and cognition in patients
with schizophrenia and insomnia: a double-blind, randomized,
placebo-controlled trial.},
Journal = {Schizophrenia Research},
Volume = {160},
Number = {1-3},
Pages = {180-185},
Year = {2014},
Month = {December},
ISSN = {0920-9964},
url = {http://dx.doi.org/10.1016/j.schres.2014.10.002},
Abstract = {BACKGROUND: Insomnia is frequent in schizophrenia and may
contribute to cognitive impairment as well as overuse of
weight inducing sedative antipsychotics. We investigated the
effects of eszopiclone on sleep and cognition for patients
with schizophrenia-related insomnia in a double-blind
placebo controlled study, followed by a two-week,
single-blind placebo phase. METHODS: Thirty-nine clinically
stable outpatients with schizophrenia or schizoaffective
disorder and insomnia were randomized to either 3mg
eszopiclone (n=20) or placebo (n=19). Primary outcome
measure was change in Insomnia Severity Index (ISI) over 8
weeks. Secondary outcome measure was change in MATRICS
Consensus Cognitive Battery (MATRICS). Sleep diaries,
psychiatric symptoms, and quality of life were also
monitored. RESULTS: ISI significantly improved more in
eszopiclone (mean=-10.7, 95% CI=-13.2; -8.2) than in placebo
(mean=-6.9, 95% CI=-9.5; -4.3) with a between-group
difference of -3.8 (95% CI=-7.5; -0.2). MATRICS score change
did not differ between groups. On further analysis there was
a significant improvement in the working memory test,
letter-number span component of MATRICS (mean=9.8±9.2,
z=-2.00, p=0.045) only for subjects with schizophrenia on
eszopiclone. There were improvements in sleep diary items in
both groups with no between-group differences. Psychiatric
symptoms remained stable. Discontinuation rates were
similar. Sleep remained improved during single-blind placebo
phase after eszopiclone was stopped, but the working memory
improvement in patients with schizophrenia was not durable.
CONCLUSIONS: Eszopiclone stands as a safe and effective
alternative for the treatment of insomnia in patients with
schizophrenia. Its effects on cognition require further
study.},
Doi = {10.1016/j.schres.2014.10.002},
Key = {fds281854}
}
@article{fds281856,
Author = {Calabrese, JR and Fava, M and Garibaldi, G and Grunze, H and Krystal,
AD and Laughren, T and Macfadden, W and Marin, R and Nierenberg, AA and Tohen, M},
Title = {Methodological approaches and magnitude of the clinical
unmet need associated with amotivation in mood
disorders.},
Journal = {J Affect Disord},
Volume = {168},
Pages = {439-451},
Year = {2014},
Month = {October},
ISSN = {0165-0327},
url = {http://dx.doi.org/10.1016/j.jad.2014.06.056},
Abstract = {BACKGROUND: There is growing research interest in studying
motivational deficits in different neuropsychiatric
disorders because these symptoms appear to be more common
than originally reported and negatively impact long-term
functional outcomes. However, there is considerable
ambiguity in the terminology used to describe motivational
deficits in the scientific literature. For the purposes of
this manuscript, the term "amotivation" will be utilised in
the context of mood disorders, since this is considered a
more inclusive/appropriate term for this patient population.
Other challenges impacting the study of amotivation in mood
disorders, include: appropriate patient population
selection; managing or controlling for potential confounding
factors; the lack of gold-standard diagnostic criteria and
assessment scales; and determination of the most appropriate
study duration. METHODS: This paper summarises the search
for a consensus by a group of experts in the optimal
approach to studying amotivation in mood disorders. RESULTS:
The consensus of this group is that amotivation in mood
disorders is a legitimate therapeutic target, given the
magnitude of the associated unmet needs, and that
proof-of-concept studies should be conducted in order to
facilitate subsequent larger investigations. The focus of
this manuscript is to consider the study of amotivation, as
a residual symptom of major depressive disorder (MDD) or
bipolar depression (BD), following adequate treatment with a
typical antidepressant or mood stabiliser/antipsychotic,
respectively. DISCUSSION: There is a paucity of data
studying amotivation in mood disorders. This manuscript
provides general guidance on the most appropriate study
design(s) and methodology to assess potential therapeutic
options for the management of residual amotivation in mood
disorders.},
Doi = {10.1016/j.jad.2014.06.056},
Key = {fds281856}
}
@article{fds281857,
Author = {Goforth, HW and Preud'homme, XA and Krystal, AD},
Title = {A randomized, double-blind, placebo-controlled trial of
eszopiclone for the treatment of insomnia in patients with
chronic low back pain.},
Journal = {Sleep},
Volume = {37},
Number = {6},
Pages = {1053-1060},
Year = {2014},
Month = {June},
ISSN = {0161-8105},
url = {http://dx.doi.org/10.5665/sleep.3760},
Abstract = {STUDY OBJECTIVES: Insomnia, which is very common in patients
with chronic low back pain (LBP), has long been viewed as a
pain symptom that did not merit specific treatment. Recent
data suggest that adding insomnia therapy to pain-targeted
treatment should improve outcome; however, this has not been
empirically tested in LBP or in any pain condition treated
with a standardized pain medication regimen. We sought to
test the hypothesis that adding insomnia therapy to
pain-targeted treatment might improve sleep and pain in LBP.
DESIGN: Double-blind, placebo-controlled, parallel-group,
1-mo trial. SETTING: Duke University Medical Center
Outpatient Sleep Clinic. PATIENTS: Fifty-two adult
volunteers with LBP of at least 3 mo duration who met
diagnostic criteria for insomnia (mean age: 42.5 y; 63%
females). INTERVENTIONS: Subjects were randomized to
eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching
placebo plus naproxen 500 mg twice a day. MEASUREMENTS AND
RESULTS: ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN
INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and
nearly all sleep measures as well as visual analog scale
pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary
pain outcome), and depression (mean Hamilton Depression
Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared
with placebo. Changes in pain ratings were significantly
correlated with changes in sleep. CONCLUSIONS: The addition
of insomnia-specific therapy to a standardized naproxen pain
regimen significantly improves sleep, pain, and depression
in patients with chronic low back pain (LBP). The findings
indicate the importance of administering both sleep and
pain-directed therapies to patients with LBP in clinical
practice and provide strong evidence that improving sleep
disturbance may improve pain. TRIAL REGISTRATION:
clinicaltrials.gov identifier: NCT00365976.},
Doi = {10.5665/sleep.3760},
Key = {fds281857}
}
@article{fds281858,
Author = {McClintock, SM and Choi, J and Deng, Z-D and Appelbaum, LG and Krystal,
AD and Lisanby, SH},
Title = {Multifactorial determinants of the neurocognitive effects of
electroconvulsive therapy.},
Journal = {J Ect},
Volume = {30},
Number = {2},
Pages = {165-176},
Year = {2014},
Month = {June},
ISSN = {1095-0680},
url = {http://hdl.handle.net/10161/10644 Duke open
access},
Abstract = {For many patients with neuropsychiatric illnesses, standard
psychiatric treatments with mono or combination
pharmacotherapy, psychotherapy, and transcranial magnetic
stimulation are ineffective. For these patients with
treatment-resistant neuropsychiatric illnesses, a main
therapeutic option is electroconvulsive therapy (ECT).
Decades of research have found ECT to be highly effective;
however, it can also result in adverse neurocognitive
effects. Specifically, ECT results in disorientation after
each session, anterograde amnesia for recently learned
information, and retrograde amnesia for previously learned
information. Unfortunately, the neurocognitive effects and
underlying mechanisms of action of ECT remain poorly
understood. The purpose of this paper was to synthesize the
multiple moderating and mediating factors that are thought
to underlie the neurocognitive effects of ECT into a
coherent model. Such factors include demographic and
neuropsychological characteristics, neuropsychiatric
symptoms, ECT technical parameters, and ECT-associated
neurophysiological changes. Future research is warranted to
evaluate and test this model, so that these findings may
support the development of more refined clinical seizure
therapy delivery approaches and efficacious cognitive
remediation strategies to improve the use of this important
and widely used intervention tool for neuropsychiatric
diseases.},
Doi = {10.1097/YCT.0000000000000137},
Key = {fds281858}
}
@article{fds281863,
Author = {Michelson, D and Snyder, E and Paradis, E and Chengan-Liu, M and Snavely, DB and Hutzelmann, J and Walsh, JK and Krystal, AD and Benca,
RM and Cohn, M and Lines, C and Roth, T and Herring,
WJ},
Title = {Safety and efficacy of suvorexant during 1-year treatment of
insomnia with subsequent abrupt treatment discontinuation: a
phase 3 randomised, double-blind, placebo-controlled
trial.},
Journal = {Lancet Neurol},
Volume = {13},
Number = {5},
Pages = {461-471},
Year = {2014},
Month = {May},
ISSN = {1474-4422},
url = {http://dx.doi.org/10.1016/S1474-4422(14)70053-5},
Abstract = {BACKGROUND: Suvorexant (MK-4305) is an orexin receptor
antagonist shown to be efficacious for insomnia over 3
months. We aimed to assess its clinical profile during and
after 1 year of treatment. METHODS: We did a randomised,
placebo-controlled, parallel-group trial at 106
investigational centres in the Americas, Australia, Europe,
and South Africa from December, 2009, to August, 2011.
Patients aged 18 years or older with primary insomnia by
DSM-IV-TR criteria were assigned using a computer-generated
randomised allocation schedule to receive nightly suvorexant
(40 mg for patients younger than 65 years, 30 mg for
patients aged 65 years or older) or placebo at a 2:1 ratio
for 1 year with a subsequent 2-month randomised
discontinuation phase in which patients on suvorexant either
continued suvorexant or were abruptly switched to placebo
while patients on placebo remained on placebo. Treatment
assignment was masked from patients and investigators. The
primary objective was to assess the safety and tolerability
of suvorexant for up to 1 year. Secondary objectives were to
assess the efficacy of suvorexant for improving
patient-reported subjective total sleep time (sTST) and time
to sleep onset (sTSO) over the first month of treatment.
Efficacy endpoints over the first month were assessed with a
mixed model with terms for baseline value of the response
variable, age, sex, region, treatment, time, and treatment
by time interaction. This trial is registered with
ClinicalTrials.gov, number NCT01021813. FINDINGS: 322 (62%)
of 522 patients randomly assigned to receive suvorexant and
162 (63%) of 259 assigned to receive placebo completed the
1-year phase. Over 1 year, 362 (69%) of 521 patients treated
with suvorexant experienced any adverse events compared with
164 (64%) of 258 treated with placebo. Serious adverse
events were recorded in 27 patients (5%) who received
suvorexant and 17 (7%) who received placebo. The most common
adverse event, somnolence, was reported for 69 patients
(13%) who received suvorexant and seven (3%) who received
placebo. At month 1, suvorexant (517 patients in the
efficacy population) showed greater efficacy than placebo
(254 in the efficacy population) in improving sTST (38·7
min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0;
p<0·0001) and sTSO (-18·0 min vs -8·4 min, difference
-9·5, -14·6 to -4·5; p=0·0002). INTERPRETATION: Our
findings show that suvorexant was generally safe and well
tolerated over 1 year of nightly treatment in patients with
insomnia, with efficacy noted for subjective measures of
sleep onset and maintenance. FUNDING: Merck & Co
Inc.},
Doi = {10.1016/S1474-4422(14)70053-5},
Key = {fds281863}
}
@article{fds281867,
Author = {Krystal, AD and Zhang, W and Davidson, JRT and Connor,
KM},
Title = {The sleep effects of tiagabine on the first night of
treatment predict post-traumatic stress disorder response at
three weeks.},
Journal = {J Psychopharmacol},
Volume = {28},
Number = {5},
Pages = {457-465},
Year = {2014},
Month = {May},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24288237},
Abstract = {INTRODUCTION: We sought to test the hypothesis that
improvements in sleep might mediate treatment-related
improvements in daytime symptoms of post-traumatic stress
disorder (PTSD). We evaluated whether changes in sleep
occurring on the first night of tiagabine (a gamma-amino
butyric acid (GABA) reuptake inhibitor) administration
predicted subsequent PTSD response. METHODS: This was an
open-label three-week polysomnographic (PSG) study of
nightly treatment with tiagabine dosing from 2-12 mg
including 20 adults with PTSD with ≥30 min of
self-reported and PSG wake time after sleep onset (WASO).
RESULTS: A treatment night 1 decrease in self-reported and
PSG WASO and an increase in slow-wave sleep (SWS) accounted
for 94% of the variance in week 3 Short PTSD Rating
Interview (SPRINT) score, the primary outcome measure
(p<0.001). Increased night 1 SWS also accounted for 91% of
the variance in Work/School Impairment and 45% of the
variance in Social Life Impairment as measured with the
Sheehan Disability Scale (p<0.001). These relationships were
much stronger correlates of three-week outcome than
three-week sleep effects. CONCLUSIONS: The initial sleep
response to tiagabine may mediate or be an indicator of the
subsequent PTSD response. The findings highlight the
importance of sleep maintenance and SWS in the treatment of
PTSD and also suggest a potential relationship between SWS
and daytime function.},
Doi = {10.1177/0269881113509903},
Key = {fds281867}
}
@article{fds281876,
Author = {Mirrakhimov, AE and Brewbaker, CL and Krystal, AD and Kwatra,
MM},
Title = {Obstructive sleep apnea and delirium: exploring possible
mechanisms.},
Journal = {Sleep Breath},
Volume = {18},
Number = {1},
Pages = {19-29},
Year = {2014},
Month = {March},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23584846},
Abstract = {INTRODUCTION: Obstructive sleep apnea (OSA) is a medical
disorder strongly associated with multiple comorbidities and
postoperative complications. Current evidence suggests that
OSA disturbs fundamental biochemical processes, leading to
low-grade systemic inflammation and oxidative stress. Animal
models have shown that OSA may lead to apoptosis of central
neurons. In clinical studies, oxygen desaturation index and
sleep fragmentation have been shown to be independently
associated with cognitive dysfunction. Moreover, in several
studies, patients with OSA were shown to have decreased
brain activation in multiple brain areas. OSA AND DELIRIUM:
The possibility of an association between OSA and delirium
has been highlighted in several case reports. The first
prospective study of the possible link between apnea and
delirium showed that the presence of OSA was independently
associated with the occurrence of delirium after knee
replacement surgery. CONCLUSIONS: Therefore, we suggest that
OSA should be considered as a risk factor for delirium, and
clinicians should assess patients for OSA and related risk
factors prior to surgery. However, further research is
required to shed light on the mechanisms connecting these
disorders and on whether the treatment of OSA affects the
incidence of delirium.},
Doi = {10.1007/s11325-013-0846-z},
Key = {fds281876}
}
@article{fds281864,
Author = {Greve, DN and Duntley, SP and Larson-Prior, L and Krystal, AD and Diaz,
MT and Drummond, SPA and Thein, SG and Kushida, CA and Yang, R and Thomas,
RJ},
Title = {Effect of armodafinil on cortical activity and working
memory in patients with residual excessive sleepiness
associated with CPAP-Treated OSA: a multicenter fMRI
study.},
Journal = {J Clin Sleep Med},
Volume = {10},
Number = {2},
Pages = {143-153},
Year = {2014},
Month = {February},
ISSN = {1550-9389},
url = {http://dx.doi.org/10.5664/jcsm.3440},
Abstract = {STUDY OBJECTIVE: To assess the effect of armodafinil on
task-related prefrontal cortex activation using functional
magnetic resonance imaging (fMRI) in patients with
obstructive sleep apnea (OSA) and excessive sleepiness
despite continuous positive airway pressure (CPAP) therapy.
METHODS: This 2-week, multicenter, prospective, randomized,
double-blind, placebo-controlled, parallel-group study was
conducted at five neuroimaging sites and four collaborating
clinical study centers in the United States. Patients were
40 right-handed or ambidextrous men and women aged between
18 and 60 years, with OSA and persistent sleepiness, as
determined by multiple sleep latency and Epworth Sleepiness
Scale scores, despite effective, stable use of CPAP.
Treatment was randomized (1:1) to once-daily armodafinil 200
mg or placebo. The primary efficacy outcome was a change
from baseline at week 2 in the volume of activation meeting
the predefined threshold in the dorsolateral prefrontal
cortex during a 2-back working memory task. The key
secondary measure was the change in task response latency.
RESULTS: No significant differences were observed between
treatment groups in the primary or key secondary outcomes.
Armodafinil was generally well tolerated. The most common
adverse events (occurring in more than one patient [5%])
were headache (19%), nasopharyngitis (14%), and diarrhea
(10%). CONCLUSIONS: Armodafinil did not improve
fMRI-measured functional brain activation in CPAP-treated
patients with OSA and excessive sleepiness. STUDY
REGISTRATION: Double-Blind, Placebo-Controlled, Functional
Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal
Cortical Activation in Patients With Residual Excessive
Sleepiness Associated With Obstructive Sleep
Apnea/Hypopnea.},
Doi = {10.5664/jcsm.3440},
Key = {fds281864}
}
@article{fds281877,
Author = {Wang, X and Bey, AL and Chung, L and Krystal, AD and Jiang,
Y-H},
Title = {Therapeutic approaches for shankopathies.},
Journal = {Dev Neurobiol},
Volume = {74},
Number = {2},
Pages = {123-135},
Year = {2014},
Month = {February},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23536326},
Abstract = {Despite recent advances in understanding the molecular
mechanisms of autism spectrum disorders (ASD), the current
treatments for these disorders are mostly focused on
behavioral and educational approaches. The considerable
clinical and molecular heterogeneity of ASD present a
significant challenge to the development of an effective
treatment targeting underlying molecular defects. Deficiency
of SHANK family genes causing ASD represent an exciting
opportunity for developing molecular therapies because of
strong genetic evidence for SHANK as causative genes in ASD
and the availability of a panel of Shank mutant mouse
models. In this article, we review the literature suggesting
the potential for developing therapies based on molecular
characteristics and discuss several exciting themes that are
emerging from studying Shank mutant mice at the molecular
level and in terms of synaptic function.},
Doi = {10.1002/dneu.22084},
Key = {fds281877}
}
@article{fds281859,
Author = {Low, Y and Goforth, H and Preud'homme, X and Edinger, J and Krystal,
A},
Title = {Insomnia in HIV-infected patients: pathophysiologic
implications.},
Journal = {Aids Rev},
Volume = {16},
Number = {1},
Pages = {3-13},
Year = {2014},
ISSN = {1139-6121},
Abstract = {The prevalence of insomnia in the HIV-seropositive
population is estimated to be 29-97%, far greater than the
10% general population prevalence. We carried out a
systematic review to assess whether the prevalence of
insomnia is indeed higher in HIV-seropositive patients and
to better understand the correlates of insomnia in order to
attempt to explain the dramatically higher prevalence.
Nineteen studies met our search criteria and were included
in this review. We found that prior studies estimated the
rate of disturbed sleep, but not a single study estimated
the prevalence of insomnia using insomnia diagnostic
criteria, which require that sleep disturbance occur
frequently, persistently, and in association with impairment
in quality of life or daytime function. We also found that
in addition to correlates of sleep disturbance seen in the
general population, there are also correlates specific to
the HIV-seropositive population: stage and duration of HIV
infection, and cognitive impairment. The most important
conclusion of this review is that the prevalence of insomnia
which meets diagnostic criteria has yet to be estimated in
populations of HIV-seropositive patients and studies are
needed to estimate this prevalence rate. The rate of sleep
disturbance identified in HIV-infected patients (29-97%)
should not be compared against the approximately 10%
prevalence of clinically significant insomnia in the general
population, which would suggest that HIV infection is
associated with an alarming increase in sleep problems.
Instead, this rate is best compared with the rate of sleep
disturbance in the general population, which is roughly
33%.},
Key = {fds281859}
}
@article{fds281871,
Author = {Minkel, J and Krystal, AD},
Title = {Optimizing the Pharmacologic Treatment of Insomnia: Current
Status and Future Horizons.},
Journal = {Sleep Med Clin},
Volume = {8},
Number = {3},
Pages = {333-350},
Year = {2013},
Month = {September},
ISSN = {1556-407X},
url = {http://dx.doi.org/10.1016/j.jsmc.2013.06.002},
Abstract = {A number of medications are available for treating patients
with insomnia. These medications include agents approved as
insomnia therapies by the U.S. Food and Drug Administration
(FDA), agents approved by the FDA for another condition that
are used "off-label" to treat insomnia, and agents available
"over-the-counter" that are taken by individuals with
insomnia. These agents differ in their properties, their
safety and efficacy when used for different insomnia patient
subtypes, and the available data on their efficacy and
safety in these subtypes. As a result, optimizing the
medication treatment of insomnia for a given patient
requires that the clinician select an agent for use which
has characteristics that make it most likely to effectively
and safely address the type of sleep difficulty experienced
by that individual. This article is intended to assist
clinicians and researchers in carrying out this
optimization. It begins by reviewing the basic
characteristics of the medications used to treat insomnia.
This is followed by a review of the fundamental ways that
individuals with insomnia may differ and affect the choice
of medication therapy. This review includes discussions that
illustrate how to best choose a medication based on the
characteristics of the available medications, the key
differences among insomnia patients, and the available
research literature. Lastly, we discuss future directions
for the optimizing pharmacologic management of insomnia. It
is hoped that the treatment tailoring methods discussed
herein serve as a means of improving the clinical management
of insomnia and, thus, improve the lives of the many
patients who suffer from this common and impairing
condition.},
Doi = {10.1016/j.jsmc.2013.06.002},
Key = {fds281871}
}
@article{fds281872,
Author = {Edinger, JD and Means, MK and Krystal, AD},
Title = {Does physiological hyperarousal enhance error rates among
insomnia sufferers?},
Journal = {Sleep},
Volume = {36},
Number = {8},
Pages = {1179-1186},
Year = {2013},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23904678},
Abstract = {OBJECTIVE: To examine the association between physiological
hyperarousal and response accuracy on reaction time tasks
among individuals with insomnia. DESIGN AND SETTING: This
study was conducted at affiliated Veterans Administration
(VA) and academic medical centers using a matched-group,
cross-sectional research design. PARTICIPANTS: Eighty-nine
individuals (48 women) with primary insomnia, PI (MAge =
49.8 ± 17.2 y) and 95 individuals (48 women) who were
well-screened normal sleepers, NS (MAge = 46.9 ± 17.0 y).
METHODS AND MEASURES: Participants underwent 3 nights of
polysomnography followed by daytime testing with a
four-trial Multiple Sleep Latency Test (MSLT). Before each
MSLT nap, they rated their sleepiness and completed
computer-administered reaction time tasks. The mean number
of correct and error responses made by each participant
across testing trials served as dependent measures. The PI
and NS groups were each subdivided into alert (e.g., MSLT
mean onset latency > 8 min) and sleepy (e.g., MSLT mean
onset latency ≤ 8 min) subgroups to allow for testing the
main and interaction effects of participant type and level
of alertness. RESULTS: Alert participants had longer MSLT
latencies than sleepy participants (12.7 versus 5.4 min),
yet both alert and sleepy individuals with PI reported
greater sleepiness than NS. Alert participants also showed
lower sleep efficiencies (83.5% versus 86.2%, P = 0.03),
suggesting 24-h physiological hyperarousal particularly in
the PI group. Individuals with PI had fewer correct
responses on performance testing than did NS, whereas a
significant group × alertness interaction (P = 0.0013)
showed greater error rates among alert individuals with PI
(mean = 4.5 ± 3.6 errors per trial) than among alert NS
(mean = 2.6 ± 1.9 errors per trial). CONCLUSIONS:
Physiological hyperarousal in insomnia may lead to more
apparent daytime alertness yet dispose individuals with
insomnia to higher error rates on tasks requiring their
attention.},
Doi = {10.5665/sleep.2882},
Key = {fds281872}
}
@article{fds281880,
Author = {Krystal, AD and Richelson, E and Roth, T},
Title = {Review of the histamine system and the clinical effects of
H1 antagonists: basis for a new model for understanding the
effects of insomnia medications.},
Journal = {Sleep Med Rev},
Volume = {17},
Number = {4},
Pages = {263-272},
Year = {2013},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23357028},
Abstract = {The pharmacologic management of insomnia has long been
dominated by agents that facilitate gamma amino butyric acid
inhibition. These agents have served as the clinical model
for understanding the pharmacodynamic effects of insomnia
agents according to which sleep effects parallel plasma drug
levels (pharmacokinetic effects). Agents with other
mechanisms also exist for treating insomnia; however, their
effects are less well understood. Many of these diminish the
activity in one or more of the key wake-promoting systems.
This review focuses on one such mechanism, blockade of the
wake promoting effects of histamine via H1 receptor
antagonism. Although drugs with H1 antagonist effects have
long been available, this review was prompted by new studies
of a selective H1 antagonist, which provide the first
indication of the effects that are specifically associated
with H1 antagonism. The findings do not conform to our
long-standing model of insomnia agents in that factors other
than drug blood level are needed to explain the clinical
effects. We suggest a model for understanding these unique
effects based on a review of the basic neurobiology of the
histamine system. In addition to drug blood level, clinical
effects reflect circadian variation in activity in the
histamine system and other parallel wake promoting systems
as well as factors such as pain and stress. We hypothesize
that significant sleep enhancing effects are likely when the
histamine system is relatively active and the activity in
other parallel wake promoting systems is relatively minimal.
Although the focus of this review is on the novel properties
of H1 antagonism, the principles that emerge from this
analysis are most likely relevant to all agents that
selectively block wake promoting systems, and as such, this
review provides a new paradigm for understanding the effects
of insomnia medications.},
Doi = {10.1016/j.smrv.2012.08.001},
Key = {fds281880}
}
@article{fds281881,
Author = {Preud'homme, XA and Amundsen, CL and Webster, GD and Krystal,
AD},
Title = {Comparison of diary-derived bladder and sleep measurements
across OAB individuals, primary insomniacs, and healthy
controls.},
Journal = {Int Urogynecol J},
Volume = {24},
Number = {3},
Pages = {501-508},
Year = {2013},
Month = {March},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22855113},
Abstract = {INTRODUCTION AND HYPOTHESIS: Can diary-derived bladder and
sleep measurements differentiate individuals with overactive
bladder syndrome (OAB) from individuals with primary
insomnia and healthy controls? METHODS: Bladder- and
sleep-diary data were compared in nine OAB, ten insomnia,
and five control individuals. One-way analysis of variance
(ANOVA) was used for normally and Kruskal-Wallis test for
nonnormally distributed variables, followed, when
significant effects were found, by pairwise comparisons.
RESULTS: OAB individuals woke up as frequently as
insomniacs, but their awakenings were respectively shorter
in duration (18.6 vs. 38.1 min.) and were predominantly
initiated by nocturic events (89.2 vs. 23.9 % respectively).
Regardless, their reported quality of sleep was as impaired
as for the insomniacs. Furthermore, smaller mean volume
voided awakenings were evident not only in those with OAB
but also in insomniacs compared to controls. CONCLUSIONS:
Bladder- and sleep-diary data provide means to differentiate
those with OAB from those with insomnia and healthy
controls. Awakenings in OAB individuals were shorter than
those with insomnia and much more likely due to the need to
void. Thus, a reduction in the number of nocturic voids
could be the most appropriate sleep-related outcome for
nocturia therapy in individuals with OAB. In addition,
limited nocturnal bladder capacity, though expected in OAB,
was unexpectedly found in insomnia, possibly reflecting the
role of consciousness (wakefulness at night) in modulating
bladder sensation.},
Doi = {10.1007/s00192-012-1890-0},
Key = {fds281881}
}
@article{fds281875,
Author = {Roth, T and Krystal, A and Steinberg, FJ and Singh, NN and Moline,
M},
Title = {Novel sublingual low-dose zolpidem tablet reduces latency to
sleep onset following spontaneous middle-of-the-night
awakening in insomnia in a randomized, double-blind,
placebo-controlled, outpatient study.},
Journal = {Sleep},
Volume = {36},
Number = {2},
Pages = {189-196},
Year = {2013},
Month = {February},
ISSN = {0161-8105},
url = {http://dx.doi.org/10.5665/sleep.2370},
Abstract = {STUDY OBJECTIVES: To evaluate efficacy and safety of 3.5-mg
zolpidem tartrate sublingual tablets (ZST) on latency to
sleep onset after middle-of-the-night (MOTN) awakenings in
patients with insomnia characterized by difficulty returning
to sleep after MOTN awakenings. DESIGN: Multicenter
randomized, double-blind, placebo-controlled,
parallel-group. SETTING: Outpatient. PATIENTS: There were
295 adults (median age 43 y; 68.1% female) with primary
insomnia and difficulty returning to sleep after MOTN
awakenings (three or more MOTN awakenings/wk during
screening). INTERVENTIONS: After a 2-wk, single-blind
placebo eligibility period, participants were randomized 1:1
to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28
nights. An interactive voice response system determined if
the study drug could be taken and recorded sleep/wake
efficacy measures. RESULTS: ZST significantly (P < 0.0001)
decreased latency to sleep onset over 4 wk (baseline 68.1
min; ZST 38.2 min) compared with placebo (baseline 69.4 min;
placebo 56.4 min). Ratings of morning sleepiness/alertness
significantly (P = 0.0041) favored the ZST group on nights
medication was taken but not on other nights. Participants
in the ZST group took the study drug on 62% of nights during
the 4 wk; members of the placebo group took study medication
on 64% of nights. Adverse events were generally mild and at
the same rate (19.3% of participants) in both groups. There
were no treatment-related serious adverse events (SAEs), and
one adverse event-related study discontinuation from the
placebo group. Dosing/week did not increase across the
study. CONCLUSIONS: 3.5 mg ZST used as needed significantly
reduced latency to return to sleep in comparison with
placebo in these patients with insomnia. Sleep quality was
improved, and morning sleepiness/alertness scores also
improved. ZST was well tolerated. These data demonstrate the
utility of a sleep-promoting agent when used as needed in
the MOTN. CLINICAL TRIALS REGISTRATION: NCT00466193: "A
Study of Zolpidem Tartrate Tablet in Adult Patients with
Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2},
Doi = {10.5665/sleep.2370},
Key = {fds281875}
}
@article{fds281948,
Author = {Rosenquist, PB and Krystal, A and Heart, KL and Demitrack, MA and McCall, WV},
Title = {Left dorsolateral prefrontal transcranial magnetic
stimulation (TMS): sleep factor changes during treatment in
patients with pharmacoresistant major depressive
disorder.},
Journal = {Psychiatry Research},
Volume = {205},
Number = {1-2},
Pages = {67-73},
Year = {2013},
Month = {January},
ISSN = {0165-1781},
url = {http://dx.doi.org/10.1016/j.psychres.2012.09.011},
Abstract = {As they alleviate major depressive disorder, antidepressant
therapies may improve associated sleep disturbances, but may
also have inherent sedating or activating properties. We
examined sleep changes during a multicenter,
sham-controlled, trial of transcranial magnetic stimulation
(TMS) therapy for pharmacoresistant MDD. Medication-free
outpatients (N=301) were randomized to receive active
(N=155) or sham (N=146) TMS for 6 weeks. Depression severity
was rated with the Montgomery-Asberg Depression Rating
Scale, the 24-item Hamilton Depression Scale (HAMD), and the
Inventory of Depressive Symptoms-Self Report (IDS-SR).
Assessments were performed at baseline, 2, 4, and 6 week
time points. Sleep was assessed using the HAMD and IDS-SR
sleep factors; comparison between treatment groups employed
ANCOVA model. No significant differences were identified
between the active and sham treatment groups in either the
HAMD or IDS-SR sleep factor scores at any time during
treatment. Sleep difficulty as an adverse event over the
length of the study did not differ between active and sham
treatment. Stratified by end of acute treatment responder
status, there was a statistically significant improvement in
both the HAMD sleep factor score and the IDS-SR sleep factor
during acute treatment in both the active and sham treatment
conditions. TMS exerts no intrinsic effect upon sleep in
patients with MDD.},
Doi = {10.1016/j.psychres.2012.09.011},
Key = {fds281948}
}
@article{fds281868,
Author = {Krystal, AD and Benca, RM and Kilduff, TS},
Title = {Understanding the sleep-wake cycle: sleep, insomnia, and the
orexin system.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {74 Suppl 1},
Pages = {3-20},
Year = {2013},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24107804},
Doi = {10.4088/JCP.13011su1c},
Key = {fds281868}
}
@article{fds281870,
Author = {Krystal, AD and Schopler, B and Kobbe, S and Williams, C and Rakatondrainibe, H and Yoder, AD and Klopfer, P},
Title = {The relationship of sleep with temperature and metabolic
rate in a hibernating primate.},
Journal = {Plos One},
Volume = {8},
Number = {9},
Pages = {e69914},
Year = {2013},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24023713},
Abstract = {STUDY OBJECTIVES: It has long been suspected that sleep is
important for regulating body temperature and
metabolic-rate. Hibernation, a state of acute hypothermia
and reduced metabolic-rate, offers a promising system for
investigating those relationships. Prior studies in
hibernating ground squirrels report that, although sleep
occurs during hibernation, it manifests only as non-REM
sleep, and only at relatively high temperatures. In our
study, we report data on sleep during hibernation in a
lemuriform primate, Cheirogaleus medius. As the only primate
known to experience prolonged periods of hibernation and as
an inhabitant of more temperate climates than ground
squirrels, this animal serves as an alternative model for
exploring sleep temperature/metabolism relationships that
may be uniquely relevant to understanding human physiology.
MEASUREMENTS AND RESULTS: We find that during hibernation,
non-REM sleep is absent in Cheirogaleus. Rather, periods of
REM sleep occur during periods of relatively high ambient
temperature, a pattern opposite of that observed in ground
squirrels. Like ground squirrels, however, EEG is marked by
ultra-low voltage activity at relatively low
metabolic-rates. CONCLUSIONS: These findings confirm a
sleep-temperature/metabolism link, though they also suggest
that the relationship of sleep stage with
temperature/metabolism is flexible and may differ across
species or mammalian orders. The absence of non-REM sleep
suggests that during hibernation in Cheirogaleus, like in
the ground squirrel, the otherwise universal non-REM sleep
homeostatic response is greatly curtailed or absent. Lastly,
ultra-low voltage EEG appears to be a cross-species marker
for extremely low metabolic-rate, and, as such, may be an
attractive target for research on hibernation
induction.},
Doi = {10.1371/journal.pone.0069914},
Key = {fds281870}
}
@article{fds281869,
Author = {Krystal, AD},
Title = {Sleep in Mood Disorders},
Pages = {675-681},
Publisher = {Elsevier},
Year = {2012},
Month = {December},
url = {http://dx.doi.org/10.1016/B978-1-4377-1703-7.10054-4},
Doi = {10.1016/B978-1-4377-1703-7.10054-4},
Key = {fds281869}
}
@article{fds281955,
Author = {Low, Y and Goforth, HW and Omonuwa, T and Preud'homme, X and Edinger, J and Krystal, A},
Title = {Comparison of polysomnographic data in age-, sex- and Axis I
psychiatric diagnosis matched HIV-seropositive and
HIV-seronegative insomnia patients.},
Journal = {Clin Neurophysiol},
Volume = {123},
Number = {12},
Pages = {2402-2405},
Year = {2012},
Month = {December},
ISSN = {1388-2457},
url = {http://dx.doi.org/10.1016/j.clinph.2012.05.004},
Abstract = {OBJECTIVE: There is a high prevalence of insomnia in
HIV-seropositive patients. Insomnia is associated with
poorer disease outcomes, cognitive impairment and
HIV-associated dementia. However there is limited data
characterizing the type of sleep disturbances, and the
cause. Previous studies report conflicting results, and
observed changes in the distribution of REM and SWS were
hypothesized to result from co-morbid mood disorders,
although this is not established. We carried out this study
to determine if there are differences in polysomnographic
(PSG) sleep data in age-, sex- and Axis I diagnoses- matched
HIV-seropositive and HIV-seronegative patients. METHODS:
Eighteen HIV-seropositive insomniacs were matched to
HIV-seronegative insomniacs based on age, sex and Axis I
diagnoses. Participants spent 2 consecutive nights in a
sleep lab recording of PSG data. RESULTS: Multivariate
analysis revealed an overall significant match-by-variable
interaction (p=0.0126). Follow-up analysis show that
compared to HIV-seronegative insomnia controls,
HIV-seropositive insomniacs have significantly longer SOL,
8% decreased sleep efficiency, and 8-10% decreased time
spent in REM sleep (p's<0.05). CONCLUSION: This study
provides preliminary evidence that even after accounting for
differences in age, sex and psychiatric diagnoses,
HIV-seropositive patients with insomnia have significantly
worse sleep than HIV-seronegative patients with insomnia.
SIGNIFICANCE: Unlike what previous authors have proposed,
our results do not support the view that comorbid
psychiatric disorders like depression are responsible for
the observed differences in PSG findings and the greater
incidence of insomnia, in HIV-seropositive patients when
compared with other groups of insomnia patients. This
suggests the presence of other etiologies including neuronal
damage, psychosocial stressors, or comorbid medical
conditions. Further studies are needed to determine the
extent to which these play a role in insomnia in the
HIV-seropositive population.},
Doi = {10.1016/j.clinph.2012.05.004},
Key = {fds281955}
}
@article{fds281954,
Author = {Krystal, AD},
Title = {Psychiatric disorders and sleep.},
Journal = {Neurol Clin},
Volume = {30},
Number = {4},
Pages = {1389-1413},
Year = {2012},
Month = {November},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23099143},
Abstract = {There is growing experimental evidence that the relationship
between psychiatric disorders and sleep is complex and
includes bidirectional causation. This article provides the
evidence that supports this point of view, reviewing data on
sleep disturbances seen in patients with psychiatric
disorders as well as data on the impact of sleep
disturbances on psychiatric conditions. Although much has
been learned about the psychiatric disorders-sleep
relationship, additional research is needed to better
understand the relationship. Such work promises to improve
comprehension of these phenomena and lead to better
treatment for the many patients with sleep disorders and
psychiatric disorders.},
Doi = {10.1016/j.ncl.2012.08.018},
Key = {fds281954}
}
@article{fds281878,
Author = {Krystal, AD and Roth, T and Simon, RD},
Title = {Shift work disorder case studies: applying management
principles in clinical practice.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {73},
Number = {8},
Pages = {e25},
Year = {2012},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22967784},
Abstract = {Shift work disorder (SWD) is a circadian rhythm sleep
disorder characterized by insomnia and excessive sleepiness.
SWD, which is estimated to affect 10% of people who work
night or rotating shifts, can have serious consequences such
as accidents, loss of productivity, and depression. By
enlisting the support of family, identifying and treating
comorbid sleep disorders, and appropriately timing light and
dark exposure (supplemented by melatonin), clinicians can
help many shift workers improve their ability to sleep,
maintain wakefulness, and possibly decrease other adverse
effects of shift work. More aggressive treatment strategies
and referral to a sleep specialist should be considered for
patients who do not respond to these simple
measures.},
Doi = {10.4088/jcp.11073br4},
Key = {fds281878}
}
@article{fds281953,
Author = {Krystal, AD and Huang, H and Zummo, J and Grinnell, T and Marshall,
RD},
Title = {A WASO sub-group analysis of a 6-month study of eszopiclone
3 mg.},
Journal = {Sleep Med},
Volume = {13},
Number = {6},
Pages = {691-696},
Year = {2012},
Month = {June},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22465450},
Abstract = {BACKGROUND: Insomnia marked by sleep maintenance difficulty
is extremely prevalent. Yet, problems staying asleep have
been relatively neglected as a research focus compared to
problems falling asleep. Insomnia treatment studies
typically have not required participants to have a problem
specifically with sleep maintenance. It is possible that
exclusion of such subjects limits the detection of treatment
effects in the overall trial in general, and of effects on
sleep maintenance specifically. In order to address these
issues we conducted a post hoc analysis of a 6-month
placebo-controlled trial in which there were no inclusion
criteria that specified sleep maintenance difficulties to
assess the variable effects of baseline wake time after
sleep onset (WASO - the primary maintenance measure) on the
efficacy of eszopiclone 3mg. METHODS: Patients diagnosed
with chronic primary insomnia were randomized to eszopiclone
3mg (n=593) or placebo (n=195) nightly for six months. The
present analyses of this study consisted of: (1)
determination of the distribution of baseline WASO; (2)
continuous analysis of the relationship between baseline
WASO severity and drug-placebo difference at month 1 and 6;
and (3) categorical efficacy analyses of subgroups delimited
by the following WASO thresholds: 0, 30, 45, 60, and 90 min.
RESULTS: The baseline WASO distribution was: ≤ 30=32.2%;
>0 to ≤ 45=41.5%; >30 to ≤ 90=33.0%; >45 to ≤
90=23.7%; >90=22.6%. A relationship between greater baseline
WASO severity and a significantly greater drug-placebo
difference in efficacy for WASO was evident in both
continuous and categorical analyses. Eszopiclone was found
to have significant sleep maintenance efficacy at each time
point across the entire range of WASO severity studied.
CONCLUSIONS: As illustrated in this analysis, a significant
proportion of chronic insomnia patients in efficacy trials
that select on the basis of sleep onset latency and total
sleep time criteria may have normative-range WASO. However,
even in the subgroup with minimal WASO there was a
significant sleep maintenance effect. The absence of any
sleep maintenance effect in a drug trial may reflect the
inclusion of relatively many insomnia patients with no
baseline WASO abnormality. However, treatments with
therapeutic effects on sleep maintenance, can still
demonstrate improvement in sleep maintenance, even in a
population not selected for this type of sleep problem, if
adequately powered. Future clinical trials intending to
examine sleep maintenance should employ WASO selection
criteria that would ensure sufficient power to detect a
sleep maintenance effect. Drug-placebo difference increased
as a function of baseline WASO severity, suggesting that
eszopiclone's clinical effectiveness for insomnia may be
enhanced in patients with more severe sleep maintenance
symptoms.},
Doi = {10.1016/j.sleep.2012.01.010},
Key = {fds281953}
}
@article{fds281952,
Author = {Ohayon, MM and Mahowald, MW and Dauvilliers, Y and Krystal, AD and Léger, D},
Title = {Prevalence and comorbidity of nocturnal wandering in the
U.S. adult general population.},
Journal = {Neurology},
Volume = {78},
Number = {20},
Pages = {1583-1589},
Year = {2012},
Month = {May},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22585435},
Abstract = {OBJECTIVE: To assess the prevalence and comorbid conditions
of nocturnal wandering with abnormal state of consciousness
(NW) in the American general population. METHODS:
Cross-sectional study conducted with a representative sample
of 19,136 noninstitutionalized individuals of the U.S.
general population ≥18 years old. The Sleep-EVAL expert
system administered questions on life and sleeping habits;
health; and sleep, mental, and organic disorders (DSM-IV-TR;
International Classification of Sleep Disorders, version 2;
International Classification of Diseases-10). RESULTS:
Lifetime prevalence of NW was 29.2% (95% confidence interval
[CI] 28.5%-29.9%). In the previous year, NW was reported by
3.6% (3.3%-3.9%) of the sample: 1% had 2 or more episodes
per month and 2.6% had between 1 and 12 episodes in the
previous year. Family history of NW was reported by 30.5% of
NW participants. Individuals with obstructive sleep apnea
syndrome (odds ratio [OR] 3.9), circadian rhythm sleep
disorder (OR 3.4), insomnia disorder (OR 2.1), alcohol
abuse/dependence (OR 3.5), major depressive disorder (MDD)
(OR 3.5), obsessive-compulsive disorder (OCD) (OR 3.9), or
using over-the-counter sleeping pills (OR 2.5) or selective
serotonin reuptake inhibitor (SSRI) antidepressants (OR 3.0)
were at higher risk of frequent NW episodes (≥2
times/month). CONCLUSIONS: With a rate of 29.2%, lifetime
prevalence of NW is high. SSRIs were associated with an
increased risk of NW. However, these medications appear to
precipitate events in individuals with a prior history of
NW. Furthermore, MDD and OCD were associated with
significantly greater risk of NW, and this was not due to
the use of psychotropic medication. These psychiatric
associations imply an increased risk due to sleep
disturbance.},
Doi = {10.1212/WNL.0b013e3182563be5},
Key = {fds281952}
}
@article{fds281963,
Author = {Flink, BJ and Rivelli, SK and Cox, EA and White, WD and Falcone, G and Vail, TP and Young, CC and Bolognesi, MP and Krystal, AD and Trzepacz,
PT and Moon, RE and Kwatra, MM},
Title = {Obstructive sleep apnea and incidence of postoperative
delirium after elective knee replacement in the nondemented
elderly.},
Journal = {Anesthesiology},
Volume = {116},
Number = {4},
Pages = {788-796},
Year = {2012},
Month = {April},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22337162},
Abstract = {BACKGROUND: Postoperative delirium, a common complication in
the elderly, can occur following any type of surgery and is
associated with increased morbidity and mortality; it may
also be associated with subsequent cognitive problems.
Effective therapy for postoperative delirium remains elusive
because the causative factors of delirium are likely
multiple and varied. METHODS: Patients 65 yr or older
undergoing elective knee arthroplasty were prospectively
evaluated for postoperative Diagnostic and Statistical
Manual of Mental Disorders-IV delirium. Exclusion criteria
included dementia, mini-mental state exam score less than
24, delirium, clinically significant central nervous
system/neurologic disorder, current alcoholism, or any
serious psychiatric disorder. Delirium was assessed on
postoperative days 2 and 3 using standardized scales.
Patients' preexisting medical conditions were obtained from
medical charts. The occurrence of obstructive sleep apnea
was confirmed by contacting patients to check their
polysomnography records. Data were analyzed using Pearson
chi-square or Wilcoxon rank sum tests and multiple logistic
regressions adjusted for effects of covariates. RESULTS: Of
106 enrolled patients, 27 (25%) developed postoperative
delirium. Of the 15 patients with obstructive sleep apnea,
eight (53%) experienced postoperative delirium, compared
with 19 (20%) of the patients without obstructive sleep
apnea (P = 0.0123, odds ratio: 4.3). Obstructive sleep apnea
was the only statistically significant predictor of
postoperative delirium in multivariate analyses.
CONCLUSIONS: This is the first prospective study employing
validated measures of delirium to identify an association
between preexisting obstructive sleep apnea and
postoperative delirium.},
Doi = {10.1097/ALN.0b013e31824b94fc},
Key = {fds281963}
}
@article{fds281950,
Author = {Carney, CE and Buysse, DJ and Ancoli-Israel, S and Edinger, JD and Krystal, AD and Lichstein, KL and Morin, CM},
Title = {The consensus sleep diary: standardizing prospective sleep
self-monitoring.},
Journal = {Sleep},
Volume = {35},
Number = {2},
Pages = {287-302},
Year = {2012},
Month = {February},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22294820},
Abstract = {STUDY OBJECTIVES: To present an expert consensus,
standardized, patient-informed sleep diary. METHODS AND
RESULTS: Sleep diaries from the original expert panel of 25
attendees of the Pittsburgh Assessment Conference(1) were
collected and reviewed. A smaller subset of experts formed a
committee and reviewed the compiled diaries. Items deemed
essential were included in a Core sleep diary, and those
deemed optional were retained for an expanded diary.
Secondly, optional items would be available in other
versions. A draft of the Core and optional versions along
with a feedback questionnaire were sent to members of the
Pittsburgh Assessment Conference. The feedback from the
group was integrated and the diary drafts were subjected to
6 focus groups composed of good sleepers, people with
insomnia, and people with sleep apnea. The data were
summarized into themes and changes to the drafts were made
in response to the focus groups. The resultant draft was
evaluated by another focus group and subjected to lexile
analyses. The lexile analyses suggested that the Core diary
instructions are at a sixth-grade reading level and the Core
diary was written at a third-grade reading level.
CONCLUSIONS: The Consensus Sleep Diary was the result of
collaborations with insomnia experts and potential users.
The adoption of a standard sleep diary for insomnia will
facilitate comparisons across studies and advance the field.
The proposed diary is intended as a living document which
still needs to be tested, refined, and validated.},
Doi = {10.5665/sleep.1642},
Key = {fds281950}
}
@article{fds281951,
Author = {Krystal, AD},
Title = {How the circadian rhythm affects sleep, wakefulness, and
overall health: background for understanding shift work
disorder.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {73},
Number = {2},
Pages = {e05},
Year = {2012},
Month = {February},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22401482},
Abstract = {It is estimated that 15 to 25% of the U.S. labor force works
night, evening, or rotating shifts. These non-traditional
schedules can affect the circadian rhythm, a self-sustained
rhythm of biological processes that plays an important role
in modulating sleep/wake function, resulting in circadian
rhythm sleep disorder, shift work type, usually referred to
as shift work disorder. The disorder consists of a constant
or recurrent pattern of sleep interruption that results in
insomnia when sleep is needed and excessive sleepiness
during waking hours. Clinicians need more information about
the role of the circadian rhythm in human functioning as
well as the pathophysiology, prevalence, and consequences of
shift work disorder, so that they can recognize and diagnose
this problem in clinical practice.},
Doi = {10.4088/jcp.11073br1},
Key = {fds281951}
}
@article{fds281949,
Author = {Ulmer, CS and Sutherland, M and Edinger, JD and Davidson, J and Connor,
KM and Zhang, W and Krystal, A},
Title = {REM sleep bout duration and frequency in
PTSD},
Journal = {Journal of Aggression, Maltreatment & Trauma},
Volume = {21},
Number = {1},
Pages = {67-76},
Publisher = {Informa UK Limited},
Year = {2012},
Month = {January},
ISSN = {1092-6771},
url = {http://dx.doi.org/10.1080/10926771.2012.630339},
Abstract = {The few pharmacological treatments shown to be effective in
reducing sleep disturbance in posttraumatic stress disorder
(PTSD) might work through normalization of rapid eye
movement (REM). However, evidence of REM sleep disturbance
in PTSD has been inconsistent and the definition of REM bout
has varied as well. In this study, we compared
polysomnographic findings in adults with PTSD to both normal
sleepers and insomniacs. We found no differences between
those with and without PTSD on REM bout frequency or
duration. We did, however, find gender differences within
our PTSD sample as consistent with a previous review
suggesting that males with PTSD are more likely to
demonstrate REM sleep disturbance. Consensus on REM bout
definition is needed, in addition to studies powered to
detect gender differences. Copyright © 2012 Taylor &
Francis Group, LLC.},
Doi = {10.1080/10926771.2012.630339},
Key = {fds281949}
}
@article{fds281879,
Author = {Krystal, AD and McCall, WV and Fava, M and Joffe, H and Soares, CN and Huang, H and Grinell, T and Zummo, J and Spalding, W and Marshall,
R},
Title = {Eszopiclone treatment for insomnia: effect size comparisons
in patients with primary insomnia and insomnia with medical
and psychiatric comorbidity.},
Journal = {The Primary Care Companion for Cns Disorders},
Volume = {14},
Number = {4},
Year = {2012},
ISSN = {2155-7772},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23251857},
Abstract = {OBJECTIVE: The purpose of this post hoc analysis was to
compare the treatment effect size of eszopiclone 3 mg for
insomnia in patients with a diagnosis of primary insomnia
and in several of the psychiatric and medical conditions
that are most commonly comorbid with insomnia. METHOD: Data
were analyzed from 5 large, multicenter, randomized,
double-blind, placebo-controlled studies of adult
outpatients of at least 1 month duration published between
2006 and 2009. Diary-derived indices of sleep and daytime
functioning and the Insomnia Severity Index were compared
for patients with primary insomnia (DSM-IV-TR criteria, n =
828) and for those with insomnia comorbid with major
depressive disorder (MDD, DSM-IV-TR criteria, n = 545),
generalized anxiety disorder (GAD, DSM-IV-TR criteria, n =
595), perimenopause/postmenopause (Stages of Reproductive
Aging Workshop criteria, n = 410), and rheumatoid arthritis
(American College of Rheumatology criteria, n = 153). Cohen
d effect sizes were calculated for each individual study as
the between-treatment difference score divided by the pooled
standard deviation. RESULTS: Effect sizes ranged from 0.40
to 0.69 (small-medium) as early as week 1 and were
maintained at 0.26-0.63 at week 4 for sleep latency, wake
time after sleep onset, and total sleep time. Sleep latency
and total sleep time effect sizes increased from week 1 to
week 4 in the primary insomnia group. At week 4, effect
sizes on all 3 parameters and the Insomnia Severity Index
tended to be highest for the primary insomnia patients and
tended to be lowest for patients with comorbid GAD and MDD.
The effect sizes for daytime functioning were small for all
insomnia patient groups. CONCLUSIONS: Eszopiclone 3 mg is an
effective treatment for insomnia across 5 clinically diverse
patient populations; however, magnitude of effect is
mediated by underlying comorbidity and their treatments,
with largest measures of effect seen in primary insomnia and
lowest in MDD and GAD. These consistent results, and the
fact that clinical trials were conducted in patients being
treated as appropriate for their comorbid clinical
conditions, support the results' real-world generalizability
and utility to clinical practice.},
Doi = {10.4088/PCC.11m01296},
Key = {fds281879}
}
@article{fds281956,
Author = {Krystal, AD and Sutherland, J and Hochman, DW},
Title = {Loop diuretics have anxiolytic effects in rat models of
conditioned anxiety.},
Journal = {Plos One},
Volume = {7},
Number = {4},
Pages = {e35417},
Year = {2012},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22514741},
Abstract = {A number of antiepileptic medications that modulate GABA(A)
mediated synaptic transmission are anxiolytic. The loop
diuretics furosemide (Lasix) and bumetanide (Bumex) are
thought to have antiepileptic properties. These drugs also
modulate GABA(A) mediated signalling through their
antagonism of cation-chloride cotransporters. Given that
loop diuretics may act as antiepileptic drugs that modulate
GABAergic signalling, we sought to investigate whether they
also mediate anxiolytic effects. Here we report the first
investigation of the anxiolytic effects of these drugs in
rat models of anxiety. Furosemide and bumetanide were tested
in adult rats for their anxiolytic effects using four
standard anxiety models: 1) contextual fear conditioning; 2)
fear-potentiated startle; 3) elevated plus maze, and 4)
open-field test. Furosemide and bumetanide significantly
reduced conditioned anxiety in the contextual
fear-conditioning and fear-potentiated startle models. At
the tested doses, neither compound had significant
anxiolytic effects on unconditioned anxiety in the elevated
plus maze and open-field test models. These observations
suggest that loop diuretics elicit significant anxiolytic
effects in rat models of conditioned anxiety. Since loop
diuretics are antagonists of the NKCC1 and KCC2
cotransporters, these results implicate the cation-chloride
cotransport system as possible molecular mechanism involved
in anxiety, and as novel pharmacological target for the
development of anxiolytics. In view of these findings, and
since furosemide and bumetanide are safe and well tolerated
drugs, the clinical potential of loop diuretics for treating
some types of anxiety disorders deserves further
investigation.},
Doi = {10.1371/journal.pone.0035417},
Key = {fds281956}
}
@article{fds281946,
Author = {Low, Y and Preud'homme, X and Goforth, HW and Omonuwa, T and Krystal,
AD},
Title = {The association of fatigue with depression and insomnia in
HIV-seropositive patients: a pilot study.},
Journal = {Sleep},
Volume = {34},
Number = {12},
Pages = {1723-1726},
Year = {2011},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22131611},
Abstract = {OBJECTIVE: Fatigue is a pervasive symptom associated with
HIV, resulting in significant functioning impairment; but
little is known about its etiology or treatment. In patients
with primary insomnia, data have shown improvement in
fatigue following successful treatment of insomnia. However,
little is known about the role of insomnia in patients with
fatigue in HIV. This manuscript seeks to test the hypothesis
that insomnia severity is correlated with increased fatigue
in HIV-seropositive patients. METHODS: Fifty-seven
ambulatory HIV-seropositive patients, aged 18-60 years, with
a DSM-IV-TR diagnosis of insomnia, were administered the
Insomnia Severity Index (ISI), Piper Fatigue Scale (PFS),
Hospital Anxiety and Depression scale, and Hamilton
Depression Rating Scale (HAM-D). Their most recent CD4 count
and time since diagnosis of HIV were recorded. Regression
analysis was carried out with PFS as the dependent variable.
RESULTS: A higher ISI score correlated with higher PFS
score, (R2 = 0.1713, P = 0.0042). Overall depression
severity was not significantly correlated with PFS score,
except in the most severely depressed subgroup, in which the
HADS depression score was the strongest predictor of PFS (R2
= 0.182, P = 0.0009). In participants without depression,
ISI accounted for most of the variance in fatigue (R2 =
0.6035, P = 0.0011). CONCLUSIONS: Greater insomnia severity
is associated with greater fatigue severity in HIV
seropositive patients. Depression may contribute to both
fatigue and insomnia. In the absence of depression, the
treatment of insomnia may emerge as a treatment strategy to
help alleviate fatigue. Further studies are needed to
confirm these data. CLINICAL TRIAL INFORMATION: Clinical
Trials.Gov: The Treatment of Insomnia in Patients with HIV
Disease. Registry Number: NCT00465972. URL:
http://www.clinicaltrials.gov/ct2/show/NCT00465972?term =
HIV+insomnia&rank = 1.},
Doi = {10.5665/sleep.1446},
Key = {fds281946}
}
@article{fds281947,
Author = {Palmese, LB and DeGeorge, PC and Ratliff, JC and Srihari, VH and Wexler,
BE and Krystal, AD and Tek, C},
Title = {Insomnia is frequent in schizophrenia and associated with
night eating and obesity.},
Journal = {Schizophrenia Research},
Volume = {133},
Number = {1-3},
Pages = {238-243},
Year = {2011},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21856129},
Abstract = {BACKGROUND: Sleep difficulties are common in schizophrenia,
however these complaints are often overshadowed by more
prominent clinical concerns. The point prevalence of
insomnia in this population is not well documented. Poor
sleep is associated with lower quality of life, impaired
cognition, and weight gain. OBJECTIVES: The objectives of
this study are to evaluate the prevalence of insomnia in
schizophrenia and to explore the relationship of sleep to
cognition, quality of life, and clinical variables. METHOD:
175 outpatients with schizophrenia or schizoaffective
disorder were assessed for insomnia. Participants were
evaluated for sleep difficulties, sleep patterns, body mass
index, and psychiatric symptoms. Participants were also
administered a brief cognitive assessment of processing
speed. RESULTS: 44% of the sample currently met the criteria
for clinical insomnia. An additional 4% were successfully
treated with medications. Insomnia was associated with
depression and was an independent predictor of lower quality
of life. Insomnia was also associated with high rates of
night eating and patients with severe insomnia were
significantly more obese. The type of antipsychotic did not
account for the difference in body mass index. No difference
between group means in cognition was detected, although
those with severe insomnia did perform least well.
CONCLUSION: Clinical insomnia in outpatients with
schizophrenia is highly prevalent and has a negative impact
on quality of life and psychiatric symptoms. This study
offers additional support to the association between poor
sleep and higher weight, as well as indicating a potential
link to night eating in this population. Assessment for
sleep difficulties should be a routine part of clinical
care.},
Doi = {10.1016/j.schres.2011.07.030},
Key = {fds281947}
}
@article{fds281945,
Author = {Rose, JE and McClernon, FJ and Froeliger, B and Behm, FM and Preud'homme, X and Krystal, AD},
Title = {Repetitive transcranial magnetic stimulation of the superior
frontal gyrus modulates craving for cigarettes.},
Journal = {Biol Psychiatry},
Volume = {70},
Number = {8},
Pages = {794-799},
Year = {2011},
Month = {October},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21762878},
Abstract = {BACKGROUND: Previous functional magnetic resonance imaging
studies have shown strong correlations between cue-elicited
craving for cigarettes and activation of the superior
frontal gyrus (SFG). Repetitive transcranial magnetic
stimulation (rTMS) offers a noninvasive means to reversibly
affect brain cortical activity, which can be applied to
testing hypotheses about the causal role of SFG in
modulating craving. METHODS: Fifteen volunteer smokers were
recruited to investigate the effects of rTMS on subjective
responses to smoking versus neutral cues and to controlled
presentations of cigarette smoke. On different days,
participants were exposed to three conditions: 1)
high-frequency (10 Hz) rTMS directed at the SFG; 2)
low-frequency (1 Hz) rTMS directed at the SFG; and 3)
low-frequency (1 Hz) rTMS directed at the motor cortex
(control condition). RESULTS: Craving ratings in response to
smoking versus neutral cues were differentially affected by
the 10-Hz versus 1-Hz SFG condition. Craving after smoking
cue presentations was elevated in the 10-Hz SFG condition,
whereas craving after neutral cue presentations was reduced.
Upon smoking in the 10-Hz SFG condition, ratings of
immediate craving reduction as well as the intensity of
interoceptive airway sensations were also attenuated.
CONCLUSIONS: These results support the view that the SFG
plays a role in modulating craving reactivity; moreover, the
results suggest that the SFG plays a role in both excitatory
and inhibitory influences on craving, consistent with prior
research demonstrating the role of the prefrontal cortex in
the elicitation as well as inhibition of drug-seeking
behaviors.},
Doi = {10.1016/j.biopsych.2011.05.031},
Key = {fds281945}
}
@article{fds281943,
Author = {Krystal, AD and Lankford, A and Durrence, HH and Ludington, E and Jochelson, P and Rogowski, R and Roth, T},
Title = {Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep
laboratory trial in adults with chronic primary
insomnia.},
Journal = {Sleep},
Volume = {34},
Number = {10},
Pages = {1433-1442},
Year = {2011},
Month = {October},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21966075},
Abstract = {STUDY OBJECTIVES: To evaluate the efficacy and safety of
doxepin (DXP) 3 mg and 6 mg in adults diagnosed with primary
insomnia. DESIGN AND METHODS: The study was a randomized,
double-blind, parallel-group, placebo-controlled trial.
Patients meeting DSM-IV-TR criteria for primary insomnia
were randomized to 35 days of nightly treatment with DXP 3
mg (n=75), DXP 6 mg (n=73), or placebo (PBO; n=73), followed
by 2 nights of single-blind PBO to evaluate discontinuation
(DC) effects. Efficacy was assessed using polysomnography
(PSG) and patient reports. Efficacy data were examined for
Night (N) 1, N15, and N29. Safety assessments were conducted
throughout the study. RESULTS: Compared with PBO, DXP 3 and
6 mg significantly improved wake time after sleep onset
(WASO) on N1 (3 mg and 6 mg; P<0.0001), N15 (3 mg P=0.0025;
6 mg P=0.0009), and N29 (3 mg P=0.0248; 6 mg P=0.0009),
latency to persistent sleep (LPS) on N1 (3 mg P=0.0047; 6 mg
P=0.0007), and total sleep time (TST) on N1 (3 mg and 6 mg
P<0.0001), N15 (6 mg P=0.0035), and N29 (3 mg P=0.0261; 6 mg
P<0.0001). In terms of early morning awakenings, DXP 3 and 6
mg demonstrated significant improvements in SE in the final
quarter of the night on N1, N15, and N29, with the exception
of 3 mg on N29 (P=0.0691). Rates of discontinuation were
low, and the safety profiles were comparable across the 3
treatment groups. There were no significant next-day
residual effects, and there were no spontaneous reports of
memory impairment, complex sleep behaviors, anticholinergic
effects, weight gain, or increased appetite. Additionally,
there was no evidence of rebound insomnia after DXP
discontinuation. CONCLUSIONS: Five weeks of nightly
administration of DXP 3 mg and 6 mg to adults with chronic
primary insomnia resulted in significant and sustained
improvements in sleep maintenance and early morning
awakenings (with the exception of SE in the final quarter of
the night on N29 for 3 mg [P=0.0691]). These sleep
improvements were not accompanied by next-day residual
effects or followed by rebound insomnia or withdrawal
effects upon discontinuation. These findings confirm the
unique profile of sleep maintenance efficacy and safety of
DXP observed in prior studies.},
Doi = {10.5665/SLEEP.1294},
Key = {fds281943}
}
@article{fds281962,
Author = {Edinger, JD and Wyatt, JK and Stepanski, EJ and Olsen, MK and Stechuchak, KM and Carney, CE and Chiang, A and Crisostomo, MI and Lineberger, MD and Means, MK and Radtke, RA and Wohlgemuth, WK and Krystal, AD},
Title = {Testing the reliability and validity of DSM-IV-TR and ICSD-2
insomnia diagnoses. Results of a multitrait-multimethod
analysis.},
Journal = {Arch Gen Psychiatry},
Volume = {68},
Number = {10},
Pages = {992-1002},
Year = {2011},
Month = {October},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21646568},
Abstract = {CONTEXT: Distinctive diagnostic classification schemes for
insomnia diagnoses are available, but the optimal insomnia
nosology has yet to be determined. OBJECTIVES: To test the
reliability and validity of insomnia diagnoses listed in the
American Psychiatric Association's DSM-IV-TR and the
International Classification of Sleep Disorders, second
edition (ICSD-2). DESIGN: Multitrait-multimethod correlation
design. SETTING: Two collaborating university medical
centers, with recruitment from January 2004 to February
2009. PARTICIPANTS: A total of 352 adult volunteers (235 of
whom were women) who met research diagnostic criteria for
insomnia disorder. MAIN OUTCOME MEASURES: Goodness-of-fit
ratings of 10 DSM-IV-TR and 37 ICSD-2 insomnia diagnoses for
each patient. Ratings were provided by 3 clinician pairs who
used distinctive assessment methods to derive diagnostic
impressions. Correlations computed within and across
clinician pairs were used to test reliability and validity
of diagnoses. RESULTS: Findings suggested that the
best-supported DSM-IV-TR insomnia categories were insomnia
related to another mental disorder, insomnia due to a
general medical condition, breathing-related sleep disorder,
and circadian rhythm sleep disorder. The category of primary
insomnia appeared to have marginal reliability and validity.
The best-supported ICSD-2 categories were the insomnias due
to a mental disorder and due to a medical condition,
obstructive sleep apnea, restless legs syndrome, idiopathic
insomnia, and circadian rhythm sleep disorder-delayed sleep
phase type. Psychophysiological insomnia and inadequate
sleep hygiene received much more variable support across
sites, whereas the diagnosis of paradoxical insomnia was
poorly supported. CONCLUSIONS: Both the DSM-IV-TR and ICSD-2
provide viable insomnia diagnoses, but findings support
selected subtypes from each of the 2 nosologies.
Nonetheless, findings regarding the frequently used
DSM-IV-TR diagnosis of primary insomnia and its related
ICSD-2 subtypes suggest that their poor reliability and
validity are perhaps due to significant overlap with
comorbid insomnia subtypes. Therefore, alternate diagnostic
paradigms should be considered for insomnia
classification.},
Doi = {10.1001/archgenpsychiatry.2011.64},
Key = {fds281962}
}
@article{fds281944,
Author = {Carney, CE and Moss, TG and Harris, AL and Edinger, JD and Krystal,
AD},
Title = {Should we be anxious when assessing anxiety using the Beck
Anxiety Inventory in clinical insomnia patients?},
Journal = {J Psychiatr Res},
Volume = {45},
Number = {9},
Pages = {1243-1249},
Year = {2011},
Month = {September},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21482427},
Abstract = {Assessing for clinical levels of anxiety is crucial, as
comorbid insomnias far outnumber primary insomnias (PI).
Such assessment is complex since those with Anxiety
Disorders (AD) and those with PI have overlapping symptoms.
Because of this overlap, we need studies that examine the
assessment of anxiety in clinical insomnia groups.
Participants (N = 207) were classified as having insomnia:
1) without an anxiety disorder (I-ND), or 2) with an anxiety
disorder (I-AD). Mean Beck Anxiety Inventory (BAI) item
responses were compared using multivariate analysis of
variance (MANOVA) and follow-up ANOVAs. As a validity check,
a receiver operating characteristic (ROC) curve analysis was
conducted to determine if the BAI suggested clinical cutoff
was valid for identifying clinical levels of anxiety in this
comorbid patient group. The I-ND had lower mean BAI scores
than I-AD. There were significant group differences on 12
BAI items. The ROC curve analysis revealed the suggested BAI
cutoff (≥16) had 55% sensitivity and 78% specificity.
Although anxiety scores were highest in those with insomnia
and an anxiety disorder, those with insomnia only had scores
in the mild range for anxiety. Nine items did not
distinguish between those insomnia sufferers with and
without an anxiety disorder. Additionally, published cutoffs
for the BAI were not optimal for identifying anxiety
disorders in those with insomnia. Such limitations must be
considered before using this measure in insomnia patient
groups. In addition, the poor specificity and high number of
overlapping symptoms between insomnia and anxiety highlight
the diagnostic challenges facing clinicians.},
Doi = {10.1016/j.jpsychires.2011.03.011},
Key = {fds281944}
}
@article{fds281942,
Author = {Krystal, AD},
Title = {A double-blind, placebo-controlled study of armodafinil for
excessive sleepiness in patients with treated obstructive
sleep apnea and comorbid depression (Journal of Clinical
Psychiatry (2010) 71, 1 (32-40))},
Journal = {The Journal of Clinical Psychiatry},
Volume = {72},
Number = {8},
Pages = {1157},
Year = {2011},
Month = {August},
ISSN = {0160-6689},
url = {http://dx.doi.org/10.4088/JCP.11lr07077a},
Doi = {10.4088/JCP.11lr07077a},
Key = {fds281942}
}
@article{fds281940,
Author = {Krystal, AD},
Title = {Recognition and assessment of shift work
disorder.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {72},
Number = {2},
Pages = {248-257},
Publisher = {Physicians Postgraduate Press, Inc},
Year = {2011},
Month = {February},
ISSN = {0160-6689},
url = {http://dx.doi.org/10.4088/JCP.10062ah1},
Abstract = {The circadian rhythm, a self-sustained rhythm of biological
processes observed in nearly all species, is determined by
both genetic and behavioral factors. It plays an important
role in coordinating and modulating sleep/wake function and
in many other biological processes. Disturbances of the
circadian rhythm cause misalignment among biological and
behavioral processes that can lead to disturbances in
sleep/wake function and other types of impaired functioning
and may affect our capacity to fight off disease. ©
Copyright 2011 Physicians Postgraduate Press,
Inc.},
Doi = {10.4088/JCP.10062ah1},
Key = {fds281940}
}
@article{fds281941,
Author = {Richey, SM and Krystal, AD},
Title = {Pharmacological advances in the treatment of
insomnia.},
Journal = {Curr Pharm Des},
Volume = {17},
Number = {15},
Pages = {1471-1475},
Year = {2011},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21476952},
Abstract = {Insomnia is a highly prevalent condition, and due to ongoing
demand from patients suffering with this condition, new
pharmacological treatments are actively being sought. As our
neurophysiological understanding of insomnia grows, so too
do the available treatment options. A significant advance in
the treatment of insomnia came with the development of the
nonbenzodiazepine hypnotic medications, zolpidem, zaleplon
and eszopiclone. These medications have shorter durations of
action than many traditional benzodiazepines and may be
associated with less risk of tolerance and abuse. They have
also been demonstrated to be helpful in cases in which
insomnia is comorbid with depression or anxiety, leading to
beneficial effects not only with sleep but also with mood
and anxiety symptoms. Melatonin, a naturally-occurring
substance intimately involved in the regulation of the
circadian rhythm, has also been explored as a hypnotic.
Little data to date support its use; however, there is
evidence that ramelteon, a melatonin agonist, may be helpful
for sleep initiation difficulties. Tri-cyclic
antidepressants have long been used for insomnia, but use
has been limited by unwanted anticholinergic side effects.
Low-dose doxepin, at doses of 3 and 6mg, has been
demonstrated to have the unique property among its class of
being free of anticholinergic effects at those doses. In
addition, it seems to have particular efficacy for sleep
maintenance insomnia, exhibiting the most robust effects in
the latter third of the night. The hypocretin/orexin system
has been identified as a possible target. Almorexant, a
hypocretin/orexin antagonist displayed evidence of efficacy
during Phase III clinical trials but these trials were
recently discontinued due to its side effect profile.
Another hypocretin/orexin antagonist with a different
mechanism of action, MK-4035, is presently in clinical
trials. Serotonin antagonists and inverse agonists have been
investigated; however, a recent trial with APD125 was
discontinued due to lack of efficacy. Sodium oxybate has
been used off-label for insomnia by some providers, although
data supporting its use are limited. While the
sleep-promoting effects of GABA(A) (nonbenzodiazepines and
benzodiazepines) enhancement is well-established, newer
research examining other mechanisms of action suggest that
agents which modulate the histaminergic, serotonergic,
melontonergic, and hypocretin/orexin and perhaps GABA-B
systems show promise.},
Doi = {10.2174/138161211796197052},
Key = {fds281941}
}
@article{fds281939,
Author = {Krystal, AD},
Title = {Antidepressant and Antipsychotic Drugs.},
Journal = {Sleep Med Clin},
Volume = {5},
Number = {4},
Pages = {571-589},
Year = {2010},
Month = {December},
ISSN = {1556-407X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21499530},
Doi = {10.1016/j.jsmc.2010.08.010},
Key = {fds281939}
}
@article{fds281937,
Author = {Krystal, AD and Durrence, HH and Scharf, M and Jochelson, P and Rogowski, R and Ludington, E and Roth, T},
Title = {Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week
Sleep Laboratory and Outpatient Trial of Elderly Subjects
with Chronic Primary Insomnia.},
Journal = {Sleep},
Volume = {33},
Number = {11},
Pages = {1553-1561},
Year = {2010},
Month = {November},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21102997},
Abstract = {STUDY OBJECTIVES: to evaluate the efficacy and safety of
doxepin 1 mg and 3 mg in elderly subjects with chronic
primary insomnia. DESIGN AND METHODS: the study was a
randomized, double-blind, parallel-group, placebo-controlled
trial. Subjects meeting DSM-IV-TR criteria for primary
insomnia were randomized to 12 weeks of nightly treatment
with doxepin (DXP) 1 mg (n = 77) or 3 mg (n = 82), or
placebo (PBO; n = 81). Efficacy was assessed using
polysomnography (PSG), patient reports, and clinician
ratings. Objective efficacy data are reported for Nights (N)
1, 29, and 85; subjective efficacy data during Weeks 1, 4,
and 12; and Clinical Global Impression (CGI) scale and
Patient Global Impression (PGI) scale data after Weeks 2, 4,
and 12 of treatment. Safety assessments were conducted
throughout the study. RESULTS: DXP 3 mg led to significant
improvement versus PBO on N1 in wake time after sleep onset
(WASO; P < 0.0001; primary endpoint), total sleep time (TST;
P < 0.0001), overall sleep efficiency (SE; P < 0.0001), SE
in the last quarter of the night (P < 0.0001), and SE in
Hour 8 (P < 0.0001). These improvements were sustained at
N85 for all variables, with significance maintained for
WASO, TST, overall SE, and SE in the last quarter of the
night. DXP 3 mg significantly improved patient-reported
latency to sleep onset (Weeks 1, 4, and 12), subjective TST
(Weeks 1, 4, and 12), and sleep quality (Weeks 1, 4, and
12). Several global outcome-related variables were
significantly improved, including the severity and
improvement items of the CGI (Weeks 2, 4, and 12), and all 5
items of the PGI (Week 12; 4 items after Weeks 2 and 4).
Significant improvements were observed for DXP 1 mg for
several measures including WASO, TST, overall SE, and SE in
the last quarter of the night at several time points. Rates
of discontinuation were low, and the safety profiles were
comparable across the 3 treatment groups. There were no
significant next-day residual effects; additionally, there
were no reports of memory impairment, complex sleep
behaviors, anticholinergic effects, weight gain, or
increased appetite. CONCLUSIONS: DXP 1 mg and 3 mg
administered nightly to elderly chronic insomnia patients
for 12 weeks resulted in significant and sustained
improvements in most endpoints. These improvements were not
accompanied by evidence of next-day residual sedation or
other significant adverse effects. DXP also demonstrated
improvements in both patient- and physician-based ratings of
global insomnia outcome. The efficacy of DXP at the doses
used in this study is noteworthy with respect to sleep
maintenance and early morning awakenings given that these
are the primary sleep complaints of the elderly. This study,
the longest placebo-controlled, double-blind,
polysomnographic trial of nightly pharmacotherapy for
insomnia in the elderly, provides the best evidence to date
of the sustained efficacy and safety of an insomnia
medication in older adults.},
Doi = {10.1093/sleep/33.11.1553},
Key = {fds281937}
}
@article{fds281938,
Author = {Wilson, SJ and Nutt, DJ and Alford, C and Argyropoulos, SV and Baldwin,
DS and Bateson, AN and Britton, TC and Crowe, C and Dijk, D-J and Espie,
CA and Gringras, P and Hajak, G and Idzikowski, C and Krystal, AD and Nash,
JR and Selsick, H and Sharpley, AL and Wade, AG},
Title = {British Association for Psychopharmacology consensus
statement on evidence-based treatment of insomnia,
parasomnias and circadian rhythm disorders.},
Journal = {J Psychopharmacol},
Volume = {24},
Number = {11},
Pages = {1577-1601},
Year = {2010},
Month = {November},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20813762},
Abstract = {Sleep disorders are common in the general population and
even more so in clinical practice, yet are relatively poorly
understood by doctors and other health care practitioners.
These British Association for Psychopharmacology guidelines
are designed to address this problem by providing an
accessible up-to-date and evidence-based outline of the
major issues, especially those relating to reliable
diagnosis and appropriate treatment. A consensus meeting was
held in London in May 2009. Those invited to attend included
BAP members, representative clinicians with a strong
interest in sleep disorders and recognized experts and
advocates in the field, including a representative from
mainland Europe and the USA. Presenters were asked to
provide a review of the literature and identification of the
standard of evidence in their area, with an emphasis on
meta-analyses, systematic reviews and randomized controlled
trials where available, plus updates on current clinical
practice. Each presentation was followed by discussion,
aimed to reach consensus where the evidence and/or clinical
experience was considered adequate or otherwise to flag the
area as a direction for future research. A draft of the
proceedings was then circulated to all participants for
comment. Key subsequent publications were added by the
writer and speakers at draft stage. All comments were
incorporated as far as possible in the final document, which
represents the views of all participants although the
authors take final responsibility for the
document.},
Doi = {10.1177/0269881110379307},
Key = {fds281938}
}
@article{fds281936,
Author = {Janicak, PG and Nahas, Z and Lisanby, SH and Solvason, HB and Sampson,
SM and McDonald, WM and Marangell, LB and Rosenquist, P and McCall, WV and Kimball, J and O'Reardon, JP and Loo, C and Husain, MH and Krystal, A and Gilmer, W and Dowd, SM and Demitrack, MA and Schatzberg,
AF},
Title = {Durability of clinical benefit with transcranial magnetic
stimulation (TMS) in the treatment of pharmacoresistant
major depression: assessment of relapse during a 6-month,
multisite, open-label study.},
Journal = {Brain Stimul},
Volume = {3},
Number = {4},
Pages = {187-199},
Year = {2010},
Month = {October},
ISSN = {1935-861X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20965447},
Abstract = {BACKGROUND: Although transcranial magnetic stimulation (TMS)
can be an effective acute antidepressant treatment, few
studies systematically examine persistence of benefit.
OBJECTIVE: We assessed the durability of antidepressant
effect after acute response to TMS in patients with major
depressive disorder (MDD) using protocol-specified
maintenance antidepressant monotherapy. METHODS: Three
hundred one patients were randomly assigned to active or
sham TMS in a 6-week, controlled trial. Nonresponders could
enroll in a second, 6-week, open-label study. Patients who
met criteria for partial response (i.e., >25% decrease from
the baseline HAMD 17) during either the sham-controlled or
open-label study (n = 142) were tapered off TMS over 3
weeks, while simultaneously starting maintenance
antidepressant monotherapy. Patients were then followed for
24 weeks in a naturalistic follow-up study examining the
long-term durability of TMS. During this durability study,
TMS was readministered if patients met prespecified criteria
for symptom worsening (i.e., a change of at least one point
on the CGI-S scale for 2 consecutive weeks). Relapse was the
primary outcome measure. RESULTS: Ten of 99 (10%;
Kaplan-Meier survival estimate = 12.9%) patients relapsed.
Thirty-eight (38.4%) patients met criteria for symptom
worsening and 32/38 (84.2%) reachieved symptomatic benefit
with adjunctive TMS. Safety and tolerability were similar to
acute TMS monotherapy. CONCLUSIONS: These initial data
suggest that the therapeutic effects of TMS are durable and
that TMS may be successfully used as an intermittent rescue
strategy to preclude impending relapse.},
Doi = {10.1016/j.brs.2010.07.003},
Key = {fds281936}
}
@article{fds281960,
Author = {Flynn, KE and Shelby, RA and Mitchell, SA and Fawzy, MR and Hardy, NC and Husain, AM and Keefe, FJ and Krystal, AD and Porter, LS and Reeve, BB and Weinfurt, KP},
Title = {Sleep-wake functioning along the cancer continuum: focus
group results from the Patient-Reported Outcomes Measurement
Information System (PROMIS(®)).},
Journal = {Psychooncology},
Volume = {19},
Number = {10},
Pages = {1086-1093},
Year = {2010},
Month = {October},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20013938},
Abstract = {OBJECTIVE: Cancer and its treatments disturb sleep-wake
functioning; however, there is little information available
on the characteristics and consequences of sleep problems
associated with cancer. As part of an effort to improve
measurement of sleep-wake functioning, we explored the scope
of difficulties with sleep in a diverse group of patients
diagnosed with cancer. METHODS: We conducted 10 focus groups
with patients recruited from the Duke University tumor
registry and oncology/hematology clinics. Separate groups
were held with patients scheduled to begin or currently
undergoing treatment for breast, prostate, lung, colorectal,
hematological, and other cancer types and with patients who
were in posttreatment follow-up. The content of the focus
group discussions was transcribed and analyzed for major
themes by independent coders. RESULTS: Participants not only
reported causes of sleep disturbance common in other
populations, such as pain and restless legs, but they also
reported causes that may be unique to cancer populations,
including abnormal dreams, anxiety about cancer diagnosis
and recurrence, night sweats, and problems with sleep
positioning. Many participants felt that sleep problems
reduced their productivity, concentration, social
interactions, and overall quality of life. Many also shared
beliefs about the increased importance of sleep when
fighting cancer. CONCLUSIONS: The findings underscore the
need for interventions that minimize the negative impact of
cancer and its treatments on sleep. This study will inform
efforts now underway to develop a patient-reported measure
of sleep-wake functioning that reflects the breadth of
concepts considered important by patients with
cancer.},
Doi = {10.1002/pon.1664},
Key = {fds281960}
}
@article{fds281934,
Author = {McCall, WV and Blocker, JN and D'Agostino, R and Kimball, J and Boggs,
N and Lasater, B and Haskett, R and Krystal, A and McDonald, WM and Rosenquist, PB},
Title = {Treatment of insomnia in depressed insomniacs: effects on
health-related quality of life, objective and self-reported
sleep, and depression.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {6},
Number = {4},
Pages = {322-329},
Year = {2010},
Month = {August},
ISSN = {1550-9389},
Abstract = {STUDY OBJECTIVES: Insomnia is associated with poor health
related quality of life (HRQOL) in depressed patients. Prior
clinical trials of hypnotic treatment of insomnia in
depressed patients have shown improvement in HRQOL, but in
these studies HRQOL was relegated to a secondary outcome,
and objective measures of sleep were not undertaken. DESIGN:
Double-blind, randomized, placebo-controlled clinical trial.
SETTING: Outpatient clinic and sleep laboratory. PATIENTS:
60 depressed, insomniac outpatients. INTERVENTIONS: One week
of open-label fluoxetine (FLX), followed by 8 more weeks of
FLX combined with either eszopiclone (ESZ) 3 mg or placebo
at bedtime. MEASUREMENTS: The primary HRQOL measure was the
daily living and role functioning subscale (DLRF) of the
Basis-32. Other measures included the Q-LES-Q, self-reported
sleep, PSG, actigraphy, depression severity (HRSD). RESULTS:
At the end of randomized treatment, patients receiving ESZ
had lower (better) DLRF scores (0.81 +/- 0.64) than those
receiving placebo (1.2 +/- 0.72), p = 0.01. The effect size
for DLRF was 0.62, indicating a moderate effect. An
advantage for ESZ was also seen in other measures of HRQOL,
and most assessments of antidepressant efficacy and sleep.
Women reported better end of treatment HRQOL scores than
men. CONCLUSIONS: ESZ treatment of insomnia in depressed
patients is associated with multiple favorable outcomes,
including superior improvement in HRQOL, depression
severity, and sleep.},
Key = {fds281934}
}
@article{fds281935,
Author = {Krystal, AD and Zammit, GK and Wyatt, JK and Quan, SF and Edinger, JD and White, DP and Chiacchierini, RP and Malhotra, A},
Title = {The effect of vestibular stimulation in a four-hour sleep
phase advance model of transient insomnia.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {6},
Number = {4},
Pages = {315-321},
Year = {2010},
Month = {August},
ISSN = {1550-9389},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20726278},
Abstract = {STUDY OBJECTIVES: To determine if vestibular stimulation is
an effective therapy for transient insomnia in a sleep phase
advance model. DESIGN: Multi-site, double-blind, randomized,
parallel-group, sham-controlled trial SETTING: This study
was carried out at 6 sites in the United States.
PARTICIPANTS: 198 healthy normal sleepers. INTERVENTIONS:
Bilateral electrical stimulation of the vestibular apparatus
of the inner ear via electrodes on the skin of the mastoid
process at a frequency of 0.5 Hz vs. sham stimulation.
RESULTS: We did not find a significant effect of treatment
on our primary outcome variable, latency to persistent sleep
onset (LPS). However, our planned analysis identified that
the mean latency to sleep onset on the multiple sleep
latency test was a significant covariate. This led us to
carry out post hoc analyses, which showed a significant
effect of treatment on LPS in those subjects with a mean
MSLT sleep onset latency > or = 14 minutes. CONCLUSIONS:
Vestibular stimulation did not have a therapeutic effect in
a model of transient insomnia in the overall population
studied. However, this study provides preliminary evidence
that vestibular stimulation may shorten sleep onset latency
compared with sham therapy in the subset of subjects with
mean MSLT sleep onset latency > or = 14 minutes.},
Key = {fds281935}
}
@article{fds281966,
Author = {Krystal, AD and Preud'homme, XA and Amundsen, CL and Webster,
GD},
Title = {Detrusor overactivity persisting at night and preceding
nocturia in patients with overactive bladder syndrome: a
nocturnal cystometrogram and polysomnogram
study.},
Journal = {The Journal of Urology},
Volume = {184},
Number = {2},
Pages = {623-628},
Year = {2010},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20639027},
Abstract = {PURPOSE: Nocturia, a common symptom of overactive bladder
syndrome, is associated with substantial adverse
consequences and yet its pathophysiology has hardly been
studied and the capacity to treat it remains limited. We
established methods to study the physiology of overactive
bladder associated nocturia and better understand this
phenomenon. MATERIALS AND METHODS: We recorded simultaneous,
time aligned, nocturnal cystometrogram and polysomnogram
data during a single night at a sleep laboratory in 9
patients with overactive bladder and detrusor overactivity
on daytime cystometrogram, in 10 patients with insomnia and
in 5 healthy controls. RESULTS: We safely recorded
simultaneous polysomnography/nocturnal cystometrography data
accurately during the sleep period. Nocturnal detrusor
overactivity occurred significantly less often in patients
with insomnia and controls than in patients with detrusor
overactivity plus overactive bladder (p = 0.02) and only in
the 10 minutes before nocturia events in the latter (0%, 0%
and 67%, respectively, p = 0.002). Patients with detrusor
overactivity plus overactive bladder were awake for a
shorter period before nocturia events (p <0.001) and had a
greater percent of nocturia associated awakenings. Patients
with insomnia had more awakenings unrelated to nocturia.
Nocturnal polyuria, another cause of nocturia, was not
significantly associated with nocturnal detrusor
overactivity. CONCLUSIONS: Sleep and bladder pressure
physiology may be safely monitored during the sleep period
accurately. Nocturnal detrusor overactivity occurs in
association with nocturia in most patients with detrusor
overactivity plus overactive bladder, does not generally
occur during sleep and is not due to sleep disturbance or
nocturnal polyuria. This study may provide a foundation for
research on overactive bladder related nocturia
pathophysiology and treatment.},
Doi = {10.1016/j.juro.2010.03.148},
Key = {fds281966}
}
@article{fds281933,
Author = {Krystal, AD},
Title = {In vivo evidence of the specificity of effects of GABA(A)
receptor modulating medications.},
Journal = {Sleep},
Volume = {33},
Number = {7},
Pages = {859-860},
Year = {2010},
Month = {July},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20614842},
Doi = {10.1093/sleep/33.7.859},
Key = {fds281933}
}
@article{fds281932,
Author = {Krystal, AD and Edinger, JD},
Title = {Sleep EEG predictors and correlates of the response to
cognitive behavioral therapy for insomnia.},
Journal = {Sleep},
Volume = {33},
Number = {5},
Pages = {669-677},
Year = {2010},
Month = {May},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20469809},
Abstract = {STUDY OBJECTIVES: Determine the relationship of non-rapid
eye movement (NREM) electroencephalographic (EEG) spectral
measures and the response to cognitive behavioral therapy
(CBT) in primary insomnia (PI). DESIGN: Patients with PI
were randomly assigned to CBT or a placebo intervention
(PC). Ambulatory polysomnography was performed before and
after treatment. SETTING: University medical center sleep
laboratory. PARTICIPANTS: Thirty PI patients with sleep
maintenance difficulty evident in subjective sleep measures.
INTERVENTIONS: CBT and PC. RESULTS: CBT led to a more rapid
decline in EEG delta power over the night, compared with PC.
This change was associated with subjective improvement in
response to CBT. Furthermore, lower pretreatment peak EEG
delta power in the first NREM cycle and a more gradual
decline in delta power predicted a better response to CBT.
Increased wake time during the day produced by CBT was
correlated with an increase in the steepness of the slope of
EEG delta power and subjective improvement. Traditional
polysomnography measures were associated with the subjective
CBT response to a greater degree among patients whose total
sleep time estimates better approximated
polysomnography-derived total sleep time. In contrast,
changes in all-night averaged NREM EEG spectral indices were
more strongly related to subjective improvement in
individuals who underestimated total sleep time to a greater
extent. CONCLUSIONS: CBT led to a more rapid decline in EEG
delta power over the night. This change is linked to the
therapeutic effect of CBT, which appears to occur in
conjunction with an increase in homeostatic sleep drive.
Traditional polysomnography indices and all-night averaged
NREM EEG measures appear to be related to subjective
improvements with CBT in subsets of patients with
PI.},
Doi = {10.1093/sleep/33.5.669},
Key = {fds281932}
}
@article{fds281930,
Author = {Ohayon, MM and Krystal, A and Roehrs, TA and Roth, T and Vitiello,
MV},
Title = {Using difficulty resuming sleep to define nocturnal
awakenings.},
Journal = {Sleep Med},
Volume = {11},
Number = {3},
Pages = {236-241},
Year = {2010},
Month = {March},
ISSN = {1389-9457},
url = {http://dx.doi.org/10.1016/j.sleep.2009.11.004},
Abstract = {OBJECTIVE: Nocturnal awakenings are one of the most
prevalent sleep disturbances in the general population.
Little is known, however, about the frequency of these
episodes and how difficulty resuming sleep once awakened
affects subjective sleep quality and quantity. METHOD: This
is a cross-sectional telephone study with a representative
sample consisting of 8937 non-institutionalized individuals
aged 18 or over living in Texas, New York and California.
The interviews included questions on sleeping habits,
health, sleep and mental disorders. Nocturnal awakenings
were evaluated according to their frequency per week and per
night, as well as their duration. RESULTS: A total of 35.5%
of the sample reported awakening at least three nights per
week. Of this 35.5%, 43% (15.2% of the total sample)
reported difficulty resuming sleep once awakened. More than
80% of subjects with insomnia symptoms (difficulty
initiating or maintaining sleep or non-restorative sleep)
also had nocturnal awakenings. Difficulty resuming sleep was
associated with subjective shorter sleep duration, poorer
sleep quality, greater daytime impairment, greater
consultations for sleep disturbances and greater likelihood
of receiving a sleep medication. CONCLUSIONS: Nocturnal
awakenings disrupt the sleep of about one-third of the
general population. Using difficulty resuming sleep
identifies individuals with significant daytime impairment
who are most likely to seek medical help for their sleep
disturbances. In the absence of other insomnia symptoms,
nocturnal awakenings alone are unlikely to be associated
with daytime impairments.},
Doi = {10.1016/j.sleep.2009.11.004},
Key = {fds281930}
}
@article{fds281928,
Author = {Ancoli-Israel, S and Krystal, AD and McCall, WV and Schaefer, K and Wilson, A and Claus, R and Rubens, R and Roth, T},
Title = {A 12-week, randomized, double-blind, placebo-controlled
study evaluating the effect of eszopiclone 2 mg on
sleep/wake function in older adults with primary and
comorbid insomnia.},
Journal = {Sleep},
Volume = {33},
Number = {2},
Pages = {225-234},
Year = {2010},
Month = {February},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20175406},
Abstract = {BACKGROUND: Longer-term pharmacologic studies for insomnia
in older individuals are sparse. OBJECTIVE: To evaluate the
efficacy and safety of 12 weeks of nightly eszopiclone in
elderly outpatients with insomnia. METHODS: Participants
(65-85 years) met DSM-IV-TR criteria for insomnia with total
sleep times (TST) < or = 6 h, and wake time after sleep
onset (WASO) > or = 45 min. Participants were randomized to
12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194),
followed by a 2-week single-blind placebo run-out.
Subject-reported measures of sleep (sTST, sleep latency
[sSL], sWASO) and daytime function (alertness,
concentration, wellbeing, ability to function) were
assessed. AEs were monitored. RESULTS: Subjects treated with
2 mg eszopiclone slept longer at night on average and at
every individual time point compared to baseline than
placebo subjects, as measured by TST over the 12-week
double-blind period (P < 0.0001). Mean sTST over the
double-blind period for eszopiclone-treated subjects was
360.08 min compared to 297.86 min at baseline, a mean change
of 63.24 min. Over the double-blind period,
eszopiclone-treated subjects also experienced a
significantly greater improvement in sSL compared to
placebo, with a mean decrease of 24.62 min versus a mean
decrease of 19.92 min, respectively (P = 0.0014).
Eszopiclone subjects also experienced a significantly
greater decrease in WASO (mean decrease of 36.4 min)
compared to placebo subjects (decrease of 14.8 min) (P <
0.0001). Post-discontinuation, sleep parameters were
statistically improved versus baseline for eszopiclone
(P-values < or = 0.01), indicating no rebound. The most
common AEs (> or = 5%) were headache (eszopiclone 13.9%,
placebo 12.4%), unpleasant taste (12.4%, 1.5%), and
nasopharyngitis (5.7%, 6.2%). CONCLUSION: In this Phase IV
trial of older adults with insomnia, eszopiclone
significantly improved patient-reported sleep and daytime
function relative to placebo. Improvements occurred within
the first week and were maintained for 3 months, with no
evidence of rebound insomnia following discontinuation. The
12 weeks of treatment were well tolerated. CLINICAL TRIAL
INFORMATION: A Long-Term Safety and Efficacy Study of
Eszopiclone in Elderly Subjects With Primary Chronic
Insomnia; Registration #NCT00386334; URL -
http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=eszopiclone&rank=24},
Doi = {10.1093/sleep/33.2.225},
Key = {fds281928}
}
@article{fds281929,
Author = {Krystal, AD and Harsh, JR and Yang, R and Rippon, GA and Lankford,
DA},
Title = {A double-blind, placebo-controlled study of armodafinil for
excessive sleepiness in patients with treated obstructive
sleep apnea and comorbid depression.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {71},
Number = {1},
Pages = {32-40},
Year = {2010},
Month = {January},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20051221},
Abstract = {OBJECTIVE: Treatment of excessive sleepiness in the context
of obstructive sleep apnea (OSA) may be particularly
difficult in those with depression because depression and/or
antidepressant medications may cause sleepiness and fatigue
in addition to that due to the OSA. This study evaluating
armodafinil, a nonamphetamine wakefulness-promoting
medication, is the first trial for treatment of excessive
sleepiness in patients with treated OSA and comorbid
depression. METHOD: Men and women with OSA diagnosed using
International Classification of Sleep Disorders criteria
being treated with continuous positive airway pressure and
comorbid major depressive disorder or dysthymic disorder
according to DSM-IV-TR criteria were enrolled into a
12-week, randomized, double-blind, parallel-group study
between September 2007 and March 2009 at 60 outpatient
sites. Patients maintained on stable monotherapy with a
serotonergic antidepressant and with a 17-item Hamilton
Depression Rating Scale score < 17 received placebo or
armodafinil (target dose: 200 mg once daily). Coprimary
outcomes were the proportion of patients with at least
minimal improvement on the Clinical Global Impression of
Change (CGI-C) as related to excessive sleepiness and mean
change from baseline in Maintenance of Wakefulness Test mean
sleep latency at final visit; the key secondary outcome was
mean change in the Epworth Sleepiness Scale score. RESULTS:
249 patients were enrolled: 125 in the armodafinil group and
124 in the placebo group. The proportion of patients with at
least minimal improvement on the CGI-C was statistically
significantly greater in the armodafinil group (69%)
compared with the placebo group (53%, P = .012). Mean (SD)
increase in Maintenance of Wakefulness Test sleep latency
was numerically but not significantly greater following
armodafinil (2.6 [7.1] min) versus placebo (1.1 [7.6] min, P
= .30) treatment. Mean decrease in Epworth Sleepiness Scale
score was greater in the armodafinil group (-6.3 [4.8]) than
in the placebo group (-4.8 [4.9], nominal P = .003).
Headache, dry mouth, and insomnia were the most common
adverse events occurring with armodafinil treatment. There
was no clinically significant effect on depression in either
group as measured by the Quick Inventory of Depressive
Symptomatology-Self-Report 16. CONCLUSIONS: Armodafinil
significantly improved overall clinical condition related to
excessive sleepiness as rated by the CGI-C and was well
tolerated in patients with treated OSA and comorbid
depression. TRIAL REGISTRATION: clinicaltrials.gov
Identifier: NCT00518986.},
Doi = {10.4088/JCP.09m05536gry},
Key = {fds281929}
}
@article{fds281931,
Author = {Ancoli-Lsrael, S and Krystal, AD},
Title = {Insomnia: A health care (gap that is growing)},
Journal = {Psychiatric Times},
Volume = {27},
Number = {SUPPL. APRIL},
Pages = {1-4},
Year = {2010},
Month = {January},
ISSN = {0893-2905},
Abstract = {Insomnia is a highly prevalent and costly condition. It is
underdiagnosed and many patients remain untreated. All
patients should be asked about their sleep-related health.
If the patient has sleep difficulties accompanied by
impairment in physical or cognitive function or quality of
life, medical intervention should be considered. Optimal
treatment requires formulating a diagnosis based on a
comprehensive medical/sleep history. Treatment should be
chosen in order to best address the identified type and
timing of the sleepwake disorder. The risk-benefit ratio of
any treatment must be considered in relationship to the
needs of the individual patient. Comorbid psychiatric
disorders are common and should be treated concomitantly
with insomnia. Nonpharmacologic therapies can be used as
first-line treatment and can be used in combination with
medication. Patients should be monitored for therapeutic
response and, if refractory, should be referred to a sleep
medicine specialist for further evaluation. When insomnia is
accurately diagnosed and effectively treated, the cycle of
compromised sleep and function is broken, sleep can be
restored, and patients can regain their quality of
life.},
Key = {fds281931}
}
@article{fds311712,
Author = {Edinger, JD and Wyatt, JK and Olsen, MK and Stechuchak, KM and Carney,
CE and Chiang, AA and Krystal, AD and Lineberger, MD and Means, MK and Radtke, RA},
Title = {UTILITY, VALIDITY, AND METHODOLOGICAL FACTORS INFLUENCING
ASSIGNMENT OF DSM-IV-TR INSOMNIA DIAGNOSES: CONSIDERATIONS
FOR DSM-V},
Journal = {Sleep},
Volume = {33},
Pages = {A191-A191},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001053&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311712}
}
@article{fds311713,
Author = {Edinger, JD and Green, MR and Prather, AA and Wyatt, JK and Olsen, MK and Stechuchak, KM and Carney, CE and Chiang, AA and Krystal, AD and Radtke,
RA},
Title = {VALIDITY AND RELIABILITY OF THE DSM-IV-TR AND ICSD-2
INSOMNIA NOSOLOGIES AMONG CAUCASIANS AND
AFRICAN-AMERICANS},
Journal = {Sleep},
Volume = {33},
Pages = {A209-A209},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001107&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311713}
}
@article{fds311664,
Author = {Preud'homme, XA and Amundsen, CL and Webster, GD and Krystal,
AD},
Title = {MONITORED NIGHTTIME BLADDER FUNCTION: COMPARISONS BETWEEN
PATIENTS WITH INSOMNIA AND THOSE WITH OVERACTIVE BLADDER
SYNDROME},
Journal = {Sleep},
Volume = {33},
Pages = {A293-A293},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001360&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311664}
}
@article{fds311666,
Author = {Preud'homme, XA and Amundsen, CL and Webster, GD and Krystal,
AD},
Title = {SELF-REPORTED SLEEP: HOW DO PATIENTS WITH OAB COMPARE TO
INSOMNIACS AND NORMAL SUBJECTS?},
Journal = {Sleep},
Volume = {33},
Pages = {A292-A292},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001359&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311666}
}
@article{fds311667,
Author = {Krystal, AD and Preud'homme, XA and Amundsen, CL and Webster,
GD},
Title = {NOCTURNAL DETRUSOR OVERACTIVITY IN OVERACTIVE BLADDER
SYNDROME: A NOCTURNAL CYSTOMETROGRAPHIC AND POLYSOMNOGRAPHIC
STUDY},
Journal = {Sleep},
Volume = {33},
Pages = {A293-A293},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001361&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311667}
}
@article{fds311694,
Author = {Krystal, AD and Harsh, J and Yang, R and Rippon, GA and Lankford,
A},
Title = {EFFECT OF ARMODAFINIL ON PATIENT FUNCTIONING AND FATIGUE: A
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
PARALLEL-GROUP STUDY IN PATIENTS WITH RESIDUAL EXCESSIVE
SLEEPINESS ASSOCIATED WITH TREATED OBSTRUCTIVE SLEEP APNEA
AND A COMORBID DEPRESSIVE DISORDER},
Journal = {Sleep},
Volume = {33},
Pages = {A7-A8},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208000015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311694}
}
@article{fds311699,
Author = {Low, Y and Omonuwa, T and Goforth, HW and Krystal,
AD},
Title = {INSOMNIA SEVERITY IN HIV-SEROPOSITIVE PATIENTS IS ASSOCIATED
WITH INCREASED FATIGUE},
Journal = {Sleep},
Volume = {33},
Pages = {A194-A194},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208001061&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311699}
}
@article{fds311700,
Author = {Low, Y and Suarez, EC and Omonuwa, T and Goforth, HW and Krystal,
AD},
Title = {A PILOT STUDY: IMPROVEMENT IN INSOMNIA SEVERITY IS
ASSOCIATED WITH DECREASED SOLUBLE CD4-LIGAND IN
HIV-SEROPOSITIVE PATIENTS},
Journal = {Sleep},
Volume = {33},
Pages = {A26-A27},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2010},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000208208000071&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311700}
}
@article{fds281927,
Author = {Krystal, AD},
Title = {The treatment of primary insomnia.},
Journal = {Cns Spectrums},
Volume = {14},
Number = {12 Suppl 13},
Pages = {6-10},
Year = {2009},
Month = {December},
ISSN = {1092-8529},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20448512},
Doi = {10.1017/s1092852900003953},
Key = {fds281927}
}
@article{fds281926,
Author = {Krystal, AD},
Title = {A compendium of placebo-controlled trials of the
risks/benefits of pharmacological treatments for insomnia:
the empirical basis for U.S. clinical practice.},
Journal = {Sleep Med Rev},
Volume = {13},
Number = {4},
Pages = {265-274},
Year = {2009},
Month = {August},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19153052},
Abstract = {For many years practitioners have had limited data from
double-blind, placebo-controlled studies to guide the types
of decision-making needed to optimally manage patients with
insomnia in clinical practice. However, in recent years
there has been a great increase in insomnia research studies
that address issues of clinical importance. This body of
work represents an increasingly useful empirical basis for
making clinical practice decisions. The purpose of this
article is to compile the body of work on the
pharmacological management of insomnia to make it available
in as accessible form as possible for optimal application in
clinical practice with the hopes that doing so will decrease
the gap separating the available research and the clinical
management of insomnia and, thereby, improve the care of the
many individuals who suffer from this condition. The review
of studies consists of the following sections: 1) basic
pharmacology; 2) double-blind, placebo-controlled trials in
adults with primary insomnia; 3) double-blind,
placebo-controlled trials in elderly patients with primary
insomnia; 4) adverse effects reported in placebo-controlled
trials in elderly primary insomnia patients; 5)
double-blind, placebo-controlled trials in adults and the
elderly as a function of treatment duration; 6)
double-blind, placebo-controlled trials of the treatment of
comorbid insomnia. Issues related to the application of
these data to clinical practice are discussed in the
text.},
Doi = {10.1016/j.smrv.2008.08.001},
Key = {fds281926}
}
@article{fds281924,
Author = {Omonuwa, TS and Goforth, HW and Preud'homme, X and Krystal,
AD},
Title = {The pharmacologic management of insomnia in patients with
HIV.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {5},
Number = {3},
Pages = {251-262},
Year = {2009},
Month = {June},
ISSN = {1550-9389},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19960648},
Abstract = {Insomnia is common in human immunodeficiency virus (HIV)
seropositive populations. Some studies have estimated as
many as 70% of HIV patients experience insomnia at some
point during their illness. Insomnia has been linked to
reduced quality of life as well as treatment non-adherence
in these patients. However, there has been very limited
research on the treatment of insomnia in this setting.
Lacking treatment trials, we carried out a review of the
available literature relevant to the pharmacologic treatment
of insomnia in HIV seropositive individuals in order to
provide guidance for the clinical management of this complex
population. A systematic MEDLINE search was performed using
as search terms each of the FDA approved or commonly
prescribed insomnia medications and "insomnia and HIV." In
addition, we reviewed the published literature on HIV
therapies and common comorbid conditions and their
interactions with insomnia therapies. We found 4 primary
factors affecting the pharmacotherapy of insomnia in
individuals with HIV: (1) medications used to treat HIV; (2)
antibiotics used to treat opportunistic infections; (3) the
HIV infection itself; and (4) conditions frequently
associated with HIV infection. The means by which these
factors affect the expected risk-benefit profile of insomnia
therapies is discussed, and recommendations are made for
choosing medications in patients encountered in clinical
practice.},
Key = {fds281924}
}
@article{fds281925,
Author = {Carney, CE and Ulmer, C and Edinger, JD and Krystal, AD and Knauss,
F},
Title = {Assessing depression symptoms in those with insomnia: an
examination of the beck depression inventory second edition
(BDI-II).},
Journal = {Journal of Psychiatric Research},
Volume = {43},
Number = {5},
Pages = {576-582},
Year = {2009},
Month = {February},
ISSN = {0022-3956},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18954876},
Abstract = {BACKGROUND: Due to concerns about overlapping symptomatology
between medical conditions and depression, the validity of
the beck depression inventory (BDI-II) has been assessed in
various medical populations. Although major depressive
disorder (MDD) and primary insomnia (PI) share some daytime
symptoms, the BDI-II has not been evaluated for use with
insomnia patients. METHOD: Participants (N=140) were
screened for the presence of insomnia using the Duke
structured clinical interview for sleep disorders (DSISD),
and evaluated for diagnosis of MDD using the structured
clinical interview for DSM-IV-TR (SCID). Participants' mean
BDI-II item responses were compared across two groups
[insomnia with or without MDD) using multivariate analysis
of variance (MANOVA), and the accuracy rates of suggested
clinical cutoffs for the BDI-II were evaluated using a
receiver operating characteristic (ROC) curve analysis.
RESULTS: The insomnia with depression group had
significantly higher scores on several items; however, the
groups did not differ on insomnia, fatigue, concentration
problems, irritability, libido, increased appetite, and
thoughts relating to suicide, self-criticism and punishment
items. The ROC curve analysis revealed moderate accuracy for
the BDI-II's identification of depression in those with
insomnia. The suggested BDI cutoff of >or=17 had 81%
sensitivity and 79% specificity. Use of the mild cutoff for
depression (>or=14) had high sensitivity (91%) but poor
specificity (66%). CONCLUSION: Several items on the BDI-II
might reflect sleep disturbance symptoms rather than
depression per se. The recommended BDI-II cutoffs in this
population have some support but a lower cutoff could result
in an overclassification of depression in insomnia patients,
a documented problem in the clinical literature.
Understanding which items discriminate insomnia patients
without depression may help address this nosological
issue.},
Doi = {10.1016/j.jpsychires.2008.09.002},
Key = {fds281925}
}
@article{fds281921,
Author = {Lisanby, SH and Husain, MM and Rosenquist, PB and Maixner, D and Gutierrez, R and Krystal, A and Gilmer, W and Marangell, LB and Aaronson, S and Daskalakis, ZJ and Canterbury, R and Richelson, E and Sackeim, HA and George, MS},
Title = {Daily left prefrontal repetitive transcranial magnetic
stimulation in the acute treatment of major depression:
clinical predictors of outcome in a multisite, randomized
controlled clinical trial.},
Journal = {Neuropsychopharmacology},
Volume = {34},
Number = {2},
Pages = {522-534},
Year = {2009},
Month = {January},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18704101},
Abstract = {Randomized controlled trials support the antidepressant
efficacy of transcranial magnetic stimulation (TMS);
however, there is individual variability in the magnitude of
response. Examination of response predictors has been
hampered by methodological limitations such as small sample
sizes and single-site study designs. Data from a multisite
sham-controlled trial of the antidepressant efficacy of TMS
provided an opportunity to examine predictors of acute
outcome. An open-label extension for patients who failed to
improve provided the opportunity for confirmatory analysis.
Treatment was administered to the left dorsolateral
prefrontal cortex at 10 pulses per second, 120% of motor
threshold, for a total of 3000 pulses per day. Change on the
Montgomery-Asberg Depression Rating Scale after 4 weeks was
the primary efficacy outcome. A total of 301 patients with
nonpsychotic unipolar major depression at 23 centers were
randomized to active or sham TMS. Univariate predictor
analyses showed that the degree of prior treatment
resistance in the current episode was a predictor of
positive treatment outcome in both the controlled study and
the open-label extension trial. In the randomized trial,
shorter duration of current episode was also associated with
a better outcome. In the open-label extension study, absence
of anxiety disorder comorbidity was associated with an
improved outcome, but duration of current episode was not.
The number of prior treatment failures was the strongest
predictor for positive response to acute treatment with TMS.
Shorter duration of current illness and lack of anxiety
comorbidity may also confer an increased likelihood of good
antidepressant response to TMS.},
Doi = {10.1038/npp.2008.118},
Key = {fds281921}
}
@article{fds311720,
Author = {Carney, CE and Edinger, JD and Wyatt, JK and Olsen, MK and Stechuchak,
KM and Chiang, A and Krystal, AD and Lineberger, MD and Means, MK and Radtke, RA},
Title = {SHOULD DSM-IV-TR PRIMARY INSOMNIA BE DIVIDED INTO SPECIFIC
SUBTYPES?},
Journal = {Sleep},
Volume = {32},
Pages = {A264-A265},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265542001158&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311720}
}
@article{fds311705,
Author = {Sutherland, ME and Edinger, JD and Carney, C and Preud'homme, X and Krystal, AD},
Title = {EFFECTS OF MANUAL ARTIFACT-REJECTION ON NON-REM SLEEP EEG
SPECTRAL ANALYSIS},
Journal = {Sleep},
Volume = {32},
Pages = {A374-A374},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265542001491&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311705}
}
@article{fds311715,
Author = {Edinger, JD and Wyatt, JK and Olsen, MK and Stechuchak, KM and Carney,
CE and Chiang, A and Krystal, AD and Lineberger, MD and Means, MK and Radtke, RA},
Title = {RELIABILITY AND VALIDITY OF THE DUKE STRUCTURED INTERVIEW
FOR SLEEP DISORDERS FOR INSOMNIA SCREENING},
Journal = {Sleep},
Volume = {32},
Pages = {A265-A265},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265542001159&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311715}
}
@article{fds311690,
Author = {Kane, JM and Krystal, AD and McKenzie, JE and Yang, R and Tiller, J and Youakim, JM},
Title = {SLEEP IN SCHIZOPHRENIA: A NIGHT- AND DAYTIME ACTIGRAPHY
STUDY IN PATIENTS WITH TREATED WITH ORAL RISPERIDONE,
OLANZAPINE OR PALIPERIDONE},
Journal = {Sleep},
Volume = {32},
Pages = {A355-A355},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265542001435&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311690}
}
@article{fds311716,
Author = {Edinger, JD and Wyatt, JK and Olsen, MK and Stechuchak, KM and Carney,
CE and Chiang, A and Krystal, AD and Lineberger, MD and Means, MK and Radtke, RA},
Title = {COMPARATIVE VALIDITY OF THE DSM-IV-TR AND ICSD-2 INSOMNIA
NOSOLOGIES: HOW MANY WAYS SHOULD WE SLICE THE INSOMNIA
PIE?},
Journal = {Sleep},
Volume = {32},
Pages = {A263-A263},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000265542001154&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311716}
}
@article{fds281922,
Author = {Preud'homme, XA and Lanquart, J-P and Krystal, AD and Bogaerts, P and Linkowski, P},
Title = {Modeling slow-wave activity dynamics: does an exponentially
dampened periodic function really fit a single night of
normal human sleep?},
Journal = {Clin Neurophysiol},
Volume = {119},
Number = {12},
Pages = {2753-2761},
Year = {2008},
Month = {December},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18986831},
Abstract = {OBJECTIVE: Slow-wave activity (SWA) is believed to be a
fundamental measure of sleep homeostasis and is frequently
characterized as an exponentially declining periodic
dynamical system. The objective of this study is to carry
out the first rigorous statistical test of this hypothesized
dynamical behavior. METHODS: Delta power (DP) was computed
for each epoch and artifacts were visually scored for 18
randomly selected nights from 18 healthy young men.
Non-linear least-squares (LS) combined with the simplex
algorithm were used to fit a 7-parameter confirmatory model
of DP separately for each individual night of data.
Individual night testing was employed because the model must
apply to individual night data to be of research or clinical
utility. RESULTS: Visually, results appeared satisfactory in
half of the cases, though the model was never statistically
verified. Validation using simulated data suggested that if
the exponentially declining sinusoidal model were correct,
satisfactory model fit would be expected on 17/18 nights.
CONCLUSIONS: An exponentially dampened periodic function
does not fit a single night of sleep amongst healthy young
men. Historically, averaging across nights was the primary
method used to develop such hypothesized model in order to
reduce variability in the data. Our validation with
simulated data established that this model does not fit
individual night data because the data in an individual
night do not conform to an exponentially dampened periodic
function and not because of variability. SIGNIFICANCE:
Further exploratory work is needed to determine how to
optimally model single night SWA data.},
Doi = {10.1016/j.clinph.2008.09.016},
Key = {fds281922}
}
@article{fds281920,
Author = {Krystal, AD and Edinger, JD},
Title = {Measuring sleep quality.},
Journal = {Sleep Med},
Volume = {9 Suppl 1},
Pages = {S10-S17},
Year = {2008},
Month = {September},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18929313},
Abstract = {Despite being used commonly in sleep medicine, the term
"sleep quality" has not been rigorously defined. The purpose
of this article is to consider objective measures of the
subjective "sleep quality" experience. In order to do so, it
was necessary to choose a definition of "sleep quality" as a
basis for discussion. We have chosen to employ the simple
Likert-style rating of (the previous night's) sleep quality,
commonly included as an item on sleep diaries, as the core
sleep quality indicator and focus of this article. The
potential objective measures discussed include
polysomnography, cyclic alternating pattern and actigraphy.
We review the strengths and weaknesses of these measures as
well as discuss challenges facing the development of an
objective correlate of "sleep quality" ratings, including
that such ratings may reflect non-sleep phenomena such as
mood or health status and the possibility that "sleep
quality" may reflect different aspects of sleep among
people. We also discuss new approaches intended to address
these challenges, including: (1) combining different types
of measures; (2) sub-grouping individuals based on clinical
or physiological characteristics and developing different
measures in these subgroups; and (3) sub-grouping based on
the association of potential measures and quality ratings
over nights.},
Doi = {10.1016/S1389-9457(08)70011-X},
Key = {fds281920}
}
@article{fds281923,
Author = {Krystal, AD},
Title = {Non-REM sleep EEG spectral analysis in insomnia},
Journal = {Psychiatric Annals},
Volume = {38},
Number = {9},
Pages = {615-620},
Year = {2008},
Month = {September},
ISSN = {0048-5713},
Abstract = {There is a need for objective measures of insomnia that can
be used in diagnosis and outcome assessment. Although PSG is
a valuable outcome assessment tool in a selected subset of
insomnia patients, we lack measures with diagnostic utility
and that can reflect outcome in the entire insomnia
population. Non-REM EEG spectral measures have the potential
to provide improved measures of the nature of the sleep
attained. They reflect the non-REM EEG signal frequency
content that is extracted primarily via an algorithm
referred to as the fast Fourier transform. The frequency
content of the EEG is reflected in the amplitude of a series
of frequency bands. Although sleep stages provide a
five-level categorical characterization of sleep, spectral
indices are continuous measures allowing a more fine-grained
characterization. Also, analysis of the pattern of spectral
indices over time can allow a dynamic analysis of sleep
physiology. The available studies employing spectral
analysis in insomnia suggest that there may be greater high
frequency and diminished low-frequency EEG activity in at
least a subset of insomnia patients. There is some data
suggesting that this is the case for those with insomnia who
tend to underestimate their sleep, compared with traditional
PSG indices of sleep quantity.10,20 This suggests the
possibility that spectral indices may reflect different
aspects of sleep than traditional indices and, therefore,
may be complementary measures with the potential to be
combined. Notably, there are few data on the use of spectral
indices as treatment outcome measures. Further studies
employing spectral indices to assess outcome are needed,
particularly where: 1) analyses of the relationship of
improvement in self-reported sleep and spectral indices are
carried out, and 2) where subjects are recruited who don't
meet traditional PSG entry criteria or who have alterations
in non-REM EEG frequency content. In addition, there is a
need to standardize methods of spectral analysis. It will
also be important to determine how/whether to combine
spectral indices with traditional PSG or other measures to
optimize diagnosis and outcome assessment.},
Key = {fds281923}
}
@article{fds281917,
Author = {Krystal, AD and Goforth, HW and Roth, T},
Title = {Effects of antipsychotic medications on sleep in
schizophrenia.},
Journal = {International Clinical Psychopharmacology},
Volume = {23},
Number = {3},
Pages = {150-160},
Year = {2008},
Month = {May},
ISSN = {0268-1315},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18408529},
Abstract = {Schizophrenia is often accompanied by sleep problems.
Evidence exists that these sleep difficulties have
significant effects on individuals with this disorder. The
mainstay of treatment for this condition is the
administration of medications that have effects on
neurotransmitter systems, which play an important role in
sleep-wake function, including histamine, acetylcholine,
serotonin, norepinephrine and dopamine. Little systematic
attention, however, has been paid to how the sleep effects
of these agents might play a role in the course of
treatment, function and quality of life of schizophrenia
patients. Schizophrenia medications can improve sleep
problems and reverse the sleep architectural derangements
that are common among patients with schizophrenia and,
therefore, have the potential to improve the quality of life
and functional capacity of the patient. Conversely, some
sleep-wake effects of these medications can impair patient
function and quality of life. In this study, we review the
effects of schizophrenia medications and discuss their
relevance to optimizing the clinical treatment of people
with schizophrenia with regard to sleep-wake
function.},
Doi = {10.1097/YIC.0b013e3282f39703},
Key = {fds281917}
}
@article{fds281918,
Author = {Pollack, M and Kinrys, G and Krystal, A and McCall, WV and Roth, T and Schaefer, K and Rubens, R and Roach, J and Huang, H and Krishnan,
R},
Title = {Eszopiclone coadministered with escitalopram in patients
with insomnia and comorbid generalized anxiety
disorder.},
Journal = {Arch Gen Psychiatry},
Volume = {65},
Number = {5},
Pages = {551-562},
Year = {2008},
Month = {May},
ISSN = {0003-990X},
url = {http://dx.doi.org/10.1001/archpsyc.65.5.551},
Abstract = {CONTEXT: Insomnia and generalized anxiety disorder (GAD) are
prevalent disorders that may coexist. OBJECTIVE: To
determine the efficacy of eszopiclone combined with
escitalopram oxalate in treating insomnia comorbid with GAD.
DESIGN: Double-blind, randomized, placebo-controlled,
parallel-group, add-on therapy 10-week study. SETTING:
Multicenter outpatient study from July 2005 to April 2006.
PATIENTS: Adults aged 18 to 64 years meeting DSM-IV-TR
criteria for GAD and insomnia. INTERVENTIONS: Patients
received 10 mg of escitalopram oxolate for 10 weeks and were
randomized to also receive either 3 mg of eszopiclone (n =
294) or placebo (n = 301) nightly for 8 weeks. For the last
2 weeks, eszopiclone was replaced with a single-blind
placebo. MAIN OUTCOME MEASURES: Sleep, daytime functioning,
psychiatric measures, and adverse events. RESULTS: Compared
with treatment with placebo and escitalopram, treatment with
eszopiclone and escitalopram resulted in significantly
improved sleep and daytime functioning (P < .05), with no
evidence of tolerance. Patients taking eszopiclone and
escitalopram had greater improvements in total Hamilton
Anxiety Scale (HAM-A) scores at each week (P < .05) and at
weeks 4 through 10 with the insomnia item removed. Clinical
Global Impressions (CGI) of Improvement scores were improved
with eszopiclone and escitalopram at every point (P < .02),
while CGI of Severity of Illness scores were not
significantly different after week 1. The HAM-A response
(63% vs 49%, respectively, P = .001) and remission (42% vs
36%, respectively, P = .09) rates at week 8 were higher in
patients treated with eszopiclone and escitalopram than
those treated with placebo and escitalopram, and median time
to onset of anxiolytic response was significantly reduced (P
< or = .05). After eszopiclone discontinuation, there was no
evidence of rebound insomnia, and while treatment
differences in anxiety measures were maintained, differences
in sleep outcomes were not. Overall adverse event rates were
77.6% with cotherapy and 67.9% with monotherapy. The most
common adverse events with cotherapy were unpleasant taste,
headache, dry mouth, and somnolence. CONCLUSIONS:
Coadministration of eszopiclone and escitalopram was well
tolerated and associated with significantly improved sleep,
daytime functioning, anxiety, and mood in patients with
insomnia and GAD. TRIAL REGISTRATION: clinicaltrials.gov
Identifier: NCT00235508.},
Doi = {10.1001/archpsyc.65.5.551},
Key = {fds281918}
}
@article{fds281919,
Author = {Edinger, JD and Means, MK and Carney, CE and Krystal,
AD},
Title = {Psychomotor performance deficits and their relation to prior
nights' sleep among individuals with primary
insomnia.},
Journal = {Sleep},
Volume = {31},
Number = {5},
Pages = {599-607},
Year = {2008},
Month = {May},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18517030},
Abstract = {OBJECTIVE: To examine psychomotor (reaction time)
performance deficits and their relation to subjective and
objective sleep measures among individuals with primary
insomnia (PI). DESIGN AND SETTING: This study was conducted
at affiliated VA and academic medical centers using a
matched-groups, cross-sectional research design.
PARTICIPANTS: Seventy-nine (43 women) individuals with PI
(MAge = 50.0 +/- 17.1 y) and 84 (41 women) well-screened
normal sleepers (MAge = 48.6 +/- 16.8 y). METHODS AND
MEASURES: Participants underwent 3 nights of polysomnography
(PSG) followed by daytime testing with a 4-trial multiple
sleep latency test (MSLT). Before each MSLT nap, they rated
their sleepiness and completed a performance battery that
included simple reaction time (SRT), continuous performance
(CPT), and 4 switching attention (SAT) tests. Performance
measures included the mean response latency and the standard
deviation of each subject's within-test response latencies.
RESULTS: PI sufferers reported greater (P = 0.001) daytime
sleepiness, but were significantly (P = 0.02), more alert
than normal sleepers on the MSLT. Multivariate analyses
showed the PI group had significantly longer response
latencies and greater response variability across many of
the subtests than did the controls. Regression analyses
showed that both PSG- and diary-based sleep measures
contributed to the prediction of daytime performance
indices, although objective wake time after sleep onset
appeared the best single predictor of the daytime measures.
CONCLUSIONS: Results confirm that PI sufferers do show
relative psychomotor performance deficits when responding to
challenging reaction time tasks, and these deficits appear
related to both objective and subjective sleep deficits.
Findings support PI patients' diurnal complaints and suggest
the usefulness of complex reaction time tasks for assessing
them.},
Doi = {10.1093/sleep/31.5.599},
Key = {fds281919}
}
@article{fds281957,
Author = {Krystal, JH and Carter, CS and Geschwind, D and Manji, HK and March, JS and Nestler, EJ and Zubieta, J-K and Charney, DS and Goldman, D and Gur, RE and Lieberman, JA and Roy-Byrne, P and Rubinow, DR and Anderson, SA and Barondes, S and Berman, KF and Blair, J and Braff, DL and Brown, ES and Calabrese, JR and Carlezon, WA and Cook, EH and Davidson, RJ and Davis,
M and Desimone, R and Drevets, WC and Duman, RS and Essock, SM and Faraone,
SV and Freedman, R and Friston, KJ and Gelernter, J and Geller, B and Gill,
M and Gould, E and Grace, AA and Grillon, C and Gueorguieva, R and Hariri,
AR and Innis, RB and Jones, EG and Kleinman, JE and Koob, GF and Krystal,
AD and Leibenluft, E and Levinson, DF and Levitt, PR and Lewis, DA and Liberzon, I and Lipska, BK and Marder, SR and Markou, A and Mason, GF and McDougle, CJ and McEwen, BS and McMahon, FJ and Meaney, MJ and Meltzer,
HY and Merikangas, KR and Meyer-Lindenberg, A and Mirnics, K and Monteggia, LM and Neumeister, A and O'Brien, CP and Owen, MJ and Pine,
DS and Rapoport, JL and Rauch, SL and Robbins, TW and Rosenbaum, JF and Rosenberg, DR and Ross, CA and Rush, AJ and Sackeim, HA and Sanacora, G and Schatzberg, AF and Shaham, Y and Siever, LJ and Sunderland, T and Tecott, LH and Thase, ME and Todd, RD and Weissman, MM and Yehuda, R and Yoshikawa, T and Young, EA and McCandless, R},
Title = {It is time to take a stand for medical research and against
terrorism targeting medical scientists.},
Journal = {Biol Psychiatry},
Volume = {63},
Number = {8},
Pages = {725-727},
Year = {2008},
Month = {April},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18371494},
Doi = {10.1016/j.biopsych.2008.03.005},
Key = {fds281957}
}
@article{fds281961,
Author = {Chiang, A and Krystal, A},
Title = {Report of two cases where sleep related eating behavior
occurred with the extended-release formulation but not the
immediate-release formulation of a sedative-hypnotic
agent.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {4},
Number = {2},
Pages = {155-156},
Year = {2008},
Month = {April},
ISSN = {1550-9389},
Abstract = {We report two cases in which amnestic sleep related eating
disorder (SRED) occurred with extended-release zolpidem but
not with the immediate-release formulation. These cases
illustrate how even relatively small differences such as
formulation can affect the likelihood of experiencing such
events.},
Key = {fds281961}
}
@article{fds281915,
Author = {Krystal, AD and Erman, M and Zammit, GK and Soubrane, C and Roth, T and ZOLONG Study Group},
Title = {Long-term efficacy and safety of zolpidem extended-release
12.5 mg, administered 3 to 7 nights per week for 24 weeks,
in patients with chronic primary insomnia: a 6-month,
randomized, double-blind, placebo-controlled,
parallel-group, multicenter study.},
Journal = {Sleep},
Volume = {31},
Number = {1},
Pages = {79-90},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18220081},
Abstract = {STUDY OBJECTIVES: To evaluate long-term efficacy and safety
of zolpidem extended-release 3 to 7 nights/week for chronic
primary insomnia. DESIGN: Multicenter, 25-week, phase IIIb,
randomized, double-blind, placebo-controlled,
parallel-group. SETTING: Outpatient; visits every 4 weeks.
PATIENTS: Aged 18 to 64 years; DSM-IV criteria for chronic
primary insomnia; > or =3 months of difficulty initiating or
maintaining sleep or experiencing nonrestorative sleep.
INTERVENTIONS: Single-dose zolpidem extended-release 12.5 mg
(n = 669) or placebo (n = 349), self-administered from a
minimum of 3 nights/week to a maximum of 7 nights/week.
MEASUREMENTS AND RESULTS: Patient's Global Impression (PGI)
and Clinical Global Impression-Improvement (CGI-I) were
assessed every 4 weeks up to week 24. Patient Morning
Questionnaire (PMQ), recorded daily, assessed subjective
sleep measures-sleep onset latency (SOL), total sleep time
(TST), number of awakenings (NAW), wake time after sleep
onset (WASO), and quality of sleep (QOS)-and next-day
functioning. At week 12, PGI, Item 1 (aid to sleep), the
primary endpoint, was scored as favorable (i.e., "helped me
sleep") by 89.8% of zolpidem patients vs. 51.4% of placebo
patients (P < 0.0001, based on rank score) and at week 24 by
92.3% of zolpidem extended-release patients vs. 59.7% of
placebo patients. Zolpidem extended-release also was
statistically significantly superior to placebo at every
time point for PGI (Items 1-4) and CGI-I (P < 0.0001, rank
score), TST, WASO, QOS (P < 0.0001), and SOL (P < or =
0.0014); NAW (Months 2-6; P < 0.0001). Sustained improvement
(P < 0.0001, all time points) was observed in morning
sleepiness and ability to concentrate (P = 0.0014, month 6)
with zolpidem extended-release compared with placebo. Most
frequent adverse events for zolpidem extended-release were
headache, anxiety and somnolence. No rebound effect was
observed during the first 3 nights of discontinuation.
CONCLUSIONS: These findings establish the efficacy of 3 to 7
nights per week dosing of zolpidem extended-release 12.5 mg
for up to 6 months. Treatment provided sustained and
significant improvements in sleep onset and maintenance and
also improved next-day concentration and morning
sleepiness.},
Doi = {10.1093/sleep/31.1.79},
Key = {fds281915}
}
@article{fds281916,
Author = {Krystal, AD and Thakur, M and Roth, T},
Title = {Sleep disturbance in psychiatric disorders: effects on
function and quality of life in mood disorders, alcoholism,
and schizophrenia.},
Journal = {Ann Clin Psychiatry},
Volume = {20},
Number = {1},
Pages = {39-46},
Year = {2008},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18297585},
Abstract = {INTRODUCTION: While the precise role of sleep in maintaining
optimal health and function remains unknown, it is clear
that disturbances of sleep have a profound impact on the
lives of affected individuals. In psychiatric disorders, not
only is there a relationship between sleep disturbances and
impaired function, problems with sleep also appear to affect
the course of the disorder. METHODS: We carried out a
literature review of sleep studies in mood disorders,
alcoholism and schizophrenia to determine how associated
alterations in sleep architecture and disturbances of sleep
are related to patient function and quality of life, and the
course of these disorders. RESULTS: The literature speaks to
the need to address sleep problems in the overall management
of mood disorders, alcoholism and schizophrenia. The support
for this viewpoint is best established for mood disorders.
There is also relatively strong support for treatment in
alcoholism. Schizophrenia, however, has received scant
attention and the literature suggests a need for more
studies in this area. CONCLUSIONS: Further research is
needed into the treatment of co-morbid insomnia and
psychiatric disorders. Successful therapy is more likely to
be achieved if the sleep difficulty and co-morbid disorder
are simultaneously targeted for treatment.},
Doi = {10.1080/10401230701844661},
Key = {fds281916}
}
@article{fds281914,
Author = {Walsh, JK and Krystal, AD and Amato, DA and Rubens, R and Caron, J and Wessel, TC and Schaefer, K and Roach, J and Wallenstein, G and Roth,
T},
Title = {Nightly treatment of primary insomnia with eszopiclone for
six months: effect on sleep, quality of life, and work
limitations.},
Journal = {Sleep},
Volume = {30},
Number = {8},
Pages = {959-968},
Year = {2007},
Month = {August},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17702264},
Abstract = {STUDY OBJECTIVES: To evaluate 6 months' eszopiclone
treatment upon patient-reported sleep, fatigue and
sleepiness, insomnia severity, quality of life, and work
limitations. DESIGN: Randomized, double blind, controlled
clinical trial. SETTING: 54 research sites in the U.S.
PATIENTS: 830 primary insomnia patients who reported mean
nightly total sleep time (TST) < or = 6.5 hours/night and/or
mean nightly sleep latency (SL) >30 min. INTERVENTION:
Eszopiclone 3 mg or matching placebo. MEASUREMENTS:
Patient-reported sleep measures, Insomnia Severity Index,
Medical Outcomes Study Short-Form Health Survey (SF-36),
Work Limitations Questionnaire, and other assessments
measured during baseline, treatment Months 1-6, and 2 weeks
following discontinuation of treatment. RESULTS:
Patient-reported sleep and daytime function were improved
more with eszopiclone than with placebo at all months (P
<0.001). Eszopiclone reduced Insomnia Severity Index scores
to below clinically meaningful levels for 50% of patients
(vs 19% with placebo; P <0.05) at Month 6. SF-36 domains of
Physical Functioning, Vitality, and Social Functioning were
improved with eszopiclone vs placebo for the Month 1-6
average (P < 0.05). Similarly, improvements were observed
for all domains of the Work Limitations Questionnaire with
eszopiclone vs placebo for the Month 1-6 average (P <0.05).
CONCLUSIONS: This is the first placebo-controlled
investigation to demonstrate that long-term nightly
pharmacologic treatment of primary insomnia with any
hypnotic enhanced quality of life, reduced work limitations,
and reduced global insomnia severity, in addition to
improving patient-reported sleep variables.},
Doi = {10.1093/sleep/30.8.959},
Key = {fds281914}
}
@article{fds281911,
Author = {Roth, T and Krystal, AD and Lieberman, JA},
Title = {Long-term issues in the treatment of sleep
disorders},
Journal = {Primary Psychiatry},
Volume = {14},
Number = {7},
Pages = {1-14},
Year = {2007},
Month = {July},
ISSN = {1082-6319},
Abstract = {Insomnia is a disorder characterized by chronic sleep
disturbance associated with daytime disability or distress,
such as memory impairment and fatigue, that occurs despite
adequate opportunity for sleep. Insomnia may present as
difficulty falling/staying asleep or as sleep that is
nonrestorative. Studies show a strong correlation between
insomnia and impaired quality of life. Pain conditions and
depression are commonly associated with insomnia, either as
secondary or comorbid conditions. In addition, a greater
incidence of anxiety, alcohol and drug dependence, and
cardiovascular disease is found in people with insomnia.
Data indicate insomnia results from over-engaged arousal
systems. Insomnia patients experience increased metabolic
rate, body temperature, and heart rate, and elevated levels
of norepinephrine and catecholamines. Pharmacologic options
for the treatment of insomnia include benzodiazepine
hypnotics, a selective melatonin receptor agonist, and
sedating antidepressants. However, insomnia may be best
treated with cognitive-behavioral therapy and instruction in
good sleep hygiene, either alone or in concert with
pharmacologic agents. Studies on the effects of insomnia
treatment use variable methodologies or do not publish
negative results, and there are currently no studies of
treatment focusing on morbidity. Further research is
necessary to better understand the effects of insomnia
therapies on medical and psychiatric disorders. In this
Clinical Information Supplement, Thomas Roth, PhD, describes
the nature of insomnia and its pathophysiology. Next, Andrew
D. Krystal, MD, MS, reviews morbidities associated with
insomnia. Finally, Joseph A. Lieberman III, MD, MPH,
provides an overview of therapeutics utilized in patients
with insomnia, including behavioral therapies and
pharmacologic options. Copyright ©2007 MBL Communications,
Inc. All rights reserved, including the right of
reproduction, in whole or in part, in any
form.},
Key = {fds281911}
}
@article{fds281913,
Author = {Roth, T and Krystal, AD and Lieberman, JA},
Title = {Long-term issues in the treatment of sleep
disorders.},
Journal = {Cns Spectrums},
Volume = {12},
Number = {7 Suppl 10},
Pages = {1-14},
Year = {2007},
Month = {July},
ISSN = {1092-8529},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17603408},
Abstract = {Insomnia is a disorder characterized by chronic sleep
disturbance associated with daytime disability or distress,
such as memory impairment and fatigue, that occurs despite
adequate opportunity for sleep. Insomnia may present as
difficulty falling/staying asleep or as sleep that is
nonrestorative. Studies show a strong correlation between
insomnia and impaired quality of life. Pain conditions and
depression are commonly associated with insomnia, either as
secondary or comorbid conditions. In addition, a greater
incidence of anxiety, alcohol and drug dependence, and
cardiovascular disease is found in people with insomnia.
Data indicate insomnia results from over-engaged arousal
systems. Insomnia patients experience increased metabolic
rate, body temperature, and heart rate, and elevated levels
of norepinephrine and catecholamines. Pharmacologic options
for the treatment of insomnia include benzodiazepine
hypnotics, a selective melatonin receptor agonist, and
sedating antidepressants. However, insomnia may be best
treated with cognitive-behavioral therapy and instruction in
good sleep hygiene, either alone or in concert with
pharmacologic agents. Studies on the effects of insomnia
treatment use variable methodologies or do not publish
negative results, and there are currently no studies of
treatment focusing on morbidity. Further research is
necessary to better understand the effects of insomnia
therapies on medical and psychiatric disorders. In this
Clinical Information Supplement, Thomas Roth, PhD, describes
the nature of insomnia and its pathophysiology. Next, Andrew
D. Krystal, MD, MS, reviews morbidities associated with
insomnia. Finally, Joseph A. Lieberman III, MD, MPH,
provides an overview of therapeutics utilized in patients
with insomnia, including behavioral therapies and
pharmacologic options.},
Key = {fds281913}
}
@article{fds281912,
Author = {Lim, L and Krystal, A},
Title = {Psychotic disorder in a patient with central and
extrapontine myelinolysis.},
Journal = {Psychiatry and Clinical Neurosciences},
Volume = {61},
Number = {3},
Pages = {320-322},
Year = {2007},
Month = {June},
ISSN = {1323-1316},
url = {http://dx.doi.org/10.1111/j.1440-1819.2007.01648.x},
Abstract = {Central pontine and extrapontine myelinolysis (CPEM) are
rare conditions usually associated with rapid correction of
hyponatremia. Neurologic complications are the usual
sequelae although neuropsychiatric features are rare.
Described herein are unusual psychotic symptoms following
CPEM and discussion of the likely pathogenesis and
implications for treatment.},
Doi = {10.1111/j.1440-1819.2007.01648.x},
Key = {fds281912}
}
@article{fds281964,
Author = {Brummett, BH and Krystal, AD and Siegler, IC and Kuhn, C and Surwit, RS and Züchner, S and Ashley-Koch, A and Barefoot, JC and Williams,
RB},
Title = {Associations of a regulatory polymorphism of monoamine
oxidase-A gene promoter (MAOA-uVNTR) with symptoms of
depression and sleep quality.},
Journal = {Psychosom Med},
Volume = {69},
Number = {5},
Pages = {396-401},
Year = {2007},
Month = {June},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17585061},
Abstract = {OBJECTIVE: To examine the relationships among the variable
number of tandem repeats in the monoamine oxidase-A linked
polymorphic region allelic variation (MAOA-uVNTR) and the
symptoms of depression and sleep quality. The monoamine
oxidase-A (MAOA) gene, which plays a vital role in
degradation of neurotransmitters such as serotonin,
norepinephrine, and dopamine, contains a polymorphism in its
promoter region (MAOA-uVNTR) that affects transcriptional
efficiency. MAOA-uVNTR genotype has been associated with
both psychological and physical measures. METHODS: The
sample consisted of 74 males enrolled in a case/control
study of caregivers for relatives with dementia. Age- and
race-adjusted linear regression models were used to examine
the association between low versus high MAOA-uVNTR activity
alleles, symptoms of depression (Center for Epidemiological
Studies of Depression), and sleep quality ratings
(Pittsburgh Sleep Quality Index). RESULTS: MAOA-uVNTR
alleles associated with less transcriptional activity were
related to increased symptoms of depression (p < .04;
Cohen's d = 0.52) and poorer sleep quality (p < .04; Cohen's
d = 0.31). CONCLUSIONS: Individuals with less active
MAOA-uVNTR alleles may be at increased risk for depressive
symptoms and poor sleep.},
Doi = {10.1097/PSY.0b013e31806d040b},
Key = {fds281964}
}
@article{fds281910,
Author = {Krystal, AD and Thase, ME and Tucker, VL and Goodale,
EP},
Title = {Bupropion HCL and sleep in patients with
depression},
Journal = {Current Psychiatry Reviews},
Volume = {3},
Number = {2},
Pages = {123-128},
Publisher = {Bentham Science Publishers Ltd.},
Year = {2007},
Month = {May},
ISSN = {1573-4005},
url = {http://dx.doi.org/10.2174/157340007780599096},
Abstract = {Objectives: Depressed patients often have insomnia, daytime
sleepiness, and/or changes in sleep architecture. These
sleep/wake changes are associated with diminished quality of
life, impaired function, diminished treatment response and
greater risk of relapse. Antidepressants may cause,
exacerbate, or ameliorate these sleep/wake alterations. The
sleep/wake effects of bupropion, a norepinephrine/ dopamine
re-uptake inhibitor (NDRI), are relatively less well
established. We carried out this literature review in order
to characterize the sleep/wake effects of bupropion, provide
an understanding of the antidepressant mechanisms involved
and discuss implications for clinical practice. Methods:
Manuscripts were identified using PubMed. In addition,
reports were selected from references in the original search
and reports concerning bupropion extended-release were
provided by the manufacturer. Results: Bupropion was not
associated with daytime sedation. Sleep disturbance occurs
at a low rate, comparable to other modern reuptake
inhibitors. Unlike other antidepressants, bupropion does not
suppress REM sleep nor increase the risk of periodic leg
movement disorder. Conclusion: Bupropion has a unique
sleep/wake profile, which may be particularly well-suited
for treatment of individuals suffering from depression
accompanied by significant fatigue/sleepiness. A lack of REM
suppression, which likely reflects bupropion's NDRI
mechanism of action, is also distinctive and does not affect
antidepressant efficacy. © 2007 Bentham Science Publishers
Ltd.},
Doi = {10.2174/157340007780599096},
Key = {fds281910}
}
@article{fds281909,
Author = {Krystal, AD and Davidson, JRT},
Title = {The use of prazosin for the treatment of trauma nightmares
and sleep disturbance in combat veterans with post-traumatic
stress disorder.},
Journal = {Biological Psychiatry},
Volume = {61},
Number = {8},
Pages = {925-927},
Year = {2007},
Month = {April},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17397667},
Doi = {10.1016/j.biopsych.2007.02.020},
Key = {fds281909}
}
@article{fds363102,
Author = {Montgomery, S and Kinrys, G and Krystal, A and McCall, WV and Roth, T and Rubens, R and Schaefer, K and Roach, J and Huang, H and Krishnan, R and Pollack, M},
Title = {Evaluation of eszopiclone and escitalopram oxalate
co-therapy in patients with generalized anxiety disorder and
insomnia},
Journal = {European Psychiatry},
Volume = {22},
Pages = {S238-S239},
Publisher = {Cambridge University Press (CUP)},
Year = {2007},
Month = {March},
url = {http://dx.doi.org/10.1016/j.eurpsy.2007.01.798},
Doi = {10.1016/j.eurpsy.2007.01.798},
Key = {fds363102}
}
@article{fds281907,
Author = {Krystal, A and Fava, M and Rubens, R and Wessel, T and Caron, J and Wilson,
P and Roth, T and McCall, WV},
Title = {Evaluation of eszopiclone discontinuation after cotherapy
with fluoxetine for insomnia with coexisting
depression.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {3},
Number = {1},
Pages = {48-55},
Year = {2007},
Month = {February},
ISSN = {1550-9389},
Abstract = {BACKGROUND: Insomnia and major depressive disorder (MDD) may
coexist. This study evaluated hypnotic discontinuation
effects following an 8-week placebo-controlled study of
eszopiclone/fluoxetine cotherapy in patients with insomnia
and comorbid MDD. METHODS: Patients meeting DSM-IV criteria
for MDD and insomnia received fluoxetine each morning for 8
weeks and were randomized to concomitant treatment with
nightly eszopiclone 3 mg (cotherapy) or placebo
(monotherapy). Thereafter, patients received 2 weeks of
continued fluoxetine plus single-blind placebo. RESULTS:
Incidence rates of central nervous system (CNS) and
potentially CNS-related adverse events (AEs) during the
run-out period were similar between treatment groups (8.8%
with monotherapy vs 9.8% with cotherapy), and there was no
evidence of benzodiazepine withdrawal AEs.
Physician-assessed Clinical Global Impression improvements
in depressive symptoms were maintained after eszopiclone
discontinuation. Improvements in 17-item Hamilton-Depression
Rating Scale (HAMD-17) scores with cotherapy versus
monotherapy seen at Week 8 (p = .0004) were maintained at
Week 10 (p < .0001) and significantly higher depression
response and remission rates were observed after cotherapy
at Week 10 (p < .02). Patients discontinued from eszopiclone
maintained improvements in SL (sleep latency), WASO (wake
after sleep onset), and TST (total sleep time) during the 2
weeks following discontinuation (p < .05). CONCLUSIONS: In
this study, eszopiclone discontinuation did not result in
significant CNS or benzodiazepine withdrawal AEs, rebound
insomnia, or rebound depression; and improvements in sleep
and depressive symptoms were maintained.},
Key = {fds281907}
}
@article{fds281908,
Author = {Krystal, AD},
Title = {Treating the health, quality of life, and functional
impairments in insomnia.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {3},
Number = {1},
Pages = {63-72},
Year = {2007},
Month = {February},
ISSN = {1550-9389},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17557457},
Abstract = {STUDY OBJECTIVES: Impairments in health, function, and
quality of life (QOL) are a central feature of insomnia, yet
insomnia treatment is targeted solely to improving problems
falling and staying asleep. It is not even known if the
nonsleep deficits improve with current treatment. We
hypothesized that therapy that improves sleep also improves
these nonsleep difficulties and carried out this review to
test that hypothesis. METHODS: A literature search
identified the health, function, and QOL deficits of
insomnia patients. A second search determined the effect of
insomnia treatments on those problems, capturing randomized
controlled treatment trials in insomnia patients that
included relevant measures. RESULTS: Insomnia patients
report a variety of symptoms, including daytime sleepiness,
fatigue, cognitive impairment, symptoms of depression,
anxiety, health decrements, and impairment in social and
occupational function. However, the reported deficits are
generally not paralleled by objective evidence of
impairment. Nineteen treatment studies reported measures
related to these deficits. At least one treatment
(eszopiclone [5 studies], zopiclone [2 studies], progressive
muscle relaxation [2], zolpidem [2], multi-component
cognitive-behavioral therapy [1], doxepin [1], valerian/hops
[1], and stimulus control [1]) led to a significant
improvement compared with placebo in at least one of these
measures in 14/20 studies. CONCLUSIONS: Treatment can
improve the perceived health, function, and QOL of insomnia
patients. This potential improvement signals the need to
shift the attention of research and clinical practice to
include aspects other than sleep difficulties and move
towards defining successful therapy as not only improving
sleep but also eliminating deficits in health, function, and
QOL.},
Key = {fds281908}
}
@article{fds281906,
Author = {Carney, CE and Segal, ZV and Edinger, JD and Krystal,
AD},
Title = {A comparison of rates of residual insomnia symptoms
following pharmacotherapy or cognitive-behavioral therapy
for major depressive disorder.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {68},
Number = {2},
Pages = {254-260},
Year = {2007},
Month = {February},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17335324},
Abstract = {OBJECTIVE: A number of pharmacologic studies have documented
that insomnia is among the most commonly reported residual
symptoms after remission from depression. Residual symptoms
after remission are particularly relevant because these
symptoms confer greater risk for subsequent depression. This
study was the first to date to examine residual insomnia
after cognitive-behavioral therapy (CBT) for depression and
to compare CBT with pharmacotherapy for depression on
residual insomnia rates. METHOD: This naturalistic study
examined rates of posttreatment insomnia complaints in
patients (N = 94) who had been diagnosed with major
depressive disorder (MDD), according to DSM-IV criteria, and
who remitted from MDD after completing at least 20 weeks of
either CBT or pharmacotherapy at an outpatient clinic
specializing in mood disorders. Participants were randomly
assigned to the treatment conditions, but only the data from
those who completed treatment and remitted were analyzed.
Primary outcome measure was the 17-item Hamilton Rating
Scale for Depression. Data were collected from October 1,
1999, to September 23, 2003. Groups were compared using a
chi(2) for nominal data. RESULTS: The rate of posttreatment
insomnia was 22% for sleep-onset insomnia, 26% for
sleep-maintenance insomnia, and 17% for early morning
awakenings, and the rates did not statistically differ
across the 2 treatment groups. CONCLUSION: Although CBT and
pharmacotherapy effectively addressed depression in these
patients and addressed insomnia symptoms for many, there
were a number of patients with residual insomnia. Whereas
there appears to be no difference between CBT and
pharmacotherapy with regard to rates of residual insomnia,
the rates of such insomnia remaining after these treatments
suggest that adjunctive sleep treatment to specifically
address insomnia may be necessary for some MDD
patients.},
Doi = {10.4088/jcp.v68n0211},
Key = {fds281906}
}
@article{fds323882,
Author = {Krystal, AD},
Title = {The Morbidity of Insomnia},
Journal = {Cns Spectrums},
Volume = {12},
Number = {S10},
Pages = {6-8},
Publisher = {Cambridge University Press (CUP)},
Year = {2007},
Month = {January},
url = {http://dx.doi.org/10.1017/S1092852900026110},
Abstract = {Insomnia is a disorder characterized by chronic sleep
disturbance associated with daytime disability or distress,
such as memory impairment and fatigue, that occurs despite
adequate opportunity for sleep. Insomnia may present as
difficulty falling/staying asleep or as sleep that is
nonrestorative. Studies show a strong correlation between
insomnia and impaired quality of life. Pain conditions and
depression are commonly associated with insomnia, either as
secondary or comorbid conditions. In addition, a greater
incidence of anxiety, alcohol and drug dependence, and
cardiovascular disease is found in people with insomnia.
Data indicate insomnia results from over-engaged arousal
systems. Insomnia patients experience increased metabolic
rate, body temperature, and heart rate, and elevated levels
of norepinephrine and catecholamines. Pharmacologic options
for the treatment of insomnia include benzodiazepine
hypnotics, a selective melatonin receptor agonist, and
sedating antidepressants. However, insomnia may be best
treated with cognitive-behavioral therapy and instruction in
good sleep hygiene, either alone or in concert with
pharmacologic agents. Studies on the effects of insomnia
treatment use variable methodologies or do not publish
negative results, and there are currently no studies of
treatment focusing on morbidity. Further research is
necessary to better understand the effects of insomnia
therapies on medical and psychiatric disorders. In this
Clinical Information Supplement, Thomas Roth, PhD, describes
the nature of insomnia and its pathophysiology. Next, Andrew
D. Krystal, MD, MS, reviews morbidities associated with
insomnia. Finally, Joseph A. Lieberman III, MD, MPH,
provides an overview of therapeutics utilized in patients
with insomnia, including behavioral therapies and
pharmacologic options. © 2007, Cambridge University Press.
All rights reserved.},
Doi = {10.1017/S1092852900026110},
Key = {fds323882}
}
@article{fds281965,
Author = {Brummett, BH and Krystal, AD and Ashley-Koch, A and Kuhn, CM and Züchner, S and Siegler, IC and Barefoot, JC and Ballard, EL and Gwyther, LP and Williams, RB},
Title = {Sleep quality varies as a function of 5-HTTLPR genotype and
stress.},
Journal = {Psychosom Med},
Volume = {69},
Number = {7},
Pages = {621-624},
Year = {2007},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17766685},
Abstract = {OBJECTIVE: To test the hypothesis that allelic variation in
5HTT gene-linked polymorphic region (5-HTTLPR) genotype was
associated with sleep quality (Pittsburgh Sleep Quality
Index, PSQI) as a main effect and as moderated by the
chronic stress of caregiving. Serotonin (5HT) is involved in
sleep regulation and the 5HT transporter (5HTT) regulates
5HT function. A common 44-base pair deletion (s allele)
polymorphism in the 5-HTTLPR is associated with reduced 5HTT
transcription efficiency and 5HT uptake in vitro. METHODS:
Subjects were 142 adult primary caregivers for a spouse or
parent with dementia and 146 noncaregiver controls. Subjects
underwent genotyping and completed the PSQI. RESULTS:
Variation in 5-HTTLPR genotype was not related to sleep
quality as a main effect (p > .36). However, there was a
caregiver X 5-HTTLPR interaction (p < .009), such that the s
allele was associated with poorer sleep quality in
caregivers as compared with controls. CONCLUSIONS: Findings
suggest that the s allele may moderate sleep disturbance in
response to chronic stress.},
Doi = {10.1097/PSY.0b013e31814b8de6},
Key = {fds281965}
}
@article{fds281905,
Author = {Krystal, AD},
Title = {Sleep and psychiatric disorders: future directions.},
Journal = {The Psychiatric Clinics of North America},
Volume = {29},
Number = {4},
Pages = {1115-1130},
Year = {2006},
Month = {December},
ISSN = {0193-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17118285},
Abstract = {Understanding of the relationship between co-occurring sleep
and psychiatric disorders has undergone a radical change.
The longstanding perspective that sleep problems invariably
are a symptom of a psychiatric disorder is giving way to
understanding that complex bidirectional relationships may
exist. This change has opened doors to new directions in
research and led to changes in guidelines for clinical
practice. This article discusses promising future directions
for building on this foundation, including developing lines
of research currently underway, studying mechanisms that
underlie the relationships between sleep and psychiatric
disorders; and developing treatment strategies that target
these mechanisms to lead to better treatment of sleep
disorders and psychiatric disorders.},
Doi = {10.1016/j.psc.2006.09.001},
Key = {fds281905}
}
@article{fds281904,
Author = {Zammit, GK and Corser, B and Doghramji, K and Fry, JM and James, S and Krystal, A and Mangano, RM},
Title = {Sleep and residual sedation after administration of
zaleplon, zolpidem, and placebo during experimental
middle-of-the-night awakening.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {2},
Number = {4},
Pages = {417-423},
Year = {2006},
Month = {October},
ISSN = {1550-9389},
Abstract = {STUDY OBJECTIVES: To assess the efficacy of zaleplon 10 mg
and zolpidem 10 mg administered during experimental
middle-of-the-night awakenings in patients with
sleep-maintenance insomnia using objective polysomnographic
measures and to assess daytime residual sedation 4 to 7
hours after dosing using sleep-latency testing. DESIGN: A
randomized, double-blind, placebo-controlled, 3-period,
crossover design was used to study 37 adults with insomnia
who received treatment during an experimental awakening 4
hours after bedtime. Latency to persistent sleep and total
sleep time before and after awakening were recorded. The
primary residual sedation measure was a sleep latency test
conducted hourly from 4 to 7 hours after treatment.
Self-report measure of alertness and concentration and digit
symbol substitution tests were examined concurrently.
SETTING: Sleep disorders centers. PATIENTS: Thirty-seven
adults with sleep-maintenance insomnia. INTERVENTIONS:
Zaleplon 10 mg, zolpidem 10 mg, or placebo. MEASUREMENTS AND
RESULTS: Thirty-one patients had efficacy-evaluable data; 37
patients received at least 1 dose of study medication and
were included in the safety analysis. Compared with placebo,
latency to persistent sleep after both zaleplon and zolpidem
was shorter and total sleep time after administration of the
drugs was longer (overall p < .001, Dunnett p < .001 for all
posthoc comparisons). Significant differences from placebo
were not found with zaleplon in daytime-sedation measures.
At 4, 5, and 7 hours after zolpidem, sleep onset on sleep
latency testing was shorter than after placebo (overall p <
.001 for all, Dunnett tests for posthoc comparisons p <
.001, p < .001, p < .05, respectively). Self-report measures
of concentration (4, 5, and 6 hours, overall p < .05,
Dunnett p < .05 for each time point) and alertness (4 hours,
overall p < .05, Dunnett p < .05), and Digit Symbol
Substitution Test scores (4 and 5 hours, overall p < .001,
Dunnett p < .01 for both time points) after zolpidem were
also lower than with placebo. CONCLUSIONS: Zaleplon 10 mg
and zolpidem 10 mg effectively shorten sleep latency and
lengthen sleep duration after dosing, when administered
during experimental nocturnal awakening. Residual sedation
was not detected as little as 4 hours after zaleplon 10 mg,
whereas residual sedation was detected with zolpidem 10 mg
up to 7 hours after treatment. These findings suggest that
zaleplon may be an appropriate treatment for use when
patients awaken during the night and have difficulty
reinitiating sleep.},
Key = {fds281904}
}
@article{fds281900,
Author = {McCall, WV and Erman, M and Krystal, AD and Rosenberg, R and Scharf, M and Zammit, GK and Wessel, T},
Title = {A polysomnography study of eszopiclone in elderly patients
with insomnia.},
Journal = {Current Medical Research and Opinion},
Volume = {22},
Number = {9},
Pages = {1633-1642},
Year = {2006},
Month = {September},
ISSN = {0300-7995},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16968566},
Abstract = {OBJECTIVE: To evaluate the safety and efficacy of
eszopiclone 2 mg in elderly patients (aged 64-86 years) with
chronic insomnia. METHODS: This was a randomized,
double-blind, placebo-controlled 2-week study. Patients
meeting DSM-IV criteria for primary insomnia and screening
polysomnography criteria (wakefulness after sleep onset
[WASO] >or= 20 min and latency to persistent sleep >or= 20
min) were randomized to 2 weeks of nightly treatment with
eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy
was assessed using polysomnography (Nights 1, 2, 13, and 14)
and patient reports (Nights 1-14); safety was assessed using
adverse events, clinical labs, physical examination, and
vital signs. The mean of all efficacy results during the
double-blind period was used for the efficacy analysis.
RESULTS: Results indicated that eszopiclone was associated
with significantly shorter sleep onset, less WASO, higher
sleep efficiency, more total sleep time, and greater
patient-reported quality and depth of sleep scores than
placebo (p < 0.05 for all) with a trend in patient-reported
morning sleepiness (p = 0.07). Other measures of daytime
functioning (ability to function, daytime alertness, and
sense of well-being) were not significantly different
between the two treatment groups. Among patients who napped,
eszopiclone patients reported fewer naps (p = 0.03) and less
cumulative naptime (median: 98 min placebo, 70 min
eszopiclone, p = 0.07). Unpleasant taste, dry mouth,
somnolence, and dizziness were higher in the eszopiclone
group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in
the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively).
CONCLUSION: In this study, eszopiclone was well tolerated
and produced significant improvements in both
polysomnographic and patient-reported measures of sleep
maintenance, sleep induction, and sleep duration in elderly
patients with chronic primary insomnia.},
Doi = {10.1185/030079906X112741},
Key = {fds281900}
}
@article{fds281902,
Author = {Krystal, AD},
Title = {Psychiatric Comorbidity: The Case for Treating
Insomnia},
Journal = {Sleep Medicine Clinics},
Volume = {1},
Number = {3},
Pages = {359-365},
Publisher = {Elsevier BV},
Year = {2006},
Month = {September},
ISSN = {1556-407X},
url = {http://dx.doi.org/10.1016/j.jsmc.2006.06.007},
Abstract = {A review of studies of the treatment of insomnia occurring
in association with other psychiatric disorders suggests
that the secondary insomnia model fails to explain
adequately the relationship between insomnia and the
associated conditions and also fails to lead to optimal
clinical management. This literature demonstrates that both
initial adjunctive insomnia treatment and treatment of
residual insomnia has positive effects on the response to
antidepressant treatment. Published literature provides
strong support for a model in which insomnia occurring with
major depression is of high clinical relevance and an
important target for therapy. Whether treatment of insomnia
occurring with generalized anxiety disorder and alcoholism
affects outcome will be an important area for future
research. The literature on the treatment of comorbid
insomnia also establishes that perhaps the most fundamental
pillar of the secondary insomnia model, which has served as
a guide to clinical practice, has crumbled. Because chronic
insomnia was believed to be caused by psychiatric disorders,
effective treatment of those underlying psychiatric
disorders was expected to eliminate insomnia [3]. There is
now clear evidence that treatment of major depression, GAD,
and alcoholism frequently does not relieve the associated
chronic insomnia. The case for the treatment of insomnia
when comorbid with other psychiatric disorders is clear.
Effective treatment for each of the most important comorbid
psychiatric conditions often fails to alleviate the
associated insomnia. When comorbid insomnia is associated
with impairment in function or quality of life, treatment
specifically for that insomnia is needed. One factor that
seems likely to have obscured this issue and to have
prevented the observation of residual insomnia in the past
is that nearly all of the psychiatric disorders in question
were routinely treated with sedating agents (tricyclic or
other sedating antidepressants in major depression;
benzodiazepines or tricyclic or other sedating
antidepressants in anxiety disorders; tricyclic or other
sedating antidepressants in alcoholism), and these
medications probably were treating the associated insomnia.
Over time these disorders increasingly have been treated
with agents that are not sedating (SSRIs,
serotonin-norepinephrine reuptake inhibitors,
norepinephrine-dopamine reuptake inhibitors). The residual
insomnia has been most clearly observed in studies that have
included these agents. Although in some instances the
insomnia may reflect a sleep-disruptive side effect, the
observation that residual insomnia also is found in patients
who respond to cognitive behavioral therapy suggests
otherwise [21]. Nonetheless, the view that sedating
single-agent therapies might be addressing insomnia that
occurred in association with psychiatric disorders was
supported by the studies in which improvements in sleep were
noted with several benzodiazepine-related agents and
trazodone. Studies of other single-agent sedating
treatments, including tricyclic antidepressants, and
mirtazapine, would help in making clinical decisions when an
agent that addresses insomnia is indicated. These
considerations also suggest that the treatment of comorbid
insomnia with interventions that do not address insomnia,
such as cognitive behavioral therapy, SSRIs, bupropion, or
serotonin-norepinephrine reuptake inhibitors should be
accompanied by adjunctive insomnia therapy, particularly in
patients who have major depression and those at high risk or
with greater impairment in function. Very few combinations
of nonsedating treatments and insomnia therapies have been
studied. Insomnia agents that have been combined with
fluoxetine are eszopiclone, trazodone, zolpidem, and
clonazepam. Bupropion also has been combined with trazodone.
There is a need to investigate other combinations of
medications both for the treatment of the insomnia and the
associated psychiatric decision to provide an empiric basis
for making the clinical decisions needed for optimal
management of comorbid insomnia. © 2006 Elsevier Inc. All
rights reserved.},
Doi = {10.1016/j.jsmc.2006.06.007},
Key = {fds281902}
}
@article{fds281901,
Author = {Fava, M and McCall, WV and Krystal, A and Wessel, T and Rubens, R and Caron, J and Amato, D and Roth, T},
Title = {Eszopiclone co-administered with fluoxetine in patients with
insomnia coexisting with major depressive
disorder.},
Journal = {Biological Psychiatry},
Volume = {59},
Number = {11},
Pages = {1052-1060},
Year = {2006},
Month = {June},
ISSN = {0006-3223},
url = {http://dx.doi.org/10.1016/j.biopsych.2006.01.016},
Abstract = {BACKGROUND: Insomnia and major depressive disorder (MDD) can
coexist. This study evaluated the effect of adding
eszopiclone to fluoxetine. METHODS: Patients who met DSM-IV
criteria for both MDD and insomnia (n = 545) received
morning fluoxetine and were randomized to nightly
eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks.
Subjective sleep and daytime function were assessed weekly.
Depression was assessed with the 17-item Hamilton Rating
Scale for Depression (HAM-D-17) and the Clinical Global
Impression Improvement (CGI-I) and Severity items (CGI-S).
RESULTS: Patients in the ESZ+FLX group had significantly
decreased sleep latency, wake time after sleep onset (WASO),
increased total sleep time (TST), sleep quality, and depth
of sleep at all double-blind time points (all p < .05).
Eszopiclone co-therapy also resulted in: significantly
greater changes in HAM-D-17 scores at Week 4 (p = .01) with
progressive improvement at Week 8 (p = .002); significantly
improved CGI-I and CGI-S scores at all time points beyond
Week 1 (p < .05); and significantly more responders (59% vs.
48%; p = .009) and remitters (42% vs. 33%; p = .03) at Week
8. Treatment was well tolerated, with similar adverse event
and dropout rates. CONCLUSIONS: In this study,
eszopiclone/fluoxetine co-therapy was relatively well
tolerated and associated with rapid, substantial, and
sustained sleep improvement, a faster onset of
antidepressant response on the basis of CGI, and a greater
magnitude of the antidepressant effect.},
Doi = {10.1016/j.biopsych.2006.01.016},
Key = {fds281901}
}
@article{fds281898,
Author = {Walsh, JK and Perlis, M and Rosenthal, M and Krystal, A and Jiang, J and Roth, T},
Title = {Tiagabine increases slow-wave sleep in a dose-dependent
fashion without affecting traditional efficacy measures in
adults with primary insomnia.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {2},
Number = {1},
Pages = {35-41},
Year = {2006},
Month = {January},
ISSN = {1550-9389},
Abstract = {INTRODUCTION: This study evaluated dose-response effects of
tiagabine on sleep in adults with primary insomnia. METHODS:
Men and women with primary insomnia (DSM-IV-TR) were
randomly assigned to receive tiagabine 4, 6, 8, 10 mg or
placebo in a randomized, double-blind, parallel-group study.
Efficacy was assessed using polysomnography and self-report
measures. Safety analyses included measures of residual
sedation and adverse events. RESULTS: A total of 232
patients (31% men; mean age 44.3 years) received study drug.
No significant differences were observed between tiagabine
and placebo in wake after sleep onset, latency to persistent
sleep, or total sleep time. Significantly greater increases
from baseline in slow-wave sleep (stages 3 and 4) were found
with the 3 highest doses of tiagabine compared with placebo
(p < .01). Stage 1 sleep showed a significantly greater
decrease from baseline for all doses of tiagabine than for
placebo (p < .01). Self-report measures of sleep and daytime
function did not differ from placebo, except for poorer
ratings on the 10-mg dose. Similarly, psychomotor
performance on the 10-mg dose was worsened compared with
placebo. Tiagabine was generally well tolerated; dizziness
and nausea were the most common adverse events, particularly
at the 2 higher doses. CONCLUSIONS: In adults with primary
insomnia, tiagabine significantly increased slow-wave sleep
in a dose-dependent manner with a corresponding significant
decrease in Stage 1 sleep, whereas no significant
differences were observed in wake after sleep onset, latency
to persistent sleep, or total sleep time compared with
placebo.},
Key = {fds281898}
}
@article{fds281899,
Author = {Ancoli-Israel, S and Folks, DG and Krystal, AD and McCall,
WV},
Title = {Response to Dr. Finucane [2]},
Journal = {Journal of the American Geriatrics Society},
Volume = {54},
Number = {1},
Pages = {170-172},
Publisher = {WILEY},
Year = {2006},
Month = {January},
ISSN = {0002-8614},
url = {http://dx.doi.org/10.1111/j.1532-5415.2005.00575_1.x},
Doi = {10.1111/j.1532-5415.2005.00575_1.x},
Key = {fds281899}
}
@article{fds281903,
Author = {Krystal, AD and Rogers, S and Fitzgerald, MA},
Title = {Long-Term Pharmacotherapy in the Management of Chronic
Insomnia},
Journal = {The Journal for Nurse Practitioners},
Volume = {2},
Number = {9},
Pages = {S621-S632},
Publisher = {Elsevier BV},
Year = {2006},
Month = {January},
ISSN = {1555-4155},
url = {http://dx.doi.org/10.1016/j.nurpra.2006.08.003},
Abstract = {Chronic insomnia is common among primary care patients and
often necessitates long-term management. The available
treatment options for the clinical care of such patients are
limited. Medication management is the most common therapy
for this condition; however, this practice was hindered
until recently by clinical guidelines that discouraged the
prescription of the medications approved by the Food and
Drug Administration for longer than 4 weeks. Further, few
research studies have been conducted on the longer-term
medication management of insomnia that might allow
clinicians to assess the expected risks and benefits of
longer-term therapy. Recent research, however, indicates
that longer-term treatment with some agents may be safe and
effective. This article reviews these studies and discusses
them in the context of the diagnostic steps to consider when
deciding whether to initiate or continue pharmacotherapy for
insomnia. © 2006 American College of Nurse
Practitioners.},
Doi = {10.1016/j.nurpra.2006.08.003},
Key = {fds281903}
}
@article{fds311682,
Author = {Ancoli-Israel, S and Folks, DG and Krystal, AD and McCall,
WV},
Title = {Advertising the new hypnotics - Response to Dr.
Finucane},
Journal = {Journal of the American Geriatrics Society},
Volume = {54},
Number = {1},
Pages = {170-172},
Publisher = {BLACKWELL PUBLISHING},
Year = {2006},
Month = {January},
ISSN = {0002-8614},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000234404300029&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311682}
}
@article{fds281897,
Author = {Edinger, JD and Wohlgemuth, WK and Krystal, AD and Rice,
JR},
Title = {Behavioral insomnia therapy for fibromyalgia patients: a
randomized clinical trial.},
Journal = {Archives of Internal Medicine},
Volume = {165},
Number = {21},
Pages = {2527-2535},
Year = {2005},
Month = {November},
ISSN = {0003-9926},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16314551},
Abstract = {BACKGROUND: Insomnia is common and debilitating to
fibromyalgia (FM) patients. Cognitive-behavioral therapy
(CBT) is effective for many types of patients with insomnia,
but has yet to be tested with FM patients. This study
compared CBT with an alternate behavioral therapy and usual
care for improving sleep and other FM symptoms. METHODS:
This randomized clinical trial enrolled 47 FM patients with
chronic insomnia complaints. The study compared CBT, sleep
hygiene (SH) instructions, and usual FM care alone. Outcome
measures were subjective (sleep logs) and objective
(actigraphy) total sleep time, sleep efficiency, total wake
time, sleep latency, wake time after sleep onset, and
questionnaire measures of global insomnia symptoms, pain,
mood, and quality of life. RESULTS: Forty-two patients
completed baseline and continued into treatment. Sleep logs
showed CBT-treated patients achieved nearly a 50% reduction
in their nocturnal wake time by study completion, whereas SH
therapy- and usual care-treated patients achieved only 20%
and 3.5% reductions on this measure, respectively. In
addition, 8 (57%) of 14 CBT recipients met strict subjective
sleep improvement criteria by the end of treatment compared
with 2 (17%) of 12 SH therapy recipients and 0% of the usual
care group. Comparable findings were noted for similar
actigraphic improvement criteria. The SH therapy patients
showed favorable outcomes on measures of pain and mental
well-being. This finding was most notable in an SH therapy
subgroup that self-elected to implement selected CBT
strategies. CONCLUSIONS: Cognitive-behavioral therapy
represents a promising intervention for sleep disturbance in
FM patients. Larger clinical trials of this intervention
with FM patients seem warranted.},
Doi = {10.1001/archinte.165.21.2527},
Key = {fds281897}
}
@article{fds281896,
Author = {Roth, T and Walsh, JK and Krystal, A and Wessel, T and Roehrs,
TA},
Title = {An evaluation of the efficacy and safety of eszopiclone over
12 months in patients with chronic primary
insomnia.},
Journal = {Sleep Medicine},
Volume = {6},
Number = {6},
Pages = {487-495},
Year = {2005},
Month = {November},
ISSN = {1389-9457},
url = {http://dx.doi.org/10.1016/j.sleep.2005.06.004},
Abstract = {BACKGROUND AND PURPOSE: A double-blind placebo-controlled
study of eszopiclone found significant, sustained
improvement in sleep and daytime function. The 6-month
open-label extension phase is described herein. PATIENTS AND
METHODS: Adults (21-64) with primary insomnia who reported
sleep duration <6.5 h/night or sleep latency >30 min/night
were included. Patient-reported endpoints included sleep and
daytime function. Safety and compliance were assessed at
monthly clinic visits. The final double-blind month was used
as the baseline for efficacy analyses of the open-label
period. RESULTS: Patients who were initially randomized to
double-blind placebo and then switched to open-label
eszopiclone (n=111) significantly reported the following:
(1) decreased sleep latency, wake time after sleep onset,
and number of awakenings; (2) increased total sleep time and
sleep quality; and (3) improved ratings of daytime ability
to function, alertness and sense of physical well-being
compared to baseline (P<or=0.0001 all monthly endpoints).
There was no evidence of tolerance on any measure in either
group. These subjects (n=360) sustained the double-blind
treatment gains for all sleep and daytime parameters, with
further significant improvement in a number of measures.
Eszopiclone was well tolerated in both groups; unpleasant
taste was the only undesirable effect reported by >5% of
patients. CONCLUSIONS: The significant improvements in sleep
and daytime function were evident in those switched from
double-blind placebo to 6 months of open-label eszopiclone
therapy and were sustained during the 6 months of open-label
treatment for those receiving prior double-blind
eszopiclone. During 12 months of nightly treatment,
eszopiclone 3mg was well tolerated; tolerance was not
observed.},
Doi = {10.1016/j.sleep.2005.06.004},
Key = {fds281896}
}
@article{fds281891,
Author = {Krystal, AD},
Title = {The effect of insomnia definitions, terminology, and
classifications on clinical practice.},
Journal = {Journal of the American Geriatrics Society},
Volume = {53},
Number = {7 Suppl},
Pages = {S258-S263},
Year = {2005},
Month = {July},
ISSN = {0002-8614},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15982374},
Abstract = {There is a need for newer, more clinically useful
classifications for insomnia. Identification of specific
subtypes of insomnia helps anchor research, allows for
prediction of prognosis/course of the condition, and may
allow for individualization of treatment. Existing
classifications differ, and many terms remain inadequately
defined, which leads to diagnostic confusion. Historically,
insomnia has been classified according to symptom type,
symptom duration, and underlying cause, but these
classifications have not been based on evidence of their
utility, and newer research suggests the need for change.
Symptoms may include difficulty falling asleep, trouble
staying asleep, and not feeling restored by sleep, although
it has not been clear that it is possible to identify
distinct subtypes of patients by symptom or that
distinguishing symptom type affects the course of clinical
treatment. Classification of insomnia by duration most
commonly involves three categories: transient (no more than
a few days), short-term (up to 3 weeks), and long-term (more
than 3 weeks). This categorization is of uncertain utility
and has been primarily based on nonempiric concerns about
treatment with sedative-hypnotic medications for periods
longer than several weeks. The subtyping of insomnia in
terms of whether there is an identifiable underlying cause
such as a psychiatric or medical illness was based on an
unproven assumption that in most instances other disorders
caused insomnia. Recent studies suggest the need to revisit
these classification strategies. Evidence that symptom types
typically overlap and change over time complicates the
categorization of subjects by whether they have difficulty
falling asleep or staying asleep or have nonrestorative
sleep. New studies of the treatment of chronic insomnia
change the perspective on duration of treatment and, as a
result, classification of duration of disease. Two studies
of nightly pharmacotherapy for insomnia including more than
800 insomnia patients have not identified any increase in
the risks after 3 to 4 weeks of treatment. In addition,
nonpharmacological treatments demonstrate long-lasting
efficacy in patients with chronic insomnia, and the
development of abbreviated cognitive-behavioral therapies,
which are particularly well suited to primary care practice,
have improved their applicability. Newer studies of the
relationships between insomnia and associated medical and
psychiatric conditions undermine the notion that insomnia is
always a symptom and caused by an underlying condition. They
suggest that, although it is important to identify and treat
these conditions, this may not be sufficient to alleviate
the insomnia, which may adversely affect the course of the
associated disorder. As a result, treatment targeted
specifically to the insomnia should be considered. All of
these developments point to an increasing ability to tailor
therapy to the particular needs of patients and to optimize
the clinical management of insomnia.},
Doi = {10.1111/j.1532-5415.2005.53391.x},
Key = {fds281891}
}
@article{fds281895,
Author = {Wohlgemuth, WK and Krystal, AD},
Title = {Hypnotics should be considered for the initial treatment of
chronic insomnia. Pro.},
Journal = {Journal of Clinical Sleep Medicine : Jcsm : Official
Publication of the American Academy of Sleep
Medicine},
Volume = {1},
Number = {2},
Pages = {120-124},
Year = {2005},
Month = {April},
ISSN = {1550-9389},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17561623},
Key = {fds281895}
}
@article{fds281893,
Author = {Krystal, AD},
Title = {The possibility of preventing functional impairment due to
sleep loss by pharmacologically enhancing
sleep.},
Journal = {Sleep},
Volume = {28},
Number = {1},
Pages = {16-17},
Year = {2005},
Month = {January},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15700715},
Key = {fds281893}
}
@article{fds281894,
Author = {McCall, WV and Perlis, ML and Tu, X and Groman, AE and Krystal, A and Walsh, JK},
Title = {A comparison of placebo and no-treatment during a hypnotic
clinical trial},
Journal = {International Journal of Clinical Pharmacology and
Therapeutics},
Volume = {43},
Number = {8},
Pages = {355-359},
Publisher = {Dustri-Verlgag Dr. Karl Feistle},
Year = {2005},
ISSN = {0946-1965},
url = {http://dx.doi.org/10.5414/cpp43355},
Abstract = {Objective: Sleep parameters commonly improve during placebo
treatment in insomnia clinical trials. We examined whether
the improvement seen with placebo was related to taking
pills or other non-specific factors. Method: 95 insomniacs
took either a placebo pill (pill+) or no pill (pill-) on
nights of their choosing over 12 weeks. Results: Pills were
consumed on about half of the nights. Consistent improvement
was seen with reduced reported sleep latency, wakefulness
after sleep onset, number of awakenings, and total sleep
time over the 12 weeks for both the pill+ and pill-
condition. A difference between pill+ and pill- was detected
only for total sleep time, and this difference favored
pill+. Conclusions: This study suggests that improvement
seen during placebo treatment is more related to
non-specific factors of participating in clinical trial than
to pill taking behavior. © 2005 Dustri-Verlag Dr. K.
Feistle.},
Doi = {10.5414/cpp43355},
Key = {fds281894}
}
@article{fds281889,
Author = {Krystal, AD and Roth, T},
Title = {Definitions, measurements, and management in
insomnia},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65},
Number = {SUPPL. 8},
Pages = {5-7},
Year = {2004},
Month = {December},
ISSN = {0160-6689},
Key = {fds281889}
}
@article{fds281892,
Author = {Perlis, ML and McCall, WV and Krystal, AD and Walsh,
JK},
Title = {Long-term, non-nightly administration of zolpidem in the
treatment of patients with primary insomnia.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65},
Number = {8},
Pages = {1128-1137},
Year = {2004},
Month = {August},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15323600},
Abstract = {INTRODUCTION: While it is common practice that hypnotics are
used on a non-nightly basis, few investigations have been
undertaken to evaluate the efficacy of the intermittent
dosing strategy. The present study was designed to further
evaluate this issue within a large scale, double-blind,
placebo-controlled, long-term trial. METHOD: Patients who
met DSM-IV criteria for primary insomnia participated in the
study from January 2000 through October 2001. Patients were
randomly assigned to 1 of 2 treatment groups (zolpidem 10 mg
or placebo) for a period of 12 weeks. Ten pills were
provided in foil packs on an every-other-week basis, and
patients were instructed to take no fewer than 3 and no more
than 5 pills per week. Sleep was evaluated daily with sleep
diaries. Pill use was recorded in the sleep diaries.
RESULTS: 199 patients (mean +/- SD age = 41.0 +/- 12.8
years; 71% female) were randomly assigned to treatment. On
mean, patients receiving zolpidem exhibited (vs. baseline) a
42% decrease in sleep latency, a 52% reduction in number of
awakenings, a 55% decrease in wake time after sleep onset,
and a 27% increase in total sleep time. These positive
clinical gains did not diminish with time and were not
associated with dose escalation. There was also no evidence
of rebound insomnia. CONCLUSIONS: Over a period of 12 weeks
of intermittent treatment with zolpidem, sleep continuity
was significantly improved, the clinical gains were
sustained, and there was no evidence of subjective rebound
insomnia between doses or increases in the amount of
medication used during the study interval.},
Doi = {10.4088/jcp.v65n0816},
Key = {fds281892}
}
@article{fds281973,
Author = {Singh, J and Zarate, CA and Krystal, AD},
Title = {Case report: Successful riluzole augmentation therapy in
treatment-resistant bipolar depression following the
development of rash with lamotrigine.},
Journal = {Psychopharmacology},
Volume = {173},
Number = {1-2},
Pages = {227-228},
Year = {2004},
Month = {April},
ISSN = {0033-3158},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14722708},
Keywords = {Adult • Antidepressive Agents • Bipolar Disorder
• Drug Synergism • Exanthema • Excitatory
Amino Acid Antagonists • Humans • Male •
Riluzole • Treatment Outcome • Triazines •
adverse effects* • chemically induced* •
complications • drug therapy • drug therapy*
• therapeutic use • therapeutic
use*},
Language = {eng},
Doi = {10.1007/s00213-003-1756-8},
Key = {fds281973}
}
@article{fds311677,
Author = {Krystal, AD and Walsh, JK and Laska, E and Caron, J and Amato, DA and Wessel, TC and Roth, T},
Title = {The Sustained 6-Month Efficacy of Eszopiclone in the
Treatment of Chronic Insomnia},
Journal = {Sleep},
Volume = {27},
Number = {2},
Pages = {346-347},
Publisher = {Oxford University Press (OUP)},
Year = {2004},
Month = {March},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000223168800027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Doi = {10.1093/sleep/27.2.346},
Key = {fds311677}
}
@article{fds281969,
Author = {Krystal, AD and Roth, T},
Title = {Introduction: Definitions, measurements, and management in
insomnia.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65 Suppl 8},
Pages = {5-7},
Year = {2004},
Month = {January},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15153061},
Keywords = {Chronic Disease • Cost of Illness • Humans •
Hypnotics and Sedatives • Personality Inventory •
Polysomnography • Sleep Initiation and Maintenance
Disorders • Terminology • diagnosis* • drug
therapy • psychology • therapeutic
use},
Key = {fds281969}
}
@article{fds311680,
Author = {Ancoli-Israel, S and Benca, RM and Edinger, JD and Krystal, AD and Mendelson, W and Moldofsky, H and Petrie, J and Roth, T and Walsh, JK and Winkelman, J},
Title = {Changing how we think about insomnia},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65},
Pages = {44-46},
Publisher = {PHYSICIANS POSTGRADUATE PRESS},
Year = {2004},
Month = {January},
ISSN = {0160-6689},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000221956100007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311680}
}
@article{fds281890,
Author = {Krystal, AD},
Title = {Depression and insomnia in women.},
Journal = {Clinical Cornerstone},
Volume = {6 Suppl 1B},
Pages = {S19-S28},
Year = {2004},
ISSN = {1098-3597},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15457812},
Abstract = {Depression and insomnia are both significantly more
prevalent in women than in men. Risks appear linked to
fluctuations and transitions in gonadal hormones during
various phases of women's lives, with the risk of depression
greatest during the period from menarche to menopause.
Increased risks of both insomnia and depression also
coincide with the late luteal phase of the menstrual cycle,
during and after pregnancy, and during the
peri-/postmenopausal period. Gonadal hormones exert
significant effects on the neurohumoral systems most
intimately associated with depression and insomnia, with
corresponding implications for treatment. Medications
related to the serotonin system-the selective serotonin
reuptake inhibitors, or SSRIs-appear to be uniquely
effective in the treatment of insomnia and depression
experienced by women. SSRIs and the nonbenzodiazepine
receptor agonists are generally useful as first-line
treatments in a number of circumstances; hormone replacement
therapies can also be considered. Behavioral therapies for
insomnia may be particularly relevant for postpartum
patients because of safety concerns and to prevent the
development of autonomous chronic insomnia, which may also
increase the risk of depression. In light of the high risk
of relapse and high likelihood of comorbidity, it is crucial
to effectively treat both insomnia and depression in women.
However, few data exist for many key areas related to the
treatment of these disorders in women, and research is
greatly needed.},
Doi = {10.1016/s1098-3597(04)80022-x},
Key = {fds281890}
}
@article{fds281971,
Author = {Krystal, AD},
Title = {The changing perspective on chronic insomnia
management.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65 Suppl 8},
Pages = {20-25},
Year = {2004},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15153064},
Keywords = {Antidepressive Agents • Antipsychotic Agents •
Chronic Disease • Clinical Trials as Topic •
Cognitive Therapy • Histamine H1 Antagonists •
Humans • Hypnotics and Sedatives • Sleep
Initiation and Maintenance Disorders • Terminology as
Topic • Treatment Outcome • classification •
drug therapy • therapeutic use •
therapy*},
Abstract = {A particular challenge in the treatment of insomnia is
management of chronic insomnia, which occurs in a
substantial portion of the population. A number of factors
suggest the importance of identifying this condition as
distinct from short-term insomnia in clinical practice and
treating these 2 entities differently. Yet, there is no
consensus about how to make this distinction or how to
manage patients beyond the short term. Clinicians have been
without guidance as to how to address the significant
challenges associated with treating patients long term with
any of the currently available treatments. In recent years,
however, new studies have suggested the emergence of a
changing perspective on the management of chronic insomnia.
These studies have begun to provide an empirical basis for
making decisions in the treatment of patients with chronic
insomnia. They suggest that clinical practice is evolving
toward an improved capacity to treat insomnia, with
treatments that can safely lead to sustained
efficacy.},
Language = {eng},
Key = {fds281971}
}
@article{fds281975,
Author = {Ancoli-Israel, S and Benca, RM and Edinger, JD and Krystal, AD and Mendelson, W and Moldofsky, H and Petrie, J and Roth, T and Walsh, JK and Winkelman, J and Special Issues Board Panel
Members},
Title = {Panel discussion: changing how we think about
insomnia.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {65 Suppl 8},
Pages = {44-46},
Year = {2004},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15153067},
Keywords = {Age Factors • Aged • Attitude of Health Personnel
• Depressive Disorder • Humans • Pain •
Pain Management • Physician's Practice Patterns •
Sleep Initiation and Maintenance Disorders* •
classification • diagnosis • therapy},
Language = {eng},
Key = {fds281975}
}
@article{fds281974,
Author = {Krystal, AD and Walsh, JK and Laska, E and Caron, J and Amato, DA and Wessel, TC and Roth, T},
Title = {Sustained efficacy of eszopiclone over 6 months of nightly
treatment: results of a randomized, double-blind,
placebo-controlled study in adults with chronic
insomnia.},
Journal = {Sleep},
Volume = {26},
Number = {7},
Pages = {793-799},
Year = {2003},
Month = {November},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14655910},
Keywords = {Adult • Aged • Azabicyclo Compounds • Chronic
Disease • Circadian Rhythm* • Double-Blind Method
• Female • Humans • Hypnotics and Sedatives
• Male • Middle Aged • Piperazines •
Sleep Initiation and Maintenance Disorders • Time
Factors • Wakefulness • drug effects • drug
therapy* • pharmacology • therapeutic
use*},
Abstract = {STUDY OBJECTIVES: To determine the long-term efficacy of
eszopiclone in patients with chronic insomnia. DESIGN:
Randomized, double-blind, multicenter, placebo-controlled.
SETTING: Out-patient, with monthly visits. PATIENTS: Aged 21
to 69 years meeting DSM IV criteria for primary insomnia and
reporting less than 6.5 hours of sleep per night, and/or a
sleep latency of more than 30 minutes each night for at
least 1 month before screening. INTERVENTIONS: Eszopiclone 3
mg (n = 593) or placebo (n = 195), nightly for 6 months
MEASUREMENTS AND RESULTS: Efficacy was evaluated weekly
using an interactive voice-response system. Endpoints
included sleep latency; total sleep time; number of
awakenings; wake time after sleep onset; quality of sleep;
and next-day ratings of ability to function, daytime
alertness, and sense of physical well-being. At the first
week and each month for the study duration, eszopiclone
produced significant and sustained improvements in sleep
latency, wake time after sleep onset, number of awakenings,
number of nights awakened per week, total sleep time, and
quality of sleep compared with placebo (P < or = 0.003).
Monthly ratings of next-day function, alertness, and sense
of physical well-being were also significantly better with
the use of eszopiclone than with placebo (P < or = 0.002).
There was no evidence of tolerance, and the most common
adverse events were unpleasant taste and headache.
CONCLUSIONS: Throughout 6 months, eszopiclone improved all
of the components of insomnia as defined by DSM-IV,
including patient ratings of daytime function. This
placebo-controlled study of eszopiclone provides compelling
evidence that long-term pharmacologic treatment of insomnia
is efficacious.},
Language = {eng},
Doi = {10.1093/sleep/26.7.793},
Key = {fds281974}
}
@article{fds281970,
Author = {Edinger, JD and Krystal, AD},
Title = {Subtyping primary insomnia: is sleep state misperception a
distinct clinical entity?},
Journal = {Sleep Medicine Reviews},
Volume = {7},
Number = {3},
Pages = {203-214},
Year = {2003},
Month = {June},
ISSN = {1087-0792},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12927120},
Keywords = {Diagnosis, Differential • Diagnostic Errors •
Humans • Polysomnography • Sleep Initiation and
Maintenance Disorders • classification* •
diagnosis*},
Abstract = {Among the range of primary insomnia subtypes, those assigned
such labels as subjective insomnia or sleep state
misperception historically have been among the most
intriguing yet challenging to understand and manage
clinically. Such patients who produce seemingly normal
polysomnograms often present rather compelling and, at
times, dramatic sleep complaints. Our earliest formal sleep
nosology included a separate diagnostic category for such
individuals, but little research has been devoted to this
insomnia subtype in the 20 years since this classification
scheme was proposed. As a result, use of diagnoses such as
subjective insomnia or sleep state misperception have
remained controversial. The current article reviews this
controversy and highlights the major criticisms forged
against subdividing primary insomnia into objective and
subjective subtypes. Subsequently, the relative merits of
these criticisms are considered in view of early and recent
findings vis-à-vis the subjective/objective insomnia
dichotomy. Although available data are not conclusive, there
appears to be sufficient evidence to suggest subjective and
objective insomnia subtypes may suffer from distinctive
forms of sleep-related pathophysiology. We conclude by
advocating continued study of the subjective insomnia
phenomenon and by providing specific directions for relevant
future research.},
Language = {eng},
Doi = {10.1053/smrv.2002.0253},
Key = {fds281970}
}
@article{fds281888,
Author = {Cellucci, CJ and Albano, AM and Rapp, PE and Krystal,
AD},
Title = {Quantitative determination of abrupt changes in dynamical
systems: Illustration via identification of seizure
termination in generalized tonic-clonic seizure EEG
data},
Journal = {International Journal of Bifurcation and
Chaos},
Volume = {13},
Number = {9},
Pages = {2641-2655},
Publisher = {World Scientific Pub Co Pte Lt},
Year = {2003},
Month = {January},
url = {http://dx.doi.org/10.1142/S0218127403008132},
Abstract = {We discuss key theoretical and practical issues related to
the identification of transitions in dynamical systems in
real-time. We focus on the choice of candidate measures and
optimization of decision thresholds for candidate measures.
To illustrate these issues we develop and test a procedure
for identifying one particular transition, the end-point of
seizures in two-channel electroencephalographic data
recorded during generalized tonic-clonic seizures. Data from
twenty-eight seizures were available and used to develop and
test the procedure in terms of the agreement between the
computationally identified seizure end-point compared
against the ratings of an expert clinical
electroencephalographer. Generalizations to multivariate
seizure onset detection and to seizure prediction are
described.},
Doi = {10.1142/S0218127403008132},
Key = {fds281888}
}
@article{fds281972,
Author = {Krystal, AD},
Title = {Insomnia in women.},
Journal = {Clinical Cornerstone},
Volume = {5},
Number = {3},
Pages = {41-50},
Year = {2003},
ISSN = {1098-3597},
url = {http://www.ncbi.nlm.nih.gov/pubmed/14626540},
Keywords = {Anxiety Disorders • Chronic Disease • Climacteric
• Comorbidity • Depression • Diagnostic and
Statistical Manual of Mental Disorders • Female •
Humans • Postmenopause • Pregnancy •
Prevalence • Sex Distribution • Sleep Initiation
and Maintenance Disorders • epidemiology •
epidemiology* • therapy*},
Abstract = {Insomnia is a highly prevalent disorder that can lead to
substantial impairments in quality of life and functional
capacity. This condition occurs significantly more
frequently in women than men. An important contributing
factor is that insomnia can occur in association with
hormonal changes that are unique to women, such as those of
menopause or the late-luteal phase of the menstrual cycle.
Another consideration is that women are more likely to
suffer from major depression and anxiety disorders, which
are also associated with insomnia. The reasons are unclear
as are the reasons why women are at increased risk of
primary insomnia. These conditions are frequently
encountered in clinical practice and present a challenge to
the practitioner because there is a striking lack of
research data to serve as a guide. For example, there are no
published studies to indicate how to safely and effectively
manage insomnia that often occurs late in pregnancy. This
article reviews the available literature related to these
conditions with a focus on the epidemiologic data and
diagnosis and treatment of insomnia and highlights the need
for further research.},
Language = {eng},
Doi = {10.1016/s1098-3597(03)90034-2},
Key = {fds281972}
}
@article{fds281981,
Author = {Krystal, AD and Weiner, RD and Dean, MD and Lindahl, VH and Tramontozzi,
LA and Falcone, G and Coffey, CE},
Title = {Comparison of seizure duration, ictal EEG, and cognitive
effects of ketamine and methohexital anesthesia with
ECT.},
Journal = {The Journal of Neuropsychiatry and Clinical
Neurosciences},
Volume = {15},
Number = {1},
Pages = {27-34},
Year = {2003},
ISSN = {0895-0172},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12556568},
Keywords = {Aged • Aged, 80 and over • Anesthesia,
Intravenous* • Bipolar Disorder • Depressive
Disorder, Major • Electroconvulsive Therapy* •
Electroencephalography • Female • Humans •
Ketamine* • Male • Methohexital* • Middle
Aged • Orientation • Psychotic Disorders •
Retrospective Studies • Signal Processing,
Computer-Assisted • administration & dosage •
adverse effects • drug effects • drug effects*
• therapy*},
Abstract = {The authors retrospectively compared the seizure duration,
ictal EEG, and cognitive side effects of ketamine and
methohexital anesthesia with ECT. This comparison was
carried out with data from consecutive index ECT treatments
that occurred immediately before and after a switch from
methohexital to ketamine in 36 patients. Ketamine was well
tolerated and prolonged seizure duration overall, but
particularly in those who had a seizure duration shorter
than 25 seconds with methohexital at the maximum available
stimulus intensity. Ketamine also increased midictal EEG
slow-wave amplitude. Thus, a switch to ketamine may be
useful when it is difficult to elicit a robust seizure.
Faster post-treatment reorientation with ketamine may
suggest a lower level of associated cognitive side
effects.},
Language = {eng},
Doi = {10.1176/jnp.15.1.27},
Key = {fds281981}
}
@article{fds281994,
Author = {Krystal, AD and Edinger, JD and Wohlgemuth, WK and Marsh,
GR},
Title = {NREM sleep EEG frequency spectral correlates of sleep
complaints in primary insomnia subtypes.},
Journal = {Sleep},
Volume = {25},
Number = {6},
Pages = {630-640},
Year = {2002},
Month = {September},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12224842},
Keywords = {Adult • Aged • Aged, 80 and over • Cognitive
Therapy • Double-Blind Method •
Electroencephalography* • Female • Humans •
Male • Middle Aged • Polysomnography • Sleep
Initiation and Maintenance Disorders • Sleep Stages
• Sleep, REM • diagnosis • epidemiology
• methods* • physiology • physiology* •
therapy*},
Abstract = {STUDY OBJECTIVES: To determine whether the frequency
spectrum of the sleep EEG is a physiologic correlate of 1)
the degree to which individuals with persistent primary
insomnia (PPI) underestimate their sleep time compared with
the traditionally scored polysomnogram (PSG) and 2) the
sleep complaints in PPI subjects who have relatively long
traditionally scored PSG sleep times and relatively greater
underestimation of sleep time. DESIGN: We compared EEG
frequency spectra from REM and NREM sleep in PPI subjects
subtyped as subjective insomnia sufferers (those with
relatively long total sleep time and relative
underestimation of sleep time compared with PSG), and
objective insomnia sufferers (those with relatively short
PSG total sleep time) with EEG frequency spectra in normals.
We also studied the correlation between these indices and
the degree of underestimation of sleep. Further, we
determined the degree to which sleep EEG indexes related to
sleep complaints. SETTING: Duke University Medical Center
Sleep Laboratory. PARTICIPANTS: Normal (N=20), subjective
insomnia (N=12), and objective insomnia (N=18) subjects.
INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Lower delta
and greater alpha, sigma, and beta NREM EEG activity were
found in the patients with subjective insomnia but not those
with objective insomnia, compared with the normal subjects.
These results were robust to changes in the subtyping
criteria. No effects were found for REM spectral indexes.
Less delta non- REM EEG activity predicted greater deviation
between subjective and PSG estimates of sleep time across
all subjects. For the subjective insomnia subjects,
diminished low-frequency and elevated higher frequency non-
REM EEG activity was associated with their sleep complaints.
CONCLUSIONS: NREM EEG frequency spectral indexes appear to
be physiologic correlates of sleep complaints in patients
with subjective insomnia and may reflect heightened arousal
during sleep.},
Language = {eng},
Key = {fds281994}
}
@article{fds311704,
Author = {Wohlgemuth, WK and Edinger, JD and Krystal, AD},
Title = {The best of both: Brief hypnotic use to enhance behavioral
insomnia therapy},
Journal = {Sleep},
Volume = {25},
Pages = {A360-A361},
Publisher = {AMER ACAD SLEEP MEDICINE},
Year = {2002},
Month = {April},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174927200504&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311704}
}
@article{fds311706,
Author = {Wohlgemuth, WK and Edinger, JD and Krystal, AD and Rice,
JR},
Title = {Behavioral insomnia therapy for patients with
fibromyalgia},
Journal = {Sleep},
Volume = {25},
Pages = {A384-A384},
Publisher = {AMER ACAD SLEEP MEDICINE},
Year = {2002},
Month = {April},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174927200539&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311706}
}
@article{fds311709,
Author = {Krystal, AD and Edinger, JD and Wohlgemuth, WK and Michaels,
C},
Title = {A within-subject study of the relationship of non-REM EEG
spectral amplitude and the agreement between subjective and
objective assessments of sleep time},
Journal = {Sleep},
Volume = {25},
Pages = {A33-A34},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2002},
Month = {April},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174927200045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311709}
}
@article{fds311687,
Author = {Krystal, AD and Perlis, ML and McCall, WV and Zammit, G and Hirshkowitz,
M},
Title = {Three-month non-nightly use of zolpidem for the treatment of
primary insomnia},
Journal = {Sleep},
Volume = {25},
Pages = {A68-A68},
Publisher = {AMER ACAD SLEEP MEDICINE},
Year = {2002},
Month = {April},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174927200094&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311687}
}
@article{fds311703,
Author = {Rossler, IB and Johnson, RC and Krystal, AD and Weiner, RD and Levin,
ED and Logue, P and Coffey, CE and Edwards, CL},
Title = {A naturalistic study of the effects of smoking on the
cognitive side effects of ECT.},
Journal = {The Journal of Ect},
Volume = {18},
Number = {1},
Pages = {64-64},
Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
Year = {2002},
Month = {March},
ISSN = {1095-0680},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174804700030&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311703}
}
@article{fds311708,
Author = {Vidal, F and Krystal, AD and Edinger, JD and Wohlgemuth,
WK},
Title = {Changes in sleep architecture and the sleep EEG with
aging.},
Journal = {American Journal of Geriatric Psychiatry},
Volume = {10},
Number = {2},
Pages = {96-97},
Publisher = {AMER PSYCHIATRIC PRESS, INC},
Year = {2002},
Month = {March},
ISSN = {1064-7481},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174795500213&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311708}
}
@article{fds281886,
Author = {Krystal, AD and Ressler, I},
Title = {The use of valerian in neuropsychiatry.},
Journal = {Cns Spectrums},
Volume = {6},
Number = {10},
Pages = {841-847},
Year = {2001},
Month = {October},
ISSN = {1092-8529},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15334039},
Abstract = {Valerian is a medicinal agent deriving from the plant
Valeriana officinalis L. We reviewed the available
literature on the use of valerian preparations in the
treatment of neuropsychiatric disorders. Preclinical studies
suggest that valerian has sedative and muscle-relaxant
effects. Few clinical trials with valerian have been carried
out in conditions other than insomnia. The insomnia studies
have methodologic shortcomings but suggest that some
preparations lead to significant subjective improvement in
sleep complaints with remarkably few side effects.
Furthermore, some evidence indicates that valerian
preparations may have a mechanism of action and clinical
characteristics that differ from the benzodiazepine-related
sedative/hypnotics, making them more suitable for long-term
use. If this safety profile and the plant's
sedative/hypnotic efficacy are confirmed in double-blind,
placebo-controlled trials with carefully and consistently
prepared valerian compounds, then those compounds would fill
an important and presently unfilled niche in the treatment
of insomnia.},
Doi = {10.1017/s1092852900001668},
Key = {fds281886}
}
@article{fds281996,
Author = {Sackeim, HA and Devanand, DP and Lisanby, SH and Nobler, MS and Prudic,
J and Heyer, EJ and Ornstein, E and Weiner, RD and Krystal, AD and Coffey,
CE and Greenberg, RM and Husain, M and Lite, MS and Fernandez, P and Gaines, GY},
Title = {Treatment of the modal patient: does one size fit nearly
all?},
Journal = {The Journal of Ect},
Volume = {17},
Number = {3},
Pages = {219-222},
Year = {2001},
Month = {September},
ISSN = {1095-0680},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11528317},
Keywords = {Amnesia • Anesthesia, General* • Dose-Response
Relationship, Drug • Electroconvulsive Therapy* •
Humans • Patient Care Planning • Practice
Guidelines* • Reference Values • Risk Factors
• adverse effects • etiology •
methods},
Doi = {10.1097/00124509-200109000-00015},
Key = {fds281996}
}
@article{fds281884,
Author = {Swartz, CM},
Title = {ECT failure rate among specific devices.},
Journal = {The American Journal of Psychiatry},
Volume = {158},
Number = {6},
Pages = {973-974},
Year = {2001},
Month = {June},
url = {http://dx.doi.org/10.1176/appi.ajp.158.6.973},
Doi = {10.1176/appi.ajp.158.6.973},
Key = {fds281884}
}
@article{fds311685,
Author = {Krystal, AD and Weiner, RD},
Title = {ECT failure rate among specific devices - Drs. Krystal and
Weiner reply},
Journal = {The American Journal of Psychiatry},
Volume = {158},
Number = {6},
Pages = {974-974},
Publisher = {AMER PSYCHIATRIC PRESS, INC},
Year = {2001},
Month = {June},
ISSN = {0002-953X},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000169175200045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311685}
}
@article{fds311707,
Author = {Krystal, AD and Edinger, JD and Wohlgemuth, WK and Marsh,
GR},
Title = {A pilot study of the sleep EEG power spectral effects of
behavioral therapy in primary insomniacs},
Journal = {Sleep},
Volume = {24},
Pages = {A62-A62},
Publisher = {AMER ACAD SLEEP MEDICINE},
Year = {2001},
Month = {April},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000168230900101&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311707}
}
@article{fds311672,
Author = {Krystal, AD and Holsinger, T and Weiner, RD and Steffens, DC and Coffey,
CE},
Title = {A naturalistic study of maintenance ECT: Implications for
optimizing the inter-treatment interval.},
Journal = {The Journal of Ect},
Volume = {17},
Number = {1},
Pages = {79-79},
Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
Year = {2001},
Month = {March},
ISSN = {1095-0680},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000167512900029&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311672}
}
@article{fds281887,
Author = {Prado, R and West, M and Krystal, AD},
Title = {Multichannel electroencephalographic analyses via dynamic
regression models with time-varying lag-lead
structure},
Journal = {Journal of the Royal Statistical Society. Series C, Applied
Statistics},
Volume = {50},
Number = {1},
Pages = {95-109},
Year = {2001},
Month = {January},
url = {http://dx.doi.org/10.1111/1467-9876.00222},
Abstract = {Multiple time series of scalp electrical potential activity
are generated routinely in electroencephalographic (EEG)
studies. Such recordings provide important non-invasive data
about brain function in human neuropsychiatric disorders.
Analyses of EEG traces aim to isolate characteristics of
their spatiotemporal dynamics that may be useful in
diagnosis, or may improve the understanding of the
underlying neurophysiology or may improve treatment through
identifying predictors and indicators of clinical outcomes.
We discuss the development and application of non-stationary
time series models for multiple EEG series generated from
individual subjects in a clinical neuropsychiatric setting.
The subjects are depressed patients experiencing generalized
tonic-clonic seizures elicited by electroconvulsive therapy
(ECT) as antidepressant treatment. Two varieties of models -
dynamic latent factor models and dynamic regression models -
are introduced and studied. We discuss model motivation and
form, and aspects of statistical analysis including
parameter identifiability, posterior inference and
implementation of these models via Markov chain Monte Carlo
techniques. In an application to the analysis of a typical
set of 19 EEG series recorded during an ECT seizure at
different locations over a patient's scalp, these models
reveal time-varying features across the series that are
strongly related to the placement of the electrodes. We
illustrate various model outputs, the exploration of such
time-varying spatial structure and its relevance in the ECT
study, and in basic EEG research in general.},
Doi = {10.1111/1467-9876.00222},
Key = {fds281887}
}
@article{fds136028,
Title = {Prado R, West M, Krystal AD Multichannel
electroencephalographic analyses via dynamic regression
models with time-varying lag-lead structure J. Royal
Statistical Society C-APP Part I. 2001;50:
95-109.},
Year = {2001},
Key = {fds136028}
}
@article{fds281992,
Author = {Krystal, AD and Holsinger, T and Weiner, RD and Coffey,
CE},
Title = {Prediction of the utility of a switch from unilateral to
bilateral ECT in the elderly using treatment 2 ictal EEG
indices.},
Journal = {The Journal of Ect},
Volume = {16},
Number = {4},
Pages = {327-337},
Year = {2000},
Month = {December},
ISSN = {1095-0680},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11314870},
Keywords = {Aged • Depressive Disorder • Electroconvulsive
Therapy • Electrodes • Electroencephalography*
• Female • Humans • Male • Middle Aged
• Predictive Value of Tests • Treatment Outcome
• methods* • therapy*},
Abstract = {BACKGROUND: The choice of whether to administer nondominant
unilateral (UL) or bilateral (BL) ECT remains controversial.
METHODS: A study in which moderately suprathreshold UL
nonresponders at treatment 6 were randomized to UL or BL ECT
offered the opportunity to explore whether ictal EEG indices
at treatment 2 might predict response to UL ECT, and also
which UL ECT nonresponders are likely to respond to BL ECT.
RESULTS: We found that less postictal suppression in
response to the second UL ECT stimulus was predictive of a
poorer subsequent therapeutic response to UL ECT, but of a
better therapeutic response if switched to BL ECT. A
multivariate ictal EEG model was developed that had a
significant capacity to differentiate those who will respond
to UL ECT versus those who will not respond to UL ECT, but
who will be therapeutic responders when switched to BL ECT.
CONCLUSIONS: This study raises the possibility that ictal
EEG indices at treatment 2 may identify situations when UL
ECT is physiologically and therapeutically inadequate, and
when BL ECT is likely to be more effective. The
determination of whether such predictive physiologic models
are of clinical utility for the prediction of outcome awaits
further study.},
Language = {eng},
Doi = {10.1097/00124509-200012000-00002},
Key = {fds281992}
}
@article{fds282005,
Author = {Krystal, AD and Weiner, RD and Lindahl, V and Massie,
R},
Title = {The development and retrospective testing of an
electroencephalographic seizure quality-based stimulus
dosing paradigm with ECT.},
Journal = {The Journal of Ect},
Volume = {16},
Number = {4},
Pages = {338-349},
Year = {2000},
Month = {December},
ISSN = {1095-0680},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11314871},
Keywords = {Adult • Aged • Depressive Disorder •
Electroconvulsive Therapy • Electroencephalography*
• Female • Humans • Male • Middle Aged
• Models, Biological* • Predictive Value of Tests
• Retrospective Studies • Seizures •
Treatment Outcome • etiology* • methods* •
physiopathology • therapy*},
Abstract = {The optimization of electroconvulsive therapy (ECT) stimulus
dosing remains uncertain. Previous work suggests the
potential utility of ictal EEG models of seizure adequacy,
but such models have never been tested for their ability to
improve the clinical dosing of ECT treatments. Using data
from 149 depressed patients, the authors developed an ictal
electroencephalographic (EEG) model that can discriminate
seizures produced by more therapeutically effective and less
efficacious types of stimuli. They retrospectively
determined how stimulus dosing according to this seizure
adequacy-based model would have differed from that actually
used in an additional 61 patients who received ECT according
to a standard clinical dose-titration and EEG seizure
duration-based dosing strategy. Although the model indicated
an increase in stimulus intensity at some point during the
ECT treatment course in 23 of 61 patients, only 5 of these
23 actually received a clinical increase in stimulus
intensity. The patients who did not receive this increase
had a significantly diminished therapeutic response compared
with the other patients. Conversely, the model also
indicated that an increase in stimulus intensity that
occurred clinically might have been unnecessary to achieve
therapeutic efficacy in 11% of the patients. This study
provides preliminary evidence that ictal EEG models have the
potential to make clinically relevant seizure adequacy
distinctions among ECT treatments. Further prospective work
is indicated to determine the clinical utility of such
models.},
Language = {eng},
Doi = {10.1097/00124509-200012000-00003},
Key = {fds282005}
}
@article{fds281987,
Author = {Krystal, AD and Dean, MD and Weiner, RD and Tramontozzi, LA and Connor,
KM and Lindahl, VH and Massie, RW},
Title = {ECT stimulus intensity: are present ECT devices too
limited?},
Journal = {The American Journal of Psychiatry},
Volume = {157},
Number = {6},
Pages = {963-967},
Year = {2000},
Month = {June},
ISSN = {0002-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10831477},
Keywords = {Brain • Depressive Disorder • Electric Stimulation
• Electroconvulsive Therapy • Electroencephalography
• Female • Functional Laterality • Humans
• Male • Mental Disorders • Middle Aged
• Multivariate Analysis • Regression Analysis
• Retrospective Studies • Schizophrenia •
Schizophrenic Psychology • Treatment Outcome •
instrumentation • methods* • physiology •
psychology • statistics & numerical data •
statistics & numerical data* • therapy •
therapy*},
Abstract = {OBJECTIVE: The maximum output charge for ECT devices is
limited to 576 millicoulombs in the United States, although
there are no data ensuring that this limit will allow
consistently effective treatments. The authors examined
whether this limit has a negative impact on therapeutic
response and, therefore, whether a higher stimulus charge
should be available. METHOD: They retrospectively reviewed
the records of 471 patients who received a clinical index
course of ECT at Duke University between 1991 and 1998.
These patients received conservative stimulus dosing of 2.25
times seizure threshold for unilateral ECT and 1.5 times
seizure threshold for bilateral ECT. RESULTS: Seventy-two
(15%) of the 471 patients required the maximum stimulus
intensity during their index ECT course. Of these, 24 (5% of
the total) had either a short EEG seizure (less than 25
seconds) or had no seizure at the maximum level. Strategies
to augment therapeutic response with caffeine, ketamine, or
hyperventilation were used in 14 of the 24 patients, and
data on therapeutic response were available for 22 of the
24. Only seven (32%) of these 22 patients were considered
ECT responders, compared with 242 (66%) of the remaining 364
patients for whom data on response to ECT were available.
Older age and pre-ECT course EEG slowing were predictors of
requiring the maximum stimulus level. CONCLUSIONS: The
maximum available stimulus output was therapeutically
insufficient for 5% of the patients studied even when
available means to augment response were instituted. This
percentage would likely be even larger with the use of a
less conservative dosing protocol for unilateral ECT.
Increases in maximum stimulus output for ECT devices should
be considered as a means to ensure adequate treatment
response.},
Language = {eng},
Doi = {10.1176/appi.ajp.157.6.963},
Key = {fds281987}
}
@article{fds311697,
Author = {Krystal, AD and Weiner, RD and Luber, B and Prudic, J and Devanand, DP and Sackeim, HA},
Title = {The role of the ictal EEG in ECT stimulus
dosing.},
Journal = {The Journal of Ect},
Volume = {16},
Number = {1},
Pages = {74-74},
Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
Year = {2000},
Month = {March},
ISSN = {1095-0680},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000085880600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311697}
}
@article{fds281976,
Author = {Zoldi, SM and Krystal, A and Greenside, HS},
Title = {Stationarity and redundancy of multichannel EEG data
recorded during generalized tonic-clonic
seizures.},
Journal = {Brain Topography},
Volume = {12},
Number = {3},
Pages = {187-200},
Year = {2000},
ISSN = {0896-0267},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10791682},
Keywords = {Aged • Electrodes • Electroencephalography* •
Epilepsy, Generalized • Female • Humans •
Male • Middle Aged • Models, Neurological* •
Reaction Time • Seizures • Signal Processing,
Computer-Assisted • diagnosis • diagnosis* •
physiology • physiopathology •
physiopathology*},
Abstract = {To improve our understanding of the physiology of
generalized tonic-clonic (GTC) seizures, we have
investigated the stationarity and redundancy of 21-electrode
EEG data recorded from ten patients during GTC seizures
elicited by electroconvulsive therapy (ECT). Stationarity
was examined by calculating probability density functions
(pdfs) and power spectra over small equal-length
non-overlapping time windows and then by studying, visually
and quantitatively, the evolution of these quantities over
the duration of the seizures. Our analysis shows that some
seizures had no demonstrable stationarity, that most
seizures had time intervals of at least a few seconds that
were statistically stationary by several criteria, and that,
in some seizures, there were leads which were delayed in
manifesting the statistical changes associated with seizure
onset evident in other leads. The redundancy analysis
demonstrated for the first time posterior-to-anterior time
delays in the mid-ictal region of GTC seizures. The
implications of these findings are discussed for the
analysis of GTC seizure EEG data, for the physiology of GTC
seizures, and for ECT research.},
Language = {eng},
Doi = {10.1023/a:1023489807177},
Key = {fds281976}
}
@article{fds281991,
Author = {Krystal, AD and West, M and Prado, R and Greenside, H and Zoldi, S and Weiner, RD},
Title = {EEG effects of ECT: implications for rTMS.},
Journal = {Depression and Anxiety},
Volume = {12},
Number = {3},
Pages = {157-165},
Year = {2000},
ISSN = {1091-4269},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11126190},
Keywords = {Brain Mapping • Cerebral Cortex • Depressive
Disorder, Major • Electroconvulsive Therapy* •
Electroencephalography* • Electromagnetic Fields*
• Evoked Potentials • Humans • physiology
• physiopathology • therapy*},
Abstract = {Electroconvulsive therapy (ECT) involves the use of
electrical stimulation to elicit a series of generalized
tonic-clonic seizures for therapeutic purposes and is the
most effective treatment known for major depression. These
treatments have significant neurophysiologic effects, many
of which are manifest in the electroencephalogram (EEG). The
relationship between EEG data and the response to ECT has
been studied since the 1940s, but for many years no
consistent correlates were found. Recent studies indicate
that a number of specific EEG features recorded during the
induced seizures (ictal EEG) as well as before and after a
course of treatment (interictal EEG) are related to both the
therapeutic efficacy and cognitive side effects. Similar to
ECT, repetitive transcranial magnetic stimulation (rTMS),
which involves focal electromagnetic stimulation of cortical
neurons, has also been studied as an antidepressant therapy
and also appears to have neurophysiologic effects, although
these have not been as fully investigated as is the case
with ECT. Given the similarity of these treatments, it is
natural to consider whether advances in understanding the
electrophysiologic correlates of the ECT response might have
implications for rTMS. The present article reviews the
literature on the EEG effects of ECT and discusses the
implications in terms of the likely efficacy and side
effects associated with rTMS in specific anatomic locations,
the potential for producing an antidepressant response with
rTMS without eliciting seizure activity, eliciting focal
seizures with rTMS, and the possibility of using rTMS to
focally modulate seizure induction and spread with ECT to
optimize treatment.},
Language = {eng},
Doi = {10.1002/1520-6394(2000)12:3<157::AID-DA7>3.0.CO;2-R},
Key = {fds281991}
}
@article{fds281883,
Author = {West, M and Prado, R and Krystal, AD},
Title = {Evaluation and Comparison of EEG Traces: Latent Structure in
Nonstationary Time Series},
Journal = {Journal of the American Statistical Association},
Volume = {94},
Number = {448},
Pages = {1083-1095},
Publisher = {Informa UK Limited},
Year = {1999},
Month = {December},
ISSN = {0162-1459},
url = {http://dx.doi.org/10.1080/01621459.1999.10473861},
Abstract = {We explore and illustrate the use of time series
decomposition methods for evaluating and comparing latent
structure in nonstationary electroencephalographic (EEG)
traces obtained from depressed patients during brain
seizures induced as part of electroconvulsive therapy (ECT).
Analysis of the patterns of change over time in the
frequency structure of such EEG data provides insight into
the neurophysiological mechanisms of action of this
effective but poorly understood antidepressant treatment,
and allows clinicians to modify ECT treatments to optimize
therapeutic benefits while minimizing associated side
effects. Our work has introduced new methods of
time-frequency analysis of EEG series that identify the
complete pattern of time evolution of frequency structure
over the course of a seizure, and usefully assist in these
scientific and clinical studies. New methods of
decomposition of flexible dynamic models provide time domain
decompositions of individual EEG series into collections of
latent components in different frequency bands. This allows
us to explore ECT seizure characteristics via inferences on
the time-varying parameters that characterize these latent
components, and to relate differences in such
characteristics across seizures to differences in the
therapeutic effectiveness and cognitive side effects of
those seizures. This article discusses the scientific
context and problems, development of nonstationary time
series models and new methods of decomposition to explore
time-frequency structure, and aspects of model fitting and
analysis. We include applied studies on two datasets from
recent clinical ECT studies. One is an initial illustrative
analysis of a single EEG trace, the second compares the EEG
data recorded during two types of ECT treatment that differ
in therapeutic effectiveness and cognitive side effects. The
uses of these models and time series decomposition methods
in extracting and contrasting key features of the seizure
underlying the EEG signals are highlighted. Through the use
of these models we have quantified, for the first time,
decreases in the dominant frequencies of low-frequency EEG
components during ECT seizures. We have also identified
preliminary evidence that such decreases are enhanced under
the more effective ECTs at higher electrical dosages, a
finding consistent with prior reports and the hypothesis
that more effective forms of ECT are more effective in
eliciting neurophysiological inhibitory processes. © 1999
Taylor & Francis Group, LLC.},
Doi = {10.1080/01621459.1999.10473861},
Key = {fds281883}
}
@article{fds281998,
Author = {Krystal, AD and Prado, R and West, M},
Title = {New methods of time series analysis of non-stationary EEG
data: eigenstructure decompositions of time varying
autoregressions.},
Journal = {Clinical Neurophysiology : Official Journal of the
International Federation of Clinical Neurophysiology},
Volume = {110},
Number = {12},
Pages = {2197-2206},
Year = {1999},
Month = {December},
ISSN = {1388-2457},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10616127},
Keywords = {Brain • Electroencephalography* • Humans •
Models, Neurological • Regression Analysis • Time
Factors • physiology*},
Abstract = {OBJECTIVE: Those who analyze EEG data require quantitative
techniques that can be validly applied to time series
exhibiting ranges of non-stationary behavior. Our objective
is to introduce a new analysis technique based on formal
non-stationary time series models. This novel method
provides a decomposition of the time series into a set of
'latent' components with time-varying frequency content. The
identification of these components can lead to practical
insights and quantitative comparisons of changes in
frequency structure over time in EEG time series. METHODS:
The technique begins with the development of time-varying
autoregressive models of the EEG time series. Such models
have been previously used in EEG analysis but we extend
their utility by the introduction of eigenstructure
decomposition methods. We review the basis and
implementation of this method and report on the analysis of
two channel EEG data recorded during 3 generalized
tonic-clonic seizures induced in an individual as part of a
course of electroconvulsive therapy for major depression.
RESULTS: This technique identified EEG patterns consistent
with prior reports. In addition, it quantified a decrease in
dominant frequency content over the seizures and suggested
for the first time that this decrease is continuous across
the end of the seizures. The analysis also suggested that
the seizure EEG may be best modeled by the combination of
multiple processes, whereas post-ictally there appears to be
one dominant process. There was also preliminary evidence
that these features may differ as a function of ECT
therapeutic effectiveness. CONCLUSIONS: Eigenanalysis of
time-varying autoregressive models has promise for improving
the analysis of EEG time series.},
Language = {eng},
Doi = {10.1016/s1388-2457(99)00165-0},
Key = {fds281998}
}
@article{fds281977,
Author = {Asnis, GM and Chakraburtty, A and DuBoff, EA and Krystal, A and Londborg, PD and Rosenberg, R and Roth-Schechter, B and Scharf, MB and Walsh, JK},
Title = {Zolpidem for persistent insomnia in SSRI-treated depressed
patients.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {60},
Number = {10},
Pages = {668-676},
Year = {1999},
Month = {October},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10549683},
Keywords = {Adult • Comorbidity • Depressive Disorder •
Double-Blind Method • Drug Therapy, Combination •
Female • Follow-Up Studies • Humans •
Hypnotics and Sedatives • Male • Placebos •
Pyridines • Serotonin Uptake Inhibitors •
Single-Blind Method • Sleep • Sleep Initiation and
Maintenance Disorders • Treatment Outcome •
adverse effects* • chemically induced* • drug
effects • drug therapy* • epidemiology •
pharmacology • therapeutic use*},
Abstract = {BACKGROUND: Depressed individuals effectively treated with
selective serotonin reuptake inhibitors (SSRIs) often report
persistent insomnia and require adjunctive sleep-promoting
therapy. METHOD: Men (N = 40) and women (N = 150) with a
mean age of 41.6 years who had persistent insomnia in the
presence of effective and stable treatment (at least 2
weeks) with fluoxetine (< or =40 mg/day), sertraline (< or
=100 mg/day), or paroxetine (< or =40 mg/day) for DSM-IV
major depressive disorder, dysthymic disorder, or minor
depressive disorder of mild-to-moderate severity (and score
of < or =2 on item 3 of the Hamilton Rating Scale for
Depression [HAM-D]) participated in this randomized,
double-blind, parallel-group study. At study entry, patients
were required to score < or =12 on the HAM-D. During a
1-week single-blind placebo period, patients had to report
on at least 3 nights a latency of > or =30 minutes or a
sleep time of <6.5 hours and clinically significant daytime
impairment. Patients received either placebo (N = 96) or
zolpidem, 10 mg (N = 94) nightly, for 4 weeks and
single-blind placebo for 1 week thereafter. Sleep was
measured with daily questionnaires and during weekly
physician visits. RESULTS: Compared with placebo, zolpidem
was associated with improved sleep: longer sleep times
(weeks 1 through 4, p<.05), greater sleep quality (weeks 1
through 4, p<.01), and reduced number of awakenings (weeks
1, 2, and 4; p<.05), together with feeling significantly
more refreshed, less sleepy, and more able to concentrate.
After placebo substitution, the zolpidem group showed
significant worsening relative to pretreatment sleep on the
first posttreatment night in total sleep time and sleep
quality, reverted to pretreatment insomnia levels on the
other hypnotic efficacy measures, or maintained improvement
(fewer number of awakenings). There was no evidence of
dependence or withdrawal from zolpidem (DSM-IV criteria).
Incidence rates of adverse events were similar in both
treatment groups (74% and 83% for placebo and zolpidem,
respectively), but 7 zolpidem patients discontinued compared
with 2 placebo patients. CONCLUSION: In this defined patient
population, zolpidem, 10 mg, was effectively and safely
co-administered with an SSRI, resulting in improved
self-rated sleep, daytime functioning, and
well-being.},
Language = {eng},
Doi = {10.4088/jcp.v60n1005},
Key = {fds281977}
}
@article{fds281882,
Author = {West, M and Prado, R and Krystal, AD},
Title = {Evaluation and Comparison of EEG Traces: Latent Structure in
Nonstationary Time Series},
Journal = {Journal of the American Statistical Association},
Volume = {94},
Number = {446},
Pages = {375-387},
Publisher = {Informa UK Limited},
Year = {1999},
Month = {June},
ISSN = {0162-1459},
url = {http://dx.doi.org/10.1080/01621459.1999.10474128},
Abstract = {We explore and illustrate the use of time series
decomposition methods for evaluating and comparing latent
structure in nonstationary electroencephalographic (EEG)
traces obtained from depressed patients during brain
seizures induced as part of electroconvulsive therapy (ECT).
Analysis of the patterns of change over time in the
frequency structure of such EEG data provides insight into
the neurophysiological mechanisms of action of this
effective but poorly understood antidepressant treatment,
and allows clinicians to modify ECT treatments to optimize
therapeutic benefits while minimizing associated side
effects. Our work has introduced new methods of
time-frequency analysis of EEG series that identify the
complete pattern of time evolution of frequency structure
over the course of a seizure, and usefully assist in these
scientific and clinical studies. New methods of
decomposition of flexible dynamic models provide time domain
decompositions of individual EEG series into collections of
latent components in different frequency bands. This allows
us to explore ECT seizure characteristics via inferences on
the time-varying parameters that characterize these latent
components, and to relate differences in such
characteristics across seizures to differences in the
therapeutic effectiveness and cognitive side effects of
those seizures. This article discusses the scientific
context and problems, development of nonstationary time
series models and new methods of decomposition to explore
time-frequency structure, and aspects of model fitting and
analysis. We include applied studies on two datasets from
recent clinical ECT studies. One is an initial illustrative
analysis of a single EEG trace, the second compares the EEG
data recorded during two types of ECT treatment that differ
in therapeutic effectiveness and cognitive side effects. The
uses of these models and time series decomposition methods
in extracting and contrasting key features of the seizure
underlying the EEG signals are highlighted. Through the use
of these models we have quantified, for the first time,
decreases in the dominant frequencies of low-frequency EEG
components during ECT seizures. We have also identified
preliminary evidence that such decreases are enhanced under
the more effective ECTs at higher electrical dosages, a
finding consistent with prior reports and the hypothesis
that more effective forms of ECT are more effective in
eliciting neurophysiological inhibitory processes. © 1999
Taylor & Francis Group, LLC.},
Doi = {10.1080/01621459.1999.10474128},
Key = {fds281882}
}
@article{fds281986,
Author = {Krystal, AD and Weiner, RD},
Title = {EEG correlates of the response to ECT: a possible
antidepressant role of brain-derived neurotrophic
factor.},
Journal = {The Journal of Ect},
Volume = {15},
Number = {1},
Pages = {27-38},
Year = {1999},
Month = {March},
ISSN = {1095-0680},
url = {http://www.ncbi.nlm.nih.gov/pubmed/10189617},
Keywords = {Depressive Disorder • Electroconvulsive Therapy* •
Electroencephalography • Humans • Nerve Growth
Factors • Nerve Tissue Proteins • Prefrontal
Cortex • pharmacology* • physiology* •
therapy*},
Abstract = {Studies on the relationship of electroencephalographic (EEG)
data to the therapeutic response to electroconvulsive
therapy (ECT) have been carried out since the 1940s, but for
many years they did not yield any consistent correlates.
Recent studies, however, are providing a growing body of
evidence of relationships between the antidepressant
response to ECT and both the ictal (recorded during ECT
seizures) and interictal (recorded during waking) EEG. These
studies appear to be consistent in pointing to the
importance of electrophysiologic changes in the prefrontal
cortex as a potential mediator of the antidepressant
response to ECT. The available findings are reviewed and
discussed in light of recent neurophysiologic and
neuropsychiatric research, including that related to
neurotrophic factors.},
Language = {eng},
Key = {fds281986}
}
@article{fds311670,
Author = {Weiner, RD and Krystal, AD},
Title = {2. ECT and Anticonvulsant Medications},
Journal = {The Journal of Ect},
Volume = {15},
Number = {1},
Pages = {104-104},
Publisher = {Ovid Technologies (Wolters Kluwer Health)},
Year = {1999},
Month = {March},
ISSN = {1095-0680},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000084423100014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Doi = {10.1097/00124509-199903000-00014},
Key = {fds311670}
}
@article{fds311698,
Author = {Krystal, AD and Weiner, RD and R. Krishnan and KR},
Title = {3. Magnetic Resonance Spectroscopic Correlates of the
Response to ECT},
Journal = {The Journal of Ect},
Volume = {15},
Number = {1},
Pages = {103-103},
Publisher = {Ovid Technologies (Wolters Kluwer Health)},
Year = {1999},
Month = {March},
ISSN = {1095-0680},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000084423100011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Doi = {10.1097/00124509-199903000-00011},
Key = {fds311698}
}
@article{fds135982,
Title = {West, M. Prado, R. and Krystal, A. Evaluation and
comparison of EEG traces: Latent structure in non-staionary
time series. Journal of the American Statistical
Association, 94:375-387, 1999.},
Year = {1999},
Key = {fds135982}
}
@article{fds281967,
Author = {Krystal, AD and Edinger, J and Wohlgemuth, W and Marsh,
GR},
Title = {Sleep in peri-menopausal and post-menopausal
women.},
Journal = {Sleep Medicine Reviews},
Volume = {2},
Number = {4},
Pages = {243-253},
Year = {1998},
Month = {November},
ISSN = {1087-0792},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15310495},
Abstract = {Despite the fact that a large number of women report sleep
disturbances associated with peri-menopausal and
post-menopausal periods, there is a surprising lack of
literature related to this issue. In fact, there has not
been enough work in this area to even definitively establish
whether there is a sleep disorder that is specifically
related to these life-stage changes. Herein we review the
available literature which suggests that insomnia may be
directly linked to the changes that occur during the
peri/post-menopausal periods. This insomnia appears to be
due to night sweats caused by the hormonal changes which
occur and which lead to an increase in arousals. Persistence
of insomnia symptoms after adequate hormone replacement
therapy may indicate that behavioral conditioning of the
insomnia initially triggered by the night sweats may have
occurred. Alternatively, such an insomnia in a
peri/post-menopausal woman could be due to unresolved grief
related to going through menopause or could reflect an
independent sleep disorder, such as periodic movements of
sleep, sleep apnea, depression, anxiety, etc. Whereas
menopausal changes do not directly lead to an increase in
sleep apnea they seemingly contribute to an increased risk
for this disorder. In view of these considerations, we
provide guidelines for the proper diagnosis and treatment of
peri/post-menopausal women with sleep complaints.},
Doi = {10.1016/s1087-0792(98)90011-9},
Key = {fds281967}
}
@article{fds281959,
Author = {Krystal, AD and Greenside, HS and Gottschalk, A and Bauer, MS and Whybrow, PC},
Title = {Low-dimensional chaos in bipolar disorder [1] (multiple
letters)},
Journal = {Archives of Internal Medicine},
Volume = {158},
Number = {5},
Pages = {275},
Year = {1998},
Month = {March},
ISSN = {0003-990X},
url = {http://dx.doi.org/10.1001/archpsyc.55.3.275},
Doi = {10.1001/archpsyc.55.3.275},
Key = {fds281959}
}
@article{fds281984,
Author = {Krystal, AD and Greenside, HS},
Title = {Low-dimensional chaos in bipolar disorder?},
Journal = {Archives of General Psychiatry},
Volume = {55},
Number = {3},
Pages = {275-276},
Year = {1998},
Month = {March},
ISSN = {0003-990X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/9510223},
Keywords = {Affect* • Bipolar Disorder • Fractals •
Humans • Models, Statistical • Nonlinear Dynamics*
• Stochastic Processes • diagnosis* •
psychology},
Language = {eng},
Doi = {10.1001/archpsyc.55.3.275},
Key = {fds281984}
}
@article{fds282009,
Author = {Krystal, AD and Watts, BV and Weiner, RD and Moore, S and Steffens, DC and Lindahl, V},
Title = {The use of flumazenil in the anxious and
benzodiazepine-dependent ECT patient.},
Journal = {The Journal of Ect},
Volume = {14},
Number = {1},
Pages = {5-14},
Year = {1998},
Month = {March},
ISSN = {1095-0680},
url = {http://www.ncbi.nlm.nih.gov/pubmed/9661088},
Keywords = {Adult • Aged • Anti-Anxiety Agents* • Anxiety
Disorders • Arousal • Depressive Disorder •
Electroconvulsive Therapy* • Electroencephalography
• Female • Flumazenil • GABA Modulators
• Humans • Male • Middle Aged •
Premedication • Retrospective Studies • Substance
Withdrawal Syndrome • Substance-Related Disorders
• Treatment Outcome • administration & dosage
• administration & dosage* • adverse effects
• drug effects • etiology* • psychology
• rehabilitation*},
Abstract = {Many patients who receive electroconvulsive therapy (ECT)
are benzodiazepine dependent or are anxious and require
benzodiazepine drugs. Because these agents may diminish the
therapeutic effectiveness of ECT, we explored the dosing,
safety, and efficacy of pre-ECT flumazenil administration, a
benzodiazepine-competitive antagonist, in patients receiving
benzodiazepine medications. We report our experience with 35
patients who received both flumazenil and benzodiazepine
drugs during their ECT course. We compared seizure duration
with and without flumazenil and compared treatment efficacy
to 49 patients who received ECT without either of these
medications. Flumazenil could be safely administered with
ECT. A few subjects taking higher chronic benzodiazepine
dosages experienced breakthrough anxiety or withdrawal
symptoms, which were well managed by dosing flumazenil
immediately before the anesthetic agent and by immediate
posttreatment benzodiazepine administration. A dose of
0.4-0.5 mg was adequate for all but those taking the highest
benzodiazepine dosages, where 0.8-1.0 mg resulted in a
clinically more effective reversal. No differences in
efficacy or seizure duration were found as a function of
flumazenil administration. Flumazenil offers the promise of
safe and effective ECT in patients receiving benzodiazepine
drugs. Follow-up outcome investigation on a random
assignment basis will be necessary for definitive assessment
of the value of flumazenil. In addition, the direct effect
of benzodiazepine drugs and the flumazenil/benzodiazepine
combination on ECT seizures remains to be
determined.},
Language = {eng},
Key = {fds282009}
}
@article{fds281968,
Author = {Krystal, AD},
Title = {The clinical utility of ictal EEG seizure adequacy
models},
Journal = {Psychiatric Annals},
Volume = {28},
Number = {1},
Pages = {30-35},
Publisher = {SLACK INC},
Year = {1998},
Month = {January},
url = {http://dx.doi.org/10.3928/0048-5713-19980101-08},
Doi = {10.3928/0048-5713-19980101-08},
Key = {fds281968}
}
@article{fds135968,
Title = {Krystal, A.D., (member of the U.S. Modafinil in Narcolepsy
Study Group). HLA-DQB1*0602 homozygosity increases relative
risk for narcolepsy but not disease severity in two ethnic
groups. Tissue Antigens 51:96-100, 1998.},
Year = {1998},
Key = {fds135968}
}
@article{fds135969,
Title = {Weiner, R.D., Krystal, A.D. The cognitive side-effects of
ECT. Progress in Neuro- Psychopharmacology & Biological
Psychiatry, in press.},
Year = {1998},
Key = {fds135969}
}
@article{fds136000,
Title = {Krystal AD. The clinical utility of ictal EEG seizure
adequacy models. Psychiatric Annals 1:30- 35,
1998.},
Year = {1998},
Key = {fds136000}
}
@article{fds136001,
Title = {Krystal, A.D., (member of the U.S. Modafinil in Narcolepsy
Study Group). Randomized trial of modafinil for the
treatment of pathological somnolence in narcolepsy. Annals
of Neurology 43:88-97, 1998.},
Year = {1998},
Key = {fds136001}
}
@article{fds136002,
Title = {Krystal, A.D., Edinger, J., Wohlgemuth, W., Marsh, G.R.
Sleep in peri-menopausal and post- menopausal women. Sleep
Medicine Reviews, 2:243-253, 1998.},
Year = {1998},
Key = {fds136002}
}
@article{fds136003,
Title = {West, M., Prado, R., Krystal, A.D. Evaluation and comparison
of EEG traces: Latent structure in non-stationary time
series. Journal of the American Statistical Association, in
press.},
Year = {1998},
Key = {fds136003}
}
@article{fds136004,
Title = {Krystal, A.D., Zoldi, S., Greenside, H., Prado, R., West,
M., Weiner, R. The effects of ECT on the EEG: implicatons
for rTMS. Progress in Neuro-Psychopharmacology & Biological
Psychiatry, in press.},
Year = {1998},
Key = {fds136004}
}
@article{fds136005,
Title = {Weiner RD, Coffey CE and Krystal AD. Electroconvulsive
therapy in the medical and neurological patient. 2nd
edition. IN: Psychiatric Care of the Medical Patient.
(Stoudemire A, Fogel BS, Eds.), New York, Oxford University
Press, in press.},
Year = {1998},
Key = {fds136005}
}
@article{fds136006,
Title = {Krystal, A.D., Zoldi, S., Prado, R., Greenside, H.S., West,
M. The spatiotemporal dynamics of generalized tonic-clonic
seizure EEG data: Relevance to the clinical practice of
electroconvulsive therapy. IN: Proceedings of the
International Conference on Nonlinear Dynamics and Brain
Functioning (Rapp, P., Ed.). In Press.},
Year = {1998},
Key = {fds136006}
}
@article{fds281980,
Author = {Krystal, AD and Coffey, CE and Weiner, RD and Holsinger,
T},
Title = {Changes in seizure threshold over the course of
electroconvulsive therapy affect therapeutic response and
are detected by ictal EEG ratings.},
Journal = {The Journal of Neuropsychiatry and Clinical
Neurosciences},
Volume = {10},
Number = {2},
Pages = {178-186},
Year = {1998},
ISSN = {0895-0172},
url = {http://www.ncbi.nlm.nih.gov/pubmed/9608406},
Keywords = {Aged • Cerebral Cortex • Chi-Square Distribution
• Depressive Disorder • Differential Threshold
• Disease Susceptibility • Electroconvulsive
Therapy* • Electroencephalography* • Factor
Analysis, Statistical • Female • Humans •
Male • Middle Aged • Models, Neurological •
Multivariate Analysis • Regression Analysis •
Seizures • Sensitivity and Specificity • Treatment
Outcome • etiology* • physiology •
physiopathology • therapy*},
Abstract = {Therapeutic effectiveness of electroconvulsive therapy is
influenced by the degree to which the stimulus intensity
exceeds the seizure threshold. However, the threshold rises
variably over the treatment course, confounding maintenance
of desired relative stimulus intensity. In 47 depressed
patients, decreases in relative stimulus intensity between
treatments 1 and 6 were associated with diminished
therapeutic response at treatment 6 for unilateral (UL) ECT.
A multivariate model including manual ratings of ictal EEG
data predicted whether seizure threshold rose with 82%
accuracy. The same EEG variables were also significantly
related to therapeutic response. Thus, decreases in relative
stimulus intensity over the ECT course affect the
therapeutic potency of UL ECT. Further, ictal EEG indices
have considerable potential for predicting such stimulus
intensity changes and their effect on therapeutic
outcome.},
Language = {eng},
Doi = {10.1176/jnp.10.2.178},
Key = {fds281980}
}
@article{fds281989,
Author = {Krystal, AD and Zaidman, C and Greenside, HS and Weiner, RD and Coffey,
CE},
Title = {The largest Lyapunov exponent of the EEG during ECT seizures
as a measure of ECT seizure adequacy.},
Journal = {Electroencephalography and Clinical Neurophysiology},
Volume = {103},
Number = {6},
Pages = {599-606},
Year = {1997},
Month = {December},
ISSN = {0013-4694},
url = {http://www.ncbi.nlm.nih.gov/pubmed/9546486},
Keywords = {Adult • Aged • Depression • Electroconvulsive
Therapy • Electroencephalography • Humans •
Middle Aged • Reproducibility of Results •
Treatment Outcome • methods* • standards* •
therapy*},
Abstract = {Attributes of the electroencephalogram (EEG) recorded during
electroconvulsive therapy (ECT) seizures appear promising
for decreasing the uncertainty that exists about how to
define a therapeutically adequate seizure. In the present
report we study whether one promising and not yet tested
ictal EEG measure, the largest Lyapunov exponent (lambda1),
is useful in this regard. We calculated lambda1 from 2
channel ictal EEG data recorded in 25 depressed subjects who
received right unilateral ECT. We studied the relationship
of lambda1 to treatment therapeutic outcome and to an
indirect measure of treatment therapeutic potency, the
extent to which the stimulus intensity exceeds the seizure
threshold. We found lambda1 could be reliably calculated
from ictal EEG data and that the global mean, maximum, and
standard deviation of lambda1 were smaller in the more
therapeutically potent moderately suprathreshold ECT and in
therapeutic responders. These results imply a more
predictable or consistent pattern of EEG seizure activity
over time in more therapeutically effective ECT seizures.
These findings also suggest the promise of lambda1 as a
marker of ECT seizure therapeutic adequacy and build on our
previous work suggesting that lambda1 may be useful for
classifying seizures and for reflecting the relative
physiologic impact of seizure activity.},
Language = {eng},
Doi = {10.1016/s0013-4694(97)00062-x},
Key = {fds281989}
}
@article{fds311669,
Author = {Krystal, AD and Coffey, CE and Weiner, RD and Rapp, PE and Albano, A and Greenside, HS and DeMasi, M and Cellucci, C},
Title = {EEG correlates of the response to ECT},
Journal = {Biological Psychiatry},
Volume = {41},
Pages = {189-189},
Publisher = {ELSEVIER SCIENCE INC},
Year = {1997},
Month = {April},
ISSN = {0006-3223},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1997WQ70900192&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311669}
}
@article{fds319933,
Author = {Krystal, AD and Weiner, RD and Watts, BV and Moore, S and Steffens, DC and Lindahl, V},
Title = {The use of flumazenil in the anxious and
benzodiazepine-dependent ECT patient.},
Journal = {Convulsive Therapy},
Volume = {13},
Number = {1},
Pages = {57-58},
Publisher = {LIPPINCOTT-RAVEN PUBL},
Year = {1997},
Month = {March},
Key = {fds319933}
}
@article{fds311695,
Author = {Weiner, RD and Krystal, AD and Steffens, DC},
Title = {Establishing an ambulatory ECT program: Different
models.},
Journal = {Convulsive Therapy},
Volume = {13},
Number = {1},
Pages = {49-49},
Publisher = {LIPPINCOTT-RAVEN PUBL},
Year = {1997},
Month = {March},
ISSN = {0749-8055},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1997WY15700013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311695}
}
@article{fds135965,
Title = {Krystal, A.D., Watts, B.V., Weiner, R.D., Moore, S.,
Steffens, D., Lindahl, V. The use of flumazenil in the
anxious and benzodiazepine dependent ECT patient. Convulsive
Therapy 13(4)xx-xx, 1997.},
Year = {1997},
Key = {fds135965}
}
@article{fds135966,
Title = {Edinger, J.D., Fins, A.I., Goeke, J.M., McMillan, D.K.,
Gersh, T.L., Krystal, A.D., McCall, W.V. The empirical
identification of insomnia subtypes: A cluster analytic
approach. Sleep (in press).},
Year = {1997},
Key = {fds135966}
}
@article{fds135967,
Title = {Krystal, A.D., Weiner, R.D., Lindahl, V, Massie, R. Dosing
ECT treatments on the basis of the ictal EEG: A preliminary
study.},
Year = {1997},
Key = {fds135967}
}
@article{fds135993,
Title = {Krystal, A.D., Zaidman, C., Greenside, H.S., Weiner, R.D.,
Coffey, C.E. The largest Lyapunov exponent of the EEG during
ECT seizures as a measure of therapeutic adequacy.
Electroencephalography and Clinical Neurophysiology
103:599-606, 1997.},
Year = {1997},
Key = {fds135993}
}
@article{fds135994,
Title = {Krystal, A.D., Coffey, C.E. Neuropsychiatric considerations
in the use of Electroconvulsive Therapy. Journal of
Neuropsychiatry and Clinical Neurosciences 9:283-292,
1997.},
Year = {1997},
Key = {fds135994}
}
@article{fds135995,
Title = {Krystal, A.D. The clinical utility of ictal EEG seizure
adequacy models. Psychiatric Annals, 1:30-35,
1998.},
Year = {1997},
Key = {fds135995}
}
@article{fds135996,
Title = {Krystal, A.D., Greenside, H.S. Low Dimensional Chaos in
Bipolar Disorders? (Letter to the Editor) Arch. Gen.
Psychiatry (in press).},
Year = {1997},
Key = {fds135996}
}
@article{fds135997,
Title = {Krystal, A.D., Coffey, C.E., Weiner, R.D., Holsinger, T.
Changes in seizure threshold over the ECT course affect
therapeutic response and are detected by ictal EEG ratings.
J. Neuropsychiatry & Clin. Neurosci. in press.},
Year = {1997},
Key = {fds135997}
}
@article{fds135998,
Title = {Krystal, A.D., Weiner, R.D. EEG Correlates of the response
to ECT: A possible antidepressant role of brain derived
neurotrophic factor, Journal of ECT.},
Year = {1997},
Key = {fds135998}
}
@article{fds135999,
Title = {Krystal, A.D., Holsinger, T., Weiner, R.D., Coffey, C.E.,
Predicting unilateral ECT response and the utility of a
switch to bilateral ECT with treatment 2 ictal EEG
indices.},
Year = {1997},
Key = {fds135999}
}
@article{fds282000,
Author = {Krystal, AD and Coffey, CE},
Title = {Neuropsychiatric considerations in the use of
electroconvulsive therapy.},
Journal = {The Journal of Neuropsychiatry and Clinical
Neurosciences},
Volume = {9},
Number = {2},
Pages = {283-292},
Year = {1997},
ISSN = {0895-0172},
url = {http://www.ncbi.nlm.nih.gov/pubmed/9144111},
Keywords = {Brain Diseases • Electroconvulsive Therapy* •
Humans • therapy*},
Abstract = {ECT is an effective and rapidly acting treatment for certain
major psychiatric disorders, even in patients with
neurologic illness. Further, in some cases the neurologic
illness itself also responds to ECT. Patients with some
types of neurologic illness may be at increased risk of
neurologic or cognitive side effects from ECT, but these
risks can be lowered by careful pre-ECT evaluation and
optimal ECT technique.},
Language = {eng},
Doi = {10.1176/jnp.9.2.283},
Key = {fds282000}
}
@article{fds311691,
Author = {Zoldi, SM and Krystal, AD and Greenside, HS},
Title = {Statistical analysis of redundancy and stationarity in
multi-channel EEG.},
Journal = {Journal of Mathematical Psychology},
Volume = {40},
Number = {4},
Pages = {354-355},
Publisher = {ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS},
Year = {1996},
Month = {December},
ISSN = {0022-2496},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1996WD68400032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311691}
}
@article{fds281999,
Author = {Krystal, AD and Greenside, HS and Weiner, RD and Gassert,
D},
Title = {A comparison of EEG signal dynamics in waking, after
anesthesia induction and during electroconvulsive therapy
seizures.},
Journal = {Electroencephalography and Clinical Neurophysiology},
Volume = {99},
Number = {2},
Pages = {129-140},
Year = {1996},
Month = {August},
ISSN = {0013-4694},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8761049},
Keywords = {Adult • Aged • Brain • Depressive Disorder
• Electroconvulsive Therapy • Electroencephalography
• Humans • Male • Middle Aged • Seizures
• Wakefulness • physiology* •
physiopathology*},
Abstract = {Evidence suggests that quantitative dynamical measures of
electroencephalogram (EEG) signals are more appropriate for
characterizing the differences between states in an
individual rather than as absolute indices. One such
measure, the largest Lyapunov exponent (lambda 1), appears
to have potential for identifying seizure activity and for
being of clinical utility for characterizing
electroconvulsive therapy (ECT) seizures. As a result, we
compared lambda 1 for the EEG recorded in 8 depressed
subjects in 3 states: (1) during right unilateral ECT
seizures, (2) during the pre-ECT waking state, and (3)
following anesthesia administration but prior to ECT.
Spectral amplitude and autocorrelation were also calculated
in these states, allowing a comparison of these measures
with lambda 1. We hypothesized that lambda 1 would be lowest
during the ECT seizures, suggestive of greater EEG signal
predictability over time during the seizures. We found that
during the seizures lambda 1 was smaller, while spectral
amplitude was larger. Significant inter-state differences
were not found for the left temporal and occipital regions
suggesting that these measures might serve as markers of the
degree of seizure involvement of specific brain regions.
Spectral amplitude and lambda 1 were uncorrelated and varied
independently in some cases. The autocorrelation time was
shortest in the waking EEG, and longest for the
post-anesthesia EEG, and did not account for the differences
seen in lambda 1. In contrast, the persistence of
oscillations in the autocorrelation functions was greater
for the ictal EEG than the other two states and may relate
to lambda 1.},
Language = {eng},
Doi = {10.1016/0013-4694(96)95090-7},
Key = {fds281999}
}
@article{fds282006,
Author = {Edinger, JD and Fins, AI and Goeke, JM and McMillan, DK and Gersh, TL and Krystal, AD and McCall, WV},
Title = {The empirical identification of insomnia subtypes: a cluster
analytic approach.},
Journal = {Sleep},
Volume = {19},
Number = {5},
Pages = {398-411},
Year = {1996},
Month = {June},
ISSN = {0161-8105},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8843531},
Keywords = {Adult • Cluster Analysis • Female • Humans
• Male • Middle Aged • Polysomnography •
Psychiatric Status Rating Scales • Sleep Initiation and
Maintenance Disorders • diagnosis*},
Abstract = {Over the past 15 years, there has been considerable debate
concerning the extent to which insomnia patients can be
classified into diagnostic subtypes. Despite this debate,
relatively little research has been conducted to empirically
determine whether naturally occurring insomnia subtypes
might be identified within populations of sleep clinic
patients. In the current study we used a hierarchical
cluster analysis to empirically identify subtypes among a
mixed group of normal sleepers and the insomnia outpatients
who presented to our sleep center over the past decade.
Using factor-analytically derived composite variables that
summarized data obtained from sleep history questionnaires
and polysomnographic monitoring, this clustering procedure
resulted in the identification of 14 subgroups that varied
between four and 34 patients/subjects in size. Subsequently,
subgroup mean scores for the composite variables used in the
clustering procedure were used to construct profiles for
each of the 14 clusters. A multivariate profile analysis,
employed to elucidate subgroup differences, showed that
these cluster profiles differed in terms of their configural
shapes, average elevations, and degrees of interscale
differences. Furthermore, both DSM-III-R (American
Psychiatric Association) and International Classification of
Sleep Disorders (ICSD) insomnia diagnoses, assigned
independent of cluster findings, suggested that these
subtypes differed significantly in regard to their
diagnostic compositions. Nevertheless, a far-from-perfect
concordance was observed between such clinically assigned
diagnoses and cluster group membership. In fact, many of the
empirically identified groups were composed of various
DSM-III-R and/or ICSD diagnostic subtypes. These results
provided only partial support for current DSM and ICSD
insomnia categories. However, our results support the
existence of multiple, clinically discrete insomnia subtypes
and provide information that may be useful in future
revisions of current insomnia nosologies.},
Language = {eng},
Key = {fds282006}
}
@article{fds281982,
Author = {Krystal, AD and Weiner, RD and Coffey, CE and McCall,
WV},
Title = {Effect of ECT treatment number on the ictal
EEG.},
Journal = {Psychiatry Research},
Volume = {62},
Number = {2},
Pages = {179-189},
Year = {1996},
Month = {May},
ISSN = {0165-1781},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8771615},
Keywords = {Adult • Aged • Cerebral Cortex • Depressive
Disorder • Dominance, Cerebral • Electroconvulsive
Therapy • Electroencephalography* • Evoked
Potentials • Female • Humans • Male •
Middle Aged • Prognosis • Psychotic Disorders
• Schizophrenia • Schizophrenic Psychology •
Treatment Outcome • methods* • physiology •
physiopathology • psychology •
therapy*},
Abstract = {Recent evidence suggests that attributes of the ictal
electroencephalogram (EEG) may be clinically useful for
estimating the extent to which the electroconvulsive therapy
(ECT) stimulus exceeds the seizure threshold (relative
stimulus intensity). Such a tool could allow a practitioner,
who chose, on the basis of expected therapeutic response and
side effect rates, to implement stimulus dosing to maintain
relative stimulus intensity over the treatment course,
despite the uncertain rise in seizure threshold that occurs.
One potential confounding factor is a possible systematic
change in the ictal EEG over the treatment course that is
not due to changes in seizure threshold. We explored the
effect of treatment number by comparing ictal EEG data
obtained at treatments across the ECT course that were
delivered at the identical relative stimulus intensity. We
found that the ictal EEG at treatment 1 was characterized by
a greater mid-ictal amplitude and post-ictal suppression
(trend) than subsequent treatments for barely suprathreshold
unilateral ECT, but not for barely suprathreshold bilateral
or moderately suprathreshold unilateral ECT, and that this
change may affect therapeutic effectiveness. These findings
suggest the importance of treatment-number effects for the
clinical application of the ictal EEG and point to possible
physiological differences between unilateral and bilateral
ECT.},
Language = {eng},
Doi = {10.1016/0165-1781(96)02844-2},
Key = {fds281982}
}
@article{fds281990,
Author = {Krystal, AD and Weiner, RD and Gassert, D and McCall, WV and Coffey, CE and Sibert, T and Holsinger, T},
Title = {The relative ability of three ictal EEG frequency bands to
differentiate ECT seizures on the basis of electrode
placement, stimulus intensity, and therapeutic
response.},
Journal = {Convulsive Therapy},
Volume = {12},
Number = {1},
Pages = {13-24},
Year = {1996},
Month = {March},
ISSN = {0749-8055},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8777648},
Keywords = {Algorithms • Analysis of Variance • Depressive
Disorder • Dose-Response Relationship, Radiation •
Electroconvulsive Therapy* • Electrodes •
Electroencephalography* • Female • Humans •
Male • Middle Aged • Psychiatric Status Rating
Scales • psychology • therapy*},
Abstract = {Ictal EEG indices show promise for separating individual ECT
seizures on the basis of treatment electrode placement
(ELPL), relative stimulus intensity (Dose), and expected
therapeutic response. One factor impeding the effective
clinical implementation of ictal EEG indices for these
purposes is uncertainty as to the relative utility of lower
and higher frequency EEG activity. Recent articles are
contradictory in this regard, but no data exist addressing
this issue. As a result, we reanalyzed data from 44 subjects
in two studies and compared the relative ability of ictal
EEG data in three frequency bands to differentiate seizures
as a function of ELPL, Dose, and therapeutic response. We
found that the frequency band that best differentiated these
groups depended on the EEG measure used, the temporal
portion of the seizure, and whether ELPL, Dose, or
therapeutic response was being compared.},
Language = {eng},
Key = {fds281990}
}
@article{fds311671,
Author = {Coffey, CE and Weiner, RD and Krystal, AD},
Title = {The anticonvulsant properties of ECT.},
Journal = {Convulsive Therapy},
Volume = {12},
Number = {1},
Pages = {64-64},
Publisher = {LIPPINCOTT-RAVEN PUBL},
Year = {1996},
Month = {March},
ISSN = {0749-8055},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1996UP32900014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311671}
}
@article{fds135963,
Title = {Krystal, A.D., Weiner, R.D., Coffey, C.E., McCall, W.V. The
effect of ECT treatment number on the ictal EEG. Psychiatry
Research 62:179-189, 1996.},
Year = {1996},
Key = {fds135963}
}
@article{fds135964,
Title = {Krystal, A.D., Zaidman, C., Greenside, H.S., Weiner, R.D.,
Coffey, C.E. The largest Lyapunov exponent of the EEG during
ECT seizures as a measure of therapeutic
adequacy.},
Year = {1996},
Key = {fds135964}
}
@article{fds135989,
Title = {Krystal, A.D., Weiner, R.D., Gassert, D., McCall, W.V.,
Coffey, C.E., Sibert, T., Holsinger, T. The relative ability
of 3 ictal EEG frequency bands to differentiate ECT seizures
on the basis of electrode placement, stimulus intensity, and
therapeutic response. Convulsive Therapy 12:13-24,
1996..},
Year = {1996},
Key = {fds135989}
}
@article{fds135990,
Title = {Krystal, A.D., Greenside, H.S., Weiner, R.D., Gassert, D. A
comparison of EEG signal dynamics in waking, after
anesthesia induction and during ECT seizures.
Electroencephalography and Clinical Neurophysiology
99:129-140, 1996.},
Year = {1996},
Key = {fds135990}
}
@article{fds135991,
Title = {Krystal, A.D., Greenside, H.S. Low Dimensional Chaos in
Bipolar Disorders? (Letter to the Editor) Arch. Gen.
Psychiatry (in press).},
Year = {1996},
Key = {fds135991}
}
@article{fds135992,
Title = {Krystal, A.D., Coffey, C.E., Weiner, R.D., Holsinger, T.
Changes in seizure threshold over the ECTcourse affect
therapeutic response and are detected by ictal EEG
ratings.},
Year = {1996},
Key = {fds135992}
}
@article{fds282011,
Author = {Steffens, DC and Krystal, AD and Sibert, TE and Moore, SD and Weiner,
RD},
Title = {Cost effectiveness of maintenance ECT.},
Journal = {Convulsive Therapy},
Volume = {11},
Number = {4},
Pages = {283-284},
Year = {1995},
Month = {December},
ISSN = {0749-8055},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8919583},
Keywords = {Cost-Benefit Analysis • Electroconvulsive Therapy
• Humans • Psychotic Disorders •
economics*},
Key = {fds282011}
}
@article{fds281995,
Author = {Krystal, AD and Weiner, RD},
Title = {ECT seizure duration: reliability of manual and
computer-automated determinations.},
Journal = {Convulsive Therapy},
Volume = {11},
Number = {3},
Pages = {158-169},
Year = {1995},
Month = {September},
ISSN = {0749-8055},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8528657},
Keywords = {Adult • Aged • Cerebral Cortex •
Electroconvulsive Therapy • Electroencephalography
• Electromyography • Evoked Potentials •
Female • Humans • Male • Middle Aged •
Monitoring, Physiologic • Observer Variation •
Reproducibility of Results • Signal Processing,
Computer-Assisted* • instrumentation •
instrumentation* • physiology •
physiopathology},
Abstract = {Reliable monitoring of electroencephalographic (EEG) and
electromyographic electroconvulsive therapy (ECT) seizure
duration has become important as these assessments have
become a routine part of the clinical practice of ECT. In
this regard, accurate automated seizure duration
determinations would be particularly valuable. As a result,
the present study was performed to assess the reliability of
available computer-automated determinations of seizure
duration (Thymatron Model DGx ECT machine; Somatics, Inc.)
and to explore the factors upon which such reliability as
well as the determinations of experienced raters depend. We
found that the experienced human raters had very high
interrater reliability, significantly higher than either did
with the automated Thymatron DGx ratings. In general, the
reliability of all ratings declined in the context of
artifact, poor postictal suppression, or an EEG seizure end
point that was reached gradually. Reliability was also
greater for continuation ECT as compared with the index
course. The reliability of Thymatron DGx versus experienced
human ratings was particularly sensitive to these factors,
ranging from 0.68 when several of these factors were
simultaneously present to 0.999 when all these factors were
absent.},
Language = {eng},
Key = {fds281995}
}
@article{fds282003,
Author = {Coffey, CE and Lucke, J and Weiner, RD and Krystal, AD and Aque,
M},
Title = {Seizure threshold in electroconvulsive therapy (ECT) II. The
anticonvulsant effect of ECT.},
Journal = {Biological Psychiatry},
Volume = {37},
Number = {11},
Pages = {777-788},
Year = {1995},
Month = {June},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/7647162},
Keywords = {Adult • Aged • Bipolar Disorder • Depressive
Disorder • Dominance, Cerebral •
Electrocardiography* • Electroconvulsive Therapy •
Evoked Potentials • Female • Humans • Male
• Middle Aged • Personality Inventory •
Seizures • Sensory Thresholds • Treatment Outcome
• methods* • physiology • physiopathology
• physiopathology* • psychology •
therapy*},
Abstract = {To measure the anticonvulsant effects of a course of
electroconvulsive therapy (ECT), we used a flexible stimulus
dosage titration procedure to estimate seizure threshold at
the first and sixth ECT treatments in 62 patients with
depression who were undergoing a course of brief pulse,
constant current ECT given at moderately suprathreshold
stimulus intensity. Seizure threshold increased by
approximately 47% on average, but only 35 (56%) of the 62
patients showed a rise in seizure threshold. The rise in
seizure threshold was associated with increasing age, but
not with gender, stimulus electrode placement, or initial
seizure threshold. Dynamic impedance decreased by
approximately 5% from the first to the sixth ECT treatment,
but there was no correlation between the change in dynamic
impedance and the rise in seizure threshold. No relation was
found between the rise in seizure threshold and either
therapeutic response status or speed of response to the ECT
treatment course. These findings confirm the anticonvulsant
effect of ECT but suggest that such effects are not tightly
coupled to the therapeutic efficacy of moderately
suprathreshold ECT.},
Language = {eng},
Doi = {10.1016/0006-3223(95)00053-J},
Key = {fds282003}
}
@article{fds282007,
Author = {Coffey, CE and Lucke, J and Weiner, RD and Krystal, AD and Aque,
M},
Title = {Seizure threshold in electroconvulsive therapy: I. Initial
seizure threshold.},
Journal = {Biological Psychiatry},
Volume = {37},
Number = {10},
Pages = {713-720},
Year = {1995},
Month = {May},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/7640326},
Keywords = {Adult • Age Factors • Aged • Antipsychotic
Agents • Bipolar Disorder • Cerebral Cortex •
Depressive Disorder • Dominance, Cerebral •
Electroconvulsive Therapy • Electroencephalography*
• Evoked Potentials • Female • Humans •
Male • Middle Aged • Premedication •
Psychiatric Status Rating Scales • Retrospective
Studies • Sensory Thresholds • administration &
dosage • adverse effects • drug effects •
methods* • physiology • physiopathology •
psychology • therapy*},
Abstract = {We measured initial seizure threshold by means of a
structured stimulus dosage titration procedure in a clinical
sample of 111 depressed patients undergoing brief-pulse,
constant-current electroconvulsive therapy (ECT). Initial
seizure threshold was approximately 60 millicoumbs (mc) (10
Joules) on average, but varied widely (6-fold) across
patients. Initial seizure threshold was predicted by four
variables: electrode placement (higher with bilateral),
gender (higher in men), age (higher with increasing age),
and dynamic impedance (inverse relationship). Use of
neuroleptic medication was associated with a lower seizure
threshold. EEG seizure duration was inversely related to
initial seizure threshold, but no other relations with
seizure duration were found. These findings may have
important clinical implications for stimulus dosing
strategies in ECT.},
Language = {eng},
Doi = {10.1016/0006-3223(95)00262-F},
Key = {fds282007}
}
@article{fds281993,
Author = {Edinger, JD and Erwin, CW and Fins, AI and Marsh, GR and Krystal,
AD},
Title = {Ambulatory cassette polysomnography: findings from a large
cohort of drug-free insomnia patients.},
Journal = {Journal of Clinical Neurophysiology : Official Publication
of the American Electroencephalographic Society},
Volume = {12},
Number = {3},
Pages = {302-309},
Year = {1995},
Month = {May},
ISSN = {0736-0258},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11221789},
Keywords = {Adult • Aged • Ambulatory Care • Female
• Humans • Male • Middle Aged •
Monitoring, Physiologic • Polysomnography •
Reaction Time • Sleep Initiation and Maintenance
Disorders • Sleep Stages • Sleep, REM •
diagnosis • instrumentation* • physiology •
physiopathology*},
Abstract = {Technology for conducting ambulatory polysomnography (APSG)
has been available for more than a decade, but relatively
few studies have used this technology to study the sleep of
subjects in their usual home sleeping environments. Herein
we suggest the usefulness of this technology for the study
of normal sleepers and insomniacs, and we report our APSG
findings with a large cohort (n = 117) of drug-free insomnia
outpatients. All patients completed a sleep-history
questionnaire, a clinical interview with a sleep-disorders
clinician, and one night of APSG in their homes. Most sleep
parameters derived were consistent with previously reported
laboratory PSG findings for insomniacs, except that values
of rapid-eye-movement sleep latencies were generally shorter
than typically found in laboratory studies. Moreover,
results showed that APSG served to differentiate major age
groups and diagnostic subtypes within our larger sample, and
patient tolerance for APSG was within acceptable limits. We
conclude that APSG is a useful technique for evaluating
insomnia complaints.},
Language = {eng},
Key = {fds281993}
}
@article{fds135961,
Title = {Krystal, A.D., Greenside, H.S., Weiner, R.D., Gassert, D. A
comparison of EEG signal dynamics in waking, after
anesthesia induction and during ECT seizures.},
Year = {1995},
Key = {fds135961}
}
@article{fds135962,
Title = {Review of John S. Barlow, The Electroencephalogram: It's
Patterns and Origins, MIT Press, Cambridge, 1993, Biomedical
Instrumentation & Technology 29:363, 1995.},
Year = {1995},
Key = {fds135962}
}
@article{fds135987,
Title = {Krystal, A.D., Weiner, R.D., Coffey, C.E. The ictal EEG as a
marker of adequate stimulus intensity with unilateral ECT.
J. Neuropsychiatr. and Clin. Neurosciences 7:295-303,
1995.},
Year = {1995},
Key = {fds135987}
}
@article{fds135988,
Title = {Krystal, A.D., Weiner, R.D., Gassert, D., McCall, W.V.,
Coffey, C.E., Sibert, T., Holsinger, T. The relative ability
of 3 ictal EEG frequency bands to differentiate ECT seizures
on the basis of electrode placement, stimulus intensity, and
therapeutic response. Convulsive Therapy (In
Press).},
Year = {1995},
Key = {fds135988}
}
@article{fds281979,
Author = {Krystal, AD and Weiner, RD and Coffey, CE},
Title = {The ictal EEG as a marker of adequate stimulus intensity
with unilateral ECT.},
Journal = {The Journal of Neuropsychiatry and Clinical
Neurosciences},
Volume = {7},
Number = {3},
Pages = {295-303},
Year = {1995},
ISSN = {0895-0172},
url = {http://www.ncbi.nlm.nih.gov/pubmed/7580187},
Keywords = {Adult • Aged • Biological Markers •
Diagnosis, Computer-Assisted • Double-Blind Method
• Electroconvulsive Therapy* •
Electroencephalography* • Female • Functional
Laterality • Humans • Male • Mental Disorders
• Middle Aged • Multivariate Analysis •
Psychiatric Status Rating Scales • Regression Analysis
• Treatment Outcome • physiology • psychology
• therapy*},
Abstract = {Relative stimulus intensity above seizure threshold has been
shown to affect therapeutic outcome with unilateral ECT. The
authors sought to explore whether a multivariate ictal EEG
model would permit ongoing clinical assessment of this
parameter. Twenty-five depressed subjects were randomized to
either barely (T) or moderately (2.5T) suprathreshold ECT
treatments. Seizures in 2.5T subjects had significantly
greater ictal spectral amplitude and coherence, greater
postictal suppression, and shorter latency until ictal
slow-wave onset. A multivariate logistic regression ictal
EEG model distinguished between stimulus intensity groups
with 90% accuracy. Preliminary evidence suggests a
relationship between several ictal EEG indices and
therapeutic outcome. A multivariate ictal EEG algorithm
holds promise as a tool for clinical determination of
adequate stimulus intensity with unilateral
ECT.},
Language = {eng},
Doi = {10.1176/jnp.7.3.295},
Key = {fds281979}
}
@article{fds282004,
Author = {Krystal, AD and Weiner, RD},
Title = {ECT seizure therapeutic adequacy.},
Journal = {Convulsive Therapy},
Volume = {10},
Number = {2},
Pages = {153-164},
Year = {1994},
Month = {June},
ISSN = {0749-8055},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8069641},
Keywords = {Biological Markers • Electroconvulsive Therapy* •
Electroencephalography • Humans • adverse
effects},
Abstract = {From the beginnings of convulsive therapy, the need for some
way to assess the therapeutic adequacy of individual
treatments has been apparent. Recent work suggests that
seizure therapeutic adequacy and adverse effects are
dependent on the extent to which the stimulus exceeds the
seizure threshold (relative stimulus intensity). Applying
this information in clinical practice is problematic because
of the variable rise in the seizure threshold that takes
place over the treatment course. Attributes of the ictal
electroencephalogram (EEG) show promise for alleviating this
problem by serving as a marker of relative stimulus
intensity. Obstacles that need to be overcome in order to
implement ictal EEG indices as a relative stimulus intensity
marker in clinical practice are discussed and include
artifacts, how to determine a threshold for deciding
adequacy, variation in technique between sites, and
inter-individual EEG variation; some strategies for
overcoming these hurdles are described. It is anticipated
that an ictal EEG algorithm that addresses these issues is
likely to be of substantial clinical benefit in the practice
of electroconvulsive therapy.},
Language = {eng},
Key = {fds282004}
}
@article{fds282008,
Author = {Weiner, RD and Krystal, AD},
Title = {The present use of electroconvulsive therapy.},
Journal = {Annual Review of Medicine},
Volume = {45},
Pages = {273-281},
Year = {1994},
Month = {January},
ISSN = {0066-4219},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8198383},
Keywords = {Electroconvulsive Therapy* • Electroencephalography
• Humans • Mental Disorders • Seizures •
adverse effects • methods • physiopathology •
therapy*},
Abstract = {Physicians attempting to treat certain severe mental
disorders have recently shown renewed interest in
electroconvulsive therapy (ECT). A number of technical
innovations have made ECT safer, as well as more effective.
These innovations include oxygenation, muscular relaxation,
unilateral nondominant electrode placement, use of
brief-pulse stimuli, titrated stimulus dosing,
electroencephalographic (EEG) monitoring, determination of
seizure adequacy, and pharmacologic enhancement of treatment
response.},
Language = {eng},
Doi = {10.1146/annurev.med.45.1.273},
Key = {fds282008}
}
@article{fds135958,
Title = {Krystal AD, Weiner RD: ECT seizure therapeutic adequacy.
Convulsive Therapy 10: 153-164, 1994.},
Year = {1994},
Key = {fds135958}
}
@article{fds135959,
Title = {Krystal H, Krystal AD: Psychoanalysis and neuroscience in
relationship to dreams and creativity. In (eds., Shaw MP,
Runco MA), Creativity and Affect. New Jersey: Ablex
Publishing Corp., 1994.},
Year = {1994},
Key = {fds135959}
}
@article{fds135960,
Title = {Krystal AD, Weiner RD: Low frequency ictal EEG activity and
ECT therapeutic impact. Convulsive Therapy 9: 220-224,
1993.},
Year = {1994},
Key = {fds135960}
}
@article{fds135983,
Title = {McCall WV, Edinger JD, Krystal AD, Marsh GR: Ambulatory
polysomnogrophic differences in healthy and insomniac older
men. Ambulatory monitoring 6: 135-140, 1993.},
Year = {1994},
Key = {fds135983}
}
@article{fds135984,
Title = {Krystal AD, Weiner RD, McCall WV, Shelp F, Arias R, Smith P:
The effects of ECT stimulus dose and electrode placement on
the ictal electroencehpalogram: An intraindividual crossover
study. Biological Psychiatry 34: 759-767,
1993.},
Year = {1994},
Key = {fds135984}
}
@article{fds135985,
Title = {Weiner RD, Krystal AD: EEG monitoring of ECT seizures. In
(ed Coffey CE), The Clinical Science of Electroconvulsive
Therapy. Washington DC: American Psychiatric Press, Inc., pp
93-109, 1993.},
Year = {1994},
Key = {fds135985}
}
@article{fds135986,
Title = {Coffey CE, Lucke J, Weiner RD, Krystal AD, Aque M: Seizure
threshold in electroconvulsive therapy. I. Initial seizure
threshold. Biological Psychiatry, in press.},
Year = {1994},
Key = {fds135986}
}
@article{fds281983,
Author = {Krystal, AD and Weiner, RD and McCall, WV and Shelp, FE and Arias, R and Smith, P},
Title = {The effects of ECT stimulus dose and electrode placement on
the ictal electroencephalogram: an intraindividual crossover
study.},
Journal = {Biological Psychiatry},
Volume = {34},
Number = {11},
Pages = {759-767},
Year = {1993},
Month = {December},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8292679},
Keywords = {Adult • Aged • Analysis of Variance • Brain
• Depressive Disorder • Electroconvulsive Therapy*
• Electrodes • Electroencephalography* •
Female • Humans • Male • Middle Aged •
instrumentation • physiopathology* •
therapy*},
Abstract = {Recent evidence suggests that electroconvulsive therapy
(ECT) efficacy depends upon both electrode placement and the
degree to which stimulus dosage exceeds seizure threshold
(T), and not simply on surpassing a minimum seizure duration
as has been assumed. In light of these findings and studies
reporting ictal electroencephalogram (EEG) differences
between bilateral and unilateral ECT, we performed this
19-subject intraindividual crossover study of the effects of
dose and electrode placement on the ictal EEG. We found
ictal EEG evidence of greater seizure intensity with
bilateral than unilateral ECT and with higher dosage (2.25
T) compared with barely suprathreshold stimuli. Seizure
duration was not longer with bilateral than unilateral ECT
and actually decreased with increased dose. A number of
ictal EEG variables separated the unilateral 2.25 T and
unilateral T conditions, which reportedly differ in
efficacy, and therefore, these EEG measures show promise as
markers of treatment adequacy.},
Language = {eng},
Doi = {10.1016/0006-3223(93)90064-k},
Key = {fds281983}
}
@article{fds282001,
Author = {Krystal, AD and Weiner, RD},
Title = {Low-Frequency Ictal EEG Activity and ECT Therapeutic
Impact.},
Journal = {Convulsive Therapy},
Volume = {9},
Number = {3},
Pages = {220-224},
Year = {1993},
Month = {January},
ISSN = {0749-8055},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11941217},
Key = {fds282001}
}
@article{fds281985,
Author = {Krystal, AD and Weiner, RD and Coffey, CE and Smith, P and Arias, R and Moffett, E},
Title = {EEG evidence of more "intense" seizure activity with
bilateral ECT.},
Journal = {Biological Psychiatry},
Volume = {31},
Number = {6},
Pages = {617-621},
Year = {1992},
Month = {March},
ISSN = {0006-3223},
url = {http://www.ncbi.nlm.nih.gov/pubmed/1581442},
Keywords = {Cerebral Cortex • Depressive Disorder • Dominance,
Cerebral • Electroconvulsive Therapy •
Electroencephalography* • Evoked Potentials •
Humans • Middle Aged • Signal Processing,
Computer-Assisted • instrumentation • methods*
• physiology • physiology* • physiopathology
• psychology • therapy*},
Language = {eng},
Doi = {10.1016/0006-3223(92)90249-y},
Key = {fds281985}
}
@article{fds281997,
Author = {McCall, WV and Erwin, CW and Edinger, JD and Krystal, AD and Marsh,
GR},
Title = {Ambulatory polysomnography: technical aspects and normative
values.},
Journal = {Journal of Clinical Neurophysiology : Official Publication
of the American Electroencephalographic Society},
Volume = {9},
Number = {1},
Pages = {68-77},
Year = {1992},
Month = {January},
ISSN = {0736-0258},
url = {http://www.ncbi.nlm.nih.gov/pubmed/1552010},
Keywords = {Ambulatory Care • Cerebral Cortex • Circadian
Rhythm • Electroencephalography • Humans •
Monitoring, Physiologic • Signal Processing,
Computer-Assisted • Sleep Disorders • Sleep Stages
• Sleep, REM • diagnosis* • instrumentation*
• physiology • physiology* •
physiopathology},
Abstract = {Ambulatory polysomnographic (APSG) assessment of sleep
disorders is now possible, but the technique of APSG is
sufficiently different from in-laboratory PSG that normative
data from in-laboratory PSG may not apply to APSG. This
paper reviews the technical aspects of APSG and presents
normative APSG data from 20 older healthy males. Subjects
underwent medical and psychiatric screening before
completing APSG in their homes. Total sleep time and the
rapid-eye-movement sleep latency (RL) were both shorter than
those reported by others using traditional in-laboratory
techniques. The shorter total sleep may be related to
behaviors at home that impinge upon sleep. The shorter RL
may be related to differences in calculation methods.
Periodic limb movements were common in our subjects but did
not contribute to sleep disturbance. We conclude that APSG
is sufficiently different from traditional PSG as to warrant
collection of a large normative data base.},
Language = {eng},
Key = {fds281997}
}
@article{fds281988,
Author = {Weiner, RD and Krystal, AD and Coffey, CE and Smith,
P},
Title = {The electrophysiology of ECT: relevance to mechanism of
action.},
Journal = {Clinical Neuropharmacology},
Volume = {15 Suppl 1 Pt A},
Pages = {671A-672A},
Year = {1992},
ISSN = {0362-5664},
url = {http://www.ncbi.nlm.nih.gov/pubmed/1498995},
Keywords = {Animals • Electroconvulsive Therapy* •
Electrophysiology • Humans},
Language = {eng},
Doi = {10.1097/00002826-199201001-00347},
Key = {fds281988}
}
@article{fds282002,
Author = {Weiner, RD and Coffey, CE and Krystal, AD},
Title = {The monitoring and management of electrically induced
seizures.},
Journal = {The Psychiatric Clinics of North America},
Volume = {14},
Number = {4},
Pages = {845-869},
Year = {1991},
Month = {December},
ISSN = {0193-953X},
url = {http://www.ncbi.nlm.nih.gov/pubmed/1771151},
Keywords = {Electroconvulsive Therapy • Electroencephalography
• Humans • Monitoring, Physiologic • Seizures
• Time Factors • etiology • methods* •
physiopathology* • therapy},
Abstract = {Because induced seizures have such a fundamental influence
on both beneficial and adverse effects associated with ECT,
it is crucial that they be monitored as effectively as
possible. In practice this process involves a combination of
both motor and EEG monitoring. The technology for such
monitoring, although not overly sophisticated, is also not
trivial, and a certain amount of training is required before
a practitioner can meaningfully interpret this type of
information. Efforts to standardize monitoring practices, at
least within a particular ECT program, are also indicated.
Our knowledge of what constitutes an adequate seizure is
limited, with duration still the primary focus. Future
studies of ictal electrophysiology may well provide better
answers in this regard. One area where already accomplished
work has proved productive involves the delineation of many
of the factors which influence seizure threshold and
duration. On the basis of these data, practitioners now can
exert considerably greater control over such measures, and
thereby make more optimal use of this treatment
modality.},
Language = {eng},
Doi = {10.1016/s0193-953x(18)30272-7},
Key = {fds282002}
}
@article{fds282010,
Author = {Krystal, AD and McEvoy, JP},
Title = {Shared features of neuroleptic malignant syndrome and
alcohol abuse complications.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {51},
Number = {12},
Pages = {523},
Year = {1990},
Month = {December},
ISSN = {0160-6689},
url = {http://www.ncbi.nlm.nih.gov/pubmed/2258367},
Keywords = {Adult • Diagnosis, Differential • Ethanol •
Fluphenazine • Humans • Male • Neuroleptic
Malignant Syndrome • Rhabdomyolysis • Substance
Withdrawal Syndrome • adverse effects • adverse
effects* • analogs & derivatives • diagnosis
• diagnosis* • etiology •
psychology},
Language = {eng},
Key = {fds282010}
}
@article{fds281978,
Author = {Krystal, A and Krishnan, KR and Raitiere, M and Poland, R and Ritchie,
JC and Dunnick, NR and Hanada, K and Nemeroff, CB},
Title = {Differential diagnosis and pathophysiology of Cushing's
syndrome and primary affective disorder.},
Journal = {The Journal of Neuropsychiatry and Clinical
Neurosciences},
Volume = {2},
Number = {1},
Pages = {34-43},
Year = {1990},
ISSN = {0895-0172},
url = {http://www.ncbi.nlm.nih.gov/pubmed/1967010},
Keywords = {Adrenocorticotropic Hormone • Aged • Anxiety
Disorders • Bipolar Disorder •
Corticotropin-Releasing Hormone • Cushing Syndrome
• Delirium, Dementia, Amnestic, Cognitive Disorders
• Depressive Disorder • Diagnosis, Differential
• Female • Humans • Hydrocortisone •
Middle Aged • Psychotropic Drugs • Tomography,
X-Ray Computed • blood • diagnosis •
diagnosis* • drug therapy • physiology •
physiopathology • therapeutic use},
Abstract = {Most patients with major depression have increased 24-hour
urinary free cortisol and cortisol nonsuppression after
dexamethasone administration, which are cornerstones of a
diagnosis of Cushing's syndrome. Similarly, Cushing's
syndrome patients often suffer from major psychiatric
syndromes, most often depression. These similarities between
the two conditions sometimes make it difficult to
differentiate them and have led some investigators to
suggest they are two points on a spectrum of endocrinologic
dysfunction. This article reviews the literature comparing
Cushing's syndrome and primary affective disorder and
presents two cases that illustrate just how closely these
diseases may resemble one another.},
Language = {eng},
Doi = {10.1176/jnp.2.1.34},
Key = {fds281978}
}
%% Papers Published
@article{fds363090,
Author = {Scangos, K and Makhoul, G and Khambhati, AN and Sellers, KK and Chang,
EF and Krystal, AD},
Title = {Corticocortical Evoked Potentials and Patient Response
Reveal Networks Underlying Depression},
Journal = {Biological Psychiatry},
Volume = {87},
Number = {9},
Pages = {S157-S157},
Year = {2020},
Key = {fds363090}
}
@article{fds363091,
Author = {Lunsford-Avery, JR and Krystal, AD and Carskadon, MA and Kollins,
SH},
Title = {SLEEP ASSOCIATED WITH EXECUTIVE FUNCTIONING AMONG
ADOLESCENTS ACROSS THE ADHD CONTINUUM},
Journal = {Sleep},
Volume = {43},
Pages = {A373-A373},
Year = {2020},
Key = {fds363091}
}
@article{fds363092,
Author = {McCall, WV and Benca, RM and Rumble, M and Krystal,
AD},
Title = {DO THE SUBJECTIVE EFFECTS OF HYPNOTIC MEDICATIONS RESULT IN
UNBLINDING OF TREATMENT ASSIGNMENT IN HYPNOTIC RANDOMIZED
CLINICAL TRIALS?},
Journal = {Sleep},
Volume = {43},
Pages = {A181-A181},
Year = {2020},
Key = {fds363092}
}
@article{fds363093,
Author = {Ohayon, MM and Krystal, AD and Black, J and Shapiro, CM and Sullivan, S and Swick, TJ and Wells, CC},
Title = {FACTORS ASSOCIATED WITH THE CONTINUOUS USE OF PSYCHOTROPIC
TREATMENTS FOR NARCOLEPSY},
Journal = {Sleep},
Volume = {43},
Pages = {A294-A294},
Year = {2020},
Key = {fds363093}
}
@article{fds363095,
Author = {Ohayon, MM and Sullivan, SS and Krystal, AD and Black, J and Swick, TJ and Shapiro, CM and Wells, CC},
Title = {Narcolepsy Symptoms are Highly Persistent over Time Despite
Treatment},
Journal = {Annals of Neurology},
Volume = {86},
Pages = {S122-S122},
Publisher = {WILEY},
Year = {2019},
Month = {October},
Key = {fds363095}
}
@article{fds363096,
Author = {Ohayon, MM and Sullivan, SS and Black, J and Krystal, AD and Shapiro,
CM and Swick, TJ and Wells, CC},
Title = {Longitudinal Assessment of Psychotropic Treatments for
Narcolepsy},
Journal = {Annals of Neurology},
Volume = {86},
Pages = {S212-S212},
Publisher = {WILEY},
Year = {2019},
Month = {October},
Key = {fds363096}
}
@article{fds346508,
Author = {Doghramji, K and Davis, CW and Patroneva, A and Schwartz, J-C and Scart-Gres, C and Robert, P and Wanaski, SP and Krystal,
AD},
Title = {PITOLISANT IN COMBINATION WITH OTHER MEDICATIONS FOR THE
MANAGEMENT OF NARCOLEPSY},
Journal = {Sleep},
Volume = {42},
Pages = {1 pages},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2019},
Month = {April},
Key = {fds346508}
}
@article{fds363094,
Author = {Ohayon, MM and Krystal, AD},
Title = {SLEEP IMPACTS OF NOCTURIA IN A LONGITUDINAL
STUDY},
Journal = {Sleep Medicine},
Volume = {64},
Pages = {S284-S285},
Year = {2019},
Key = {fds363094}
}
@article{fds346509,
Author = {Ohayon, MM and Black, J and Krystal, AD and Shapiro, CM and Swick, T and Rogan, R and Well, CC},
Title = {Longitudinal Evolution of Narcolepsy Symptoms in Simplex and
Multiplex Families},
Journal = {Annals of Neurology},
Volume = {84},
Pages = {S129-S130},
Publisher = {WILEY},
Year = {2018},
Month = {October},
Key = {fds346509}
}
@article{fds346510,
Author = {Beaulieu-Bonneau, S and Edinger, JD and Ivers, H and Krystal, AD and Morin, CM},
Title = {Weekly changes in sleep and insomnia symptoms during acute
treatment of persistent insomnia with behavioural or
pharmacological therapy},
Journal = {Journal of Sleep Research},
Volume = {27},
Pages = {2 pages},
Publisher = {WILEY},
Year = {2018},
Month = {September},
Key = {fds346510}
}
@article{fds346511,
Author = {Lunsford-Avery, JR and Kollins, SH and Krystal,
AD},
Title = {0762 Sleeping at Home: Feasibility and Tolerability of
Ambulatory Polysomnography for Use with Adolescents with
Attention-Deficit/Hyperactivity Disorder},
Journal = {Sleep},
Volume = {41},
Number = {suppl_1},
Pages = {A283-A284},
Publisher = {Oxford University Press (OUP)},
Year = {2018},
Month = {April},
url = {http://dx.doi.org/10.1093/sleep/zsy061.761},
Doi = {10.1093/sleep/zsy061.761},
Key = {fds346511}
}
@article{fds346513,
Author = {Rumble, ME and Dickson, D and McCall, WV and Krystal, AD and Newman, JC and Notermann, S and Rosenquist, PB and Benca, RM},
Title = {0639 A Preliminary Report from the “REST-IT” Study:
Self-reported Eveningness and Actigraphic Delayed Sleep
Timing Correlate with Suicidal Ideation in Individuals with
Depression and Insomnia},
Journal = {Sleep},
Volume = {41},
Number = {suppl_1},
Pages = {A237-A238},
Publisher = {Oxford University Press (OUP)},
Year = {2018},
Month = {April},
url = {http://dx.doi.org/10.1093/sleep/zsy061.638},
Doi = {10.1093/sleep/zsy061.638},
Key = {fds346513}
}
@article{fds346512,
Author = {Blanco, MB and Klopfer, PH and Krystal, AD},
Title = {To arouse or not to arouse: physiological responses from
active thermogenesis versus thermoconforming in hibernating
dwarf lemurs},
Journal = {American Journal of Physical Anthropology},
Volume = {165},
Pages = {30-30},
Publisher = {WILEY},
Year = {2018},
Month = {April},
Key = {fds346512}
}
@article{fds346514,
Author = {Morin, CM and Edinger, JD and Krystal, AD and Beaulieu-Bonneau, S and Ivers, H and Guay, B and Cartwright, A and Solano, A and Busby,
M},
Title = {0341 SEQUENTIAL THERAPIES FOR COMORBID AND PRIMARY INSOMNIA:
A RANDOMIZED CONTROLLED TRIAL},
Journal = {Sleep},
Volume = {40},
Number = {suppl_1},
Pages = {A127-A127},
Publisher = {Oxford University Press (OUP)},
Year = {2017},
Month = {April},
url = {http://dx.doi.org/10.1093/sleepj/zsx050.340},
Doi = {10.1093/sleepj/zsx050.340},
Key = {fds346514}
}
@article{fds346515,
Author = {Edinger, JD and Manber, R and Krystal, AD and Buysse,
DJ},
Title = {0335 DOES OBJECTIVE SLEEP DURATION MODERATE TREATMENT
RESPONSE IN PATIENT WITH COMORBID DEPRESSION AND INSOMNIA?
A REPORT FROM THE TRIAD STUDY},
Journal = {Sleep},
Volume = {40},
Number = {suppl_1},
Pages = {A124-A124},
Publisher = {Oxford University Press (OUP)},
Year = {2017},
Month = {April},
url = {http://dx.doi.org/10.1093/sleepj/zsx050.334},
Doi = {10.1093/sleepj/zsx050.334},
Key = {fds346515}
}
@article{fds346516,
Author = {Sateia, MJ and Buysse, D and Krystal, AD and Neubauer, DN and Heald,
JL},
Title = {0395 CLINICAL PRACTICE GUIDELINE FOR THE PHARMACOLOGIC
TREATMENT OF CHRONIC INSOMNIA IN ADULTS: AN AMERICAN ACADEMY
OF SLEEP MEDICINE CLINICAL PRACTICE GUIDELINE},
Journal = {Sleep},
Volume = {40},
Number = {suppl_1},
Pages = {A147-A147},
Publisher = {Oxford University Press (OUP)},
Year = {2017},
Month = {April},
url = {http://dx.doi.org/10.1093/sleepj/zsx050.394},
Doi = {10.1093/sleepj/zsx050.394},
Key = {fds346516}
}
@article{fds329830,
Author = {Dieffenderfer, J and Krystal, A and Bozkurt, A},
Title = {Shedding light to sleep studies},
Journal = {Smart Structures and Materials 2005: Active Materials:
Behavior and Mechanics},
Volume = {10352},
Publisher = {SPIE},
Year = {2017},
Month = {January},
ISBN = {9781510611610},
url = {http://dx.doi.org/10.1117/12.2275625},
Abstract = {This paper presents our efforts in the development of a
small wireless, flexible bandage sized near-infrared
spectroscopy (NIRS) system for sleep analysis. The current
size of the system is 2.8 cm × 1.7 cm × 0.6 cm. It is
capable of performing NIRS with 660nm, 940nm and 850nm
wavelengths for up to 11 hours continuously. The device is
placed on the forehead to measure from the prefrontal cortex
and the raw data is continuously streamed over Bluetooth to
a nearby data aggregator such as a smartphone for post
processing and cloud connection. In this study, we performed
traditional polysomnography simultaneously with NIRS to
evaluate agreement with traditional measures of sleep and to
provide labelled data for future work involving learning
algorithms. Ultimately, we expect a machine learning
algorithm to be able to generate characterization of sleep
states comparable to traditional methods based on this
biophotonics data. The system also includes an inertial
measurement unit and the features that can be extracted from
the presented system include sleep posture, heart rate,
respiratory rate, relative change in oxy and deoxy
hemoglobin concentrations and tissue oxygenation and
cerebral arterial oxygen extracted from these. Preliminary
proof of concept results are promising and demonstrate the
capability to measure heart rate, respiratory rate and
slow-wave-sleep stages. This system serves as a prototype to
evaluate the potential of a small bandage-size
continuous-wave NIRS device to be a useful means of studying
sleep.},
Doi = {10.1117/12.2275625},
Key = {fds329830}
}
@article{fds322850,
Author = {Manber, R and Buysse, DJ and Edinger, J and Krystal, A and Luther, JF and Wisniewski, SR and Trockel, M and Kraemer, HC and Thase,
ME},
Title = {Efficacy of Cognitive-Behavioral Therapy for Insomnia
Combined With Antidepressant Pharmacotherapy in Patients
With Comorbid Depression and Insomnia: A Randomized
Controlled Trial.},
Journal = {The Journal of Clinical Psychiatry},
Volume = {77},
Number = {10},
Pages = {e1316-e1323},
Year = {2016},
Month = {October},
url = {http://dx.doi.org/10.4088/JCP.15m10244},
Abstract = {OBJECTIVES: The Treatment of Insomnia and Depression (TRIAD)
study evaluated the efficacy of combining depression
pharmacotherapy (using MED, an ecologically valid and
generalizable antidepressant medication algorithm) with
cognitive-behavioral therapy for insomnia (CBT-I) among
individuals with comorbid insomnia and major depressive
disorder (MDD) to determine if change in insomnia severity
mediates antidepressant outcome. METHODS: This 16-week,
3-site, randomized controlled trial (RCT) randomly assigned
150 participants (recruited between March 2009 and August
2013), who met DSM-IV-TR criteria for insomnia and MDD and
were not receiving treatment for either, to receive
depression pharmacotherapy plus 7 sessions of either CBT-I
or a credible control therapy for insomnia (CTRL).
Depression pharmacotherapy followed a standardized 2-step
algorithm, which included escitalopram, sertraline, and
desvenlafaxine in a prescribed sequence. Primary measures
were the Hamilton Depression Rating Scale and the depression
module of the Structured Clinical Interview for DSM-IV Axis
I Disorders, Research Version, Nonpatient Edition,
administered by raters masked to treatment assignment, and
the self-administered Insomnia Severity Index (ISI).
RESULTS: CBT-I was superior to CTRL in reducing insomnia
severity (P = .028). The overall difference in depression
remission between the treatments was not statistically
significant (44% in CBT-I and 36% in CTRL; number needed to
treat = 15). However, planned secondary analysis revealed
that improvements in insomnia at week 6 mediated eventual
remission from depression, with early change in ISI
predicting depression remission in the CBT-I (P = .0002) but
not in the CTRL arm (P = .26). CONCLUSIONS: CBT-I is an
efficacious treatment for insomnia comorbid with MDD among
patients treated with antidepressant medications.
Improvement in insomnia may be related to the change in
depression. Future studies should identify which patients
are most likely to benefit from the addition of an
insomnia-focused therapy to standard antidepressant
treatments. TRIAL REGISTRATION: ClinicalTrials.gov
identifier NCT00767624.},
Doi = {10.4088/JCP.15m10244},
Key = {fds322850}
}
@article{fds311656,
Author = {Leuchter, AF and Cook, IA and Feifel, D and Goethe, JW and Husain, M and Carpenter, LL and Thase, ME and Krystal, AD and Philip, NS and Hunter,
AM and Burke, WJ and Howland, RH and Sheline, YI and Aaronson, ST and Iosifescu, DV and O'Reardon, J and Gilmer, WS and Jain, R and Bugoyne,
K and Massaro, J and Lisanby, SH and George, MS},
Title = {Can We Use Brain Oscillations to Guide Treatment of
MDD?},
Journal = {Biological Psychiatry},
Volume = {77},
Number = {9},
Pages = {37S-38S},
Publisher = {ELSEVIER SCIENCE INC},
Year = {2015},
Month = {May},
ISSN = {0006-3223},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352207500097&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311656}
}
@article{fds281843,
Author = {Valero-Sarmiento, JM and Bhattacharya, S and Krystal, A and Bozkurt,
A},
Title = {Towards injectable biophotonic sensors for physiological
monitoring of animals},
Journal = {Proceedings of Ieee Sensors},
Volume = {2014-December},
Number = {December},
Pages = {503-506},
Publisher = {IEEE},
Year = {2014},
Month = {December},
ISBN = {9781479901616},
ISSN = {1930-0395},
url = {http://dx.doi.org/10.1109/ICSENS.2014.6985045},
Abstract = {We present a novel subcutaneous biophotonics sensor system
for continuous monitoring of hemodynamic parameters in
animals. This sensor incorporates surface-mount light
sources and photodetectors in the form factors of glass
capsules used for microchip implants containing radio
frequency identification integrated circuits. In this study,
we investigated the potential of such capsules to perform
reflectance-based pulse oximetry measurements and the
possibility of using inductive coupling to power such
systems.},
Doi = {10.1109/ICSENS.2014.6985045},
Key = {fds281843}
}
@article{fds311657,
Author = {Tek, C and Palmese, LB and Krystal, AD and DeGeorge, PC and Reutenauer,
EL and Guloksuz, S},
Title = {The Impact of Eszopiclone Insomnia Treatment on Cognition in
Schizophrenia: A Double-blind, Randomized,
Placebo-controlled Trial},
Journal = {Biological Psychiatry},
Volume = {75},
Number = {9},
Pages = {341S-342S},
Publisher = {ELSEVIER SCIENCE INC},
Year = {2014},
Month = {May},
ISSN = {0006-3223},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000334101802207&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311657}
}
@article{fds281862,
Author = {Deng, ZD and Peterchev, AV and Krystal, AD and Luber, B and McClintock,
SM and Husain, MM and Lisanby, SH},
Title = {Topography of seizures induced by electroconvulsive therapy
and magnetic seizure therapy},
Journal = {International Ieee/Embs Conference on Neural Engineering,
Ner},
Pages = {577-580},
Publisher = {IEEE},
Year = {2013},
Month = {December},
ISBN = {9781467319690},
ISSN = {1948-3546},
url = {http://dx.doi.org/10.1109/NER.2013.6696000},
Abstract = {We present the first topographical characterization of
seizures induced by ultrabrief pulse width right unilateral
electroconvulsive therapy (ECT) and magnetic seizure therapy
(MST). Topographical electroencephalogram (EEG) was acquired
during treatments in a randomized controlled trial
contrasting the efficacy and safety of ECT and MST. EEG
power topography within delta, theta, alpha, and beta
frequency bands were assessed using wavelet and current
source density analysis. ECT showed greater increases in EEG
power relative to baseline in all frequencies during the
early and mid-ictal periods, and decrease in power during
the post-ictal period. MST seizures showed little change in
ictal EEG power and post-ictal suppression relative to
baseline. Compared to MST, ECT showed greater changes in
power in all frequencies. Contrasting the seizure topography
induced by ECT and MST can provide insights into the impact
of stimulation focality on the patterns of seizure onset and
spread, factors thought to be critical to the efficacy and
side effects of convulsive therapy. © 2013
IEEE.},
Doi = {10.1109/NER.2013.6696000},
Key = {fds281862}
}
@article{fds311658,
Author = {Krystal, AD and Preud'homme, XA and Goforth, HW},
Title = {A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF
ESZOPICLONE FOR THE TREATMENT OF INSOMNIA IN PATIENTS WITH
CHRONIC LOW BACK PAIN},
Journal = {Sleep},
Volume = {35},
Pages = {A216-A216},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996501158&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311658}
}
@article{fds311659,
Author = {Buysse, DJ and Krystal, AD and Johnston, K and Dodds, N and Yu, L and Giang, R and Pilkonis, P},
Title = {SLEEP AND HEALTH-RELATED FUNCTION IN A CLINICAL SAMPLE AS
MEASURED BY PROMIS (PATIENT-REPORTED OUTCOMES MEASUREMENT
INFORMATION SYSTEM)},
Journal = {Sleep},
Volume = {35},
Pages = {A133-A133},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996500386&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311659}
}
@article{fds311660,
Author = {Krystal, AD and Roth, T and Pong, A and Stet, L and Ivgy-May,
N},
Title = {EFFICACY AND SAFETY OF ESMIRTAZAPINE IN ELDERLY PATIENTS
WITH PRIMARY INSOMNIA IN A 2-WEEK SLEEP LABORATORY
TRIAL},
Journal = {Sleep},
Volume = {35},
Pages = {A222-A222},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996501175&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311660}
}
@article{fds311661,
Author = {Roth, T and Hull, SG and Singh, NN and Steinberg, F and Krystal,
AD},
Title = {GENDER EFFECTS OF 1.75 MG AND 3.5 MG ZOLPIDEM TARTRATE
SUBLINGUAL TABLETS FORMULATED WITH A CARBONATE-BICARBONATE
BUFFER ON SLEEP ONSET FOLLOWING MIDDLE-OF-THE-NIGHT
AWAKENING AND ON NEXT-DAY RESIDUAL EFFECTS},
Journal = {Sleep},
Volume = {35},
Pages = {A225-A226},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996501186&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311661}
}
@article{fds311662,
Author = {Edinger, JD and Means, MK and Krystal, AD},
Title = {ARE INSOMNIA SUFFERERS' DAYTIME DEFICITS PRODUCTS OF
SUBJECTIVE DISTORTIONS?},
Journal = {Sleep},
Volume = {35},
Pages = {A230-A230},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996501199&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311662}
}
@article{fds311663,
Author = {Edinger, JD and Means, MK and Krystal, AD},
Title = {DOES HYPERAROUSAL INCREASE DAYTIME ERROR PRONENESS AMONG
INSOMNIA SUFFERERS?},
Journal = {Sleep},
Volume = {35},
Pages = {A214-A214},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996501151&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311663}
}
@article{fds311668,
Author = {Preud'homme, XA and Lohri, J and Amundsen, CL and Peterson, A and Webster, GD and Krystal, AD},
Title = {NOCTURIA IN SUBJECTS WITH OVERACTIVE BLADDER SYNDROME (OAB):
WHAT WAKES THEM UP?},
Journal = {Sleep},
Volume = {35},
Pages = {A309-A309},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2012},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000312996502157&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311668}
}
@article{fds346517,
Author = {Herring, WJ and Snyder, E and Paradis, E and Hutzelmann, J and Liu, M-C and Snavely, D and Walsh, J and Krystal, A and Roth, T and Michelson,
D},
Title = {Suvorexant, an orexin receptor antagonist, in preventing
symptom return in patients with insomnia after 1 year of
treatment: a randomised, double-blind, placebo-controlled
study},
Journal = {Journal of Sleep Research},
Volume = {21},
Pages = {351-351},
Year = {2012},
Key = {fds346517}
}
@article{fds363097,
Author = {Connor, K and Budd, K and Snavely, D and Liu, K and Hutzel-Mann, J and Benca, R and Krystal, A and Roth, T and Michelson, D and Herring,
WJ},
Title = {Efficacy and safety of suvorexant, an orexin receptor
antagonist, in patients with primary insomnia: a 3-month
phase 3 trial (trial #1)},
Journal = {Journal of Sleep Research},
Volume = {21},
Pages = {97-97},
Year = {2012},
Key = {fds363097}
}
@article{fds311681,
Author = {Rose, JE and McClernon, FJ and Froeliger, B and Behm, FM and Preud'homme, X and Krystal, AD},
Title = {Repetitive Transcranial Magnetic Stimulation (rTMS) of the
Superior Frontal Gyrus Modulates Craving for
Cigarettes},
Journal = {Biological Psychiatry},
Volume = {69},
Number = {9},
Pages = {277S-278S},
Publisher = {ELSEVIER SCIENCE INC},
Year = {2011},
Month = {May},
ISSN = {0006-3223},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000290641800874&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311681}
}
@article{fds311673,
Author = {Palmese, LB and DeGeorge, PC and Srihari, VH and Wexler, BE and Krystal,
AD and Tek, C},
Title = {SLEEP PATTERNS OF INDIVIDUALS WITH SCHIZOPHRENIA},
Journal = {Schizophrenia Bulletin},
Volume = {37},
Pages = {277-277},
Publisher = {OXFORD UNIV PRESS},
Year = {2011},
Month = {March},
ISSN = {0586-7614},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000287746000786&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311673}
}
@article{fds311711,
Author = {Lankford, A and Krystal, AD and Dorsey, B and Rogowski, R and Ludington,
E and Durrence, H and Davis, CS and Roth, T},
Title = {PATIENT-REPORTED SYMPTOM IMPROVEMENT IN SLEEP MAINTENANCE
ENDPOINTS IN ADULT AND ELDERLY PATIENTS WITH INSOMNIA
TREATED WITH DOXEPIN 3 AND 6 MG},
Journal = {Sleep},
Volume = {34},
Pages = {A175-A175},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2011},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299834400511&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311711}
}
@article{fds311665,
Author = {Preud'homme, XA and Amundsen, CL and Webster, GD and Jiang, W and Kuchibhatla, M and Krystal, AD},
Title = {AUTONOMIC NERVOUS SYSTEM ACTIVITY PRECEDING NOCTURIA IN
OLDER ADULTS},
Journal = {Sleep},
Volume = {34},
Pages = {A241-A241},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2011},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299834400699&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311665}
}
@article{fds311674,
Author = {Krystal, AD and Lankford, A and Dorsey, B and Rogowski, R and Ludington,
E and Durrence, H and Roth, T},
Title = {IMPROVEMENT IN SLEEP MAINTENANCE AND EARLY MORNING
AWAKENINGS IN ADULT AND ELDERLY PATIENTS WITH INSOMNIA
TREATED WITH DOXEPIN 3 AND 6 MG},
Journal = {Sleep},
Volume = {34},
Pages = {A182-A182},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2011},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299834400532&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311674}
}
@article{fds311678,
Author = {Krystal, AD and Grinnell, T and Spalding, W and Zummo, J and Schweizer,
E and Marshall, RD},
Title = {A POSTHOC ANALYSIS OF ESZOPICLONE EFFECTS ON CARDIOMETABOLIC
INDICES OF HYPERAROUSAL IN THE TREATMENT OF PRIMARY
INSOMNIA},
Journal = {Sleep},
Volume = {34},
Pages = {A175-A175},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2011},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299834400512&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311678}
}
@article{fds311686,
Author = {Manber, R and Suh, S and Buysse, DJ and Edinger, JD and Cardell, C and Cardell, J and Krystal, AD},
Title = {OBSTRUCTIVE SLEEP APNEA (OSA) IN MAJOR DEPRESSIVE
DISORDER},
Journal = {Sleep},
Volume = {34},
Pages = {A256-A257},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2011},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299834400748&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311686}
}
@article{fds363098,
Author = {Moore, P and Zammit, G and Yen, M and Lankford, D and Scharf, M and Rosenberg, R and Edinger, J and Krystal, A},
Title = {THE INFLUENCE OF MORNINGNESS-EVENINGNESS ON LATENCY TO
PERSISTENT SLEEP IN A MODEL OF TRANSIENT
INSOMNIA},
Journal = {Sleep},
Volume = {32},
Pages = {A60-A60},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2009},
Month = {January},
Key = {fds363098}
}
@article{fds363099,
Author = {Sloane, PD and Krystal, A and Harrington, JJ and Williams,
C},
Title = {MR1 abnormalities and circadian rhythm disturbances in
persons with dementia},
Journal = {Journal of the American Geriatrics Society},
Volume = {56},
Number = {4},
Pages = {S59-S59},
Publisher = {BLACKWELL PUBLISHING},
Year = {2008},
Month = {April},
Key = {fds363099}
}
@article{fds311717,
Author = {Edinger, JD and Wyatt, JK and Olsen, MK and Stechuchak, KM and Carney,
CE and Chiang, A and Krystal, AD and Means, MK and Radtke,
RA},
Title = {How valid are the DSM-IV-TR and ICSD-2 insomnia nosologies?
Preliminary results from a multi-trait/multi-method
diagnostic trial},
Journal = {Sleep},
Volume = {31},
Pages = {A249-A249},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001189&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311717}
}
@article{fds311718,
Author = {Richey, SM and Weiner, RD and Edinger, JD and Preud'homme, X and Carney,
CE and Krystal, AD},
Title = {Change in sleep correlates with change in post-dexamethasone
cortisol in patients with refractory depression treated with
ECT},
Journal = {Sleep},
Volume = {31},
Pages = {A244-A244},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001174&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311718}
}
@article{fds311675,
Author = {Krystal, AD and Scharf, MB and Mordy, C and Singh, N and Maytom,
M},
Title = {Pharmacokinetics of a low dose, sublingual formulation of
zolpidem tartrate in elderly subjects},
Journal = {Sleep},
Volume = {31},
Pages = {A234-A235},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001142&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311675}
}
@article{fds311679,
Author = {Krystal, AD and Kahn, R and Maguire, Y and Singh, N and Maytom,
M},
Title = {A pharmacokinetic study of the co-administration of a high
fat meal with a low dose, sublingual formulation of zolpidem
tartrate},
Journal = {Sleep},
Volume = {31},
Pages = {A34-A34},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419000105&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311679}
}
@article{fds311683,
Author = {Ohayon, MM and Guilleminault, C and Black, J and Wells, C and Krystal,
AD},
Title = {Evolution of narcolepsy symptoms in families},
Journal = {Sleep},
Volume = {31},
Pages = {A213-A213},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001079&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311683}
}
@article{fds311689,
Author = {Rosenberg, R and Krystal, AD and Novak, J and Maguire, Y and Mordy, C and Singh, N and Maytom, M},
Title = {Frequency and timing of middle-of-the-night (MOTN)
awakenings as described using an interactive voice response
system},
Journal = {Sleep},
Volume = {31},
Pages = {A235-A235},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001144&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311689}
}
@article{fds311693,
Author = {Roth, T and Krystal, AD and Maguire, Y and Singh, N and Maytom,
M},
Title = {Pharmacokinetics of the sublingual zolpidem tartrate 3.5mg
lozenge compared to the oral zolpidem tartrate 10 mg
tablet},
Journal = {Sleep},
Volume = {31},
Pages = {A235-A235},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001143&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311693}
}
@article{fds311721,
Author = {Carney, CE and Edinger, JD and Olsen, MK and Stechuchak, KM and Krystal,
AD and Wyatt, JK},
Title = {Inter-rater reliability for insomnia diagnoses derived from
the duke structured interview for sleep disorders},
Journal = {Sleep},
Volume = {31},
Pages = {A250-A250},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2008},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000255419001192&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311721}
}
@article{fds311676,
Author = {Krystal, AD and Dinges, DF},
Title = {Modafinil improves performance requiring sustained attention
in patients with narcolepsy},
Journal = {Annals of Neurology},
Volume = {62},
Pages = {S80-S80},
Publisher = {WILEY-LISS},
Year = {2007},
Month = {January},
ISSN = {0364-5134},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000249930600318&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311676}
}
@article{fds363100,
Author = {Janicak, PG and Nahas, Z and Lisanby, S and Solvason, HB and Sampson, S and McDonald, W and Marangell, L and Rosenquist, P and McCall, V and Kimball, J and O'Reardon, J and Loo, C and Husain, M and Krystal, A and Gilmer, W and Demitrack, M and Schatzberg, A},
Title = {Durability of acute response to TMS in the treatment of
major depression: Relapse during a continuation
pharmacotherapy extension study},
Journal = {Biological Psychiatry},
Volume = {61},
Number = {8},
Pages = {176S-176S},
Year = {2007},
Key = {fds363100}
}
@article{fds363101,
Author = {Krystal, A and Fava, M and Pollack, M and Rubens, R and Schaefer, K and Amato, D and Roth, T},
Title = {Sleep outcomes following eszopiclone discontinuation in
patients with primary insomnia co-existing with major
depressive disorder or generalized anxiety
disorder},
Journal = {Biological Psychiatry},
Volume = {61},
Number = {8},
Pages = {84S-84S},
Year = {2007},
Key = {fds363101}
}
@article{fds363103,
Author = {Aaronson, S and Avery, D and Canterbury, R and Daskalakis, ZJ and Demitrack, MA and Fitzgerald, P and George, MS and Gilmer, WS and Gutierrez, R and Husain, MM and Isenberg, K and Janicak, P and Krystal,
A and Lisanby, SH and Loo, C and Maixner, D and Marangell, L and McDonald,
W and Nahas, Z and O'Reardon, JP and Richelson, E and Rosenquist, P and Sackeim, H and Sampson, S and Solvason, HB},
Title = {Transcranial magnetic stimulation: Effectiveness and safety
in a randomized, controlled, multisite clinical trial and an
open-label extension study},
Journal = {Neuropsychopharmacology},
Volume = {31},
Pages = {S230-S230},
Publisher = {NATURE PUBLISHING GROUP},
Year = {2006},
Month = {December},
Key = {fds363103}
}
@article{fds311719,
Author = {Carney, CE and Edinger, JD and Krystal, AD and Stepanski, EJ and Kirby,
A},
Title = {Are insomnia patients pathologically worried or simply
worried about sleep?},
Journal = {Sleep},
Volume = {29},
Pages = {A234-A234},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2006},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000237916701066&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311719}
}
@article{fds311714,
Author = {Carney, CE and Edinger, JD and Krystal, AD and Stepanski, EJ and Kirby,
A},
Title = {The contribution of anxiety to sleep quality reporting in
insomnia subtypes},
Journal = {Sleep},
Volume = {29},
Pages = {A233-A233},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2006},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000237916701065&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311714}
}
@article{fds311688,
Author = {Rubens, R and Krystal, AD and Wessel, TC and Roth, T and Caron, J and Amato, DA},
Title = {Efficacy of eszopiclone in the treatment of sleep
maintenance insomnia},
Journal = {Neurology},
Volume = {64},
Number = {6},
Pages = {A46-A46},
Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
Year = {2005},
Month = {March},
ISSN = {0028-3878},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000227841500154&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311688}
}
@article{fds311692,
Author = {Wessel, TC and Roth, T and Krystal, AD and Caron, J and Amato,
DA},
Title = {Twelve months of nightly eszopiclone treatment in patients
with chronic insomnia: Assessment of long-term efficacy and
safety},
Journal = {Neurology},
Volume = {64},
Number = {6},
Pages = {A46-A46},
Publisher = {LIPPINCOTT WILLIAMS & WILKINS},
Year = {2005},
Month = {March},
ISSN = {0028-3878},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000227841500153&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311692}
}
@article{fds311684,
Author = {Litsch, S and Michaels, C and Carney, C and Edinger, JJ and Wohlgemuth,
WK and Krystal, AD},
Title = {A pilot study of the sleep EEG power spectral effects of
relaxation training in primary insomniacs},
Journal = {Sleep},
Volume = {28},
Pages = {A255-A255},
Publisher = {OXFORD UNIV PRESS INC},
Year = {2005},
Month = {January},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000228906101269&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311684}
}
@article{fds311710,
Author = {Wohlgemuth, WK and Edinger, JD and Krystal, AD and Rice,
JR},
Title = {Behavioral insomnia therapy for patients with fibromyalgia:
An update},
Journal = {Sleep},
Volume = {26},
Pages = {A368-A368},
Publisher = {AMER ACADEMY SLEEP MEDICINE},
Year = {2003},
Month = {May},
ISSN = {0161-8105},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000182841100929&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311710}
}
@article{fds363104,
Author = {Walsh, JK and Lankford, DD and Krystal, A and Roth, T and Jochelson, P and Garber, M and Alexander, T and Burke, J},
Title = {Efficacy and tolerability of four doses of indiplon
(NBI-34060) modified-release in elderly patients with sleep
maintenance insomnia},
Journal = {Sleep},
Volume = {26},
Pages = {A78-A78},
Publisher = {AMER ACADEMY SLEEP MEDICINE},
Year = {2003},
Month = {May},
Key = {fds363104}
}
@article{fds311701,
Author = {Becker, PM and Jamieson, AO and Jewel, CE and Bogan, RK and James, DS and Sutton, JT and Corser, B and Mayleben, DW and Bernard, SH and Dinner,
DS and Emsellem, H and Knight, E and Erwin, CW and Krystal, AD and Radtke,
RA and Farrow, S and Odynski, T and Pinto, J and Steljes, D and Feldman,
NT and O'Brien, M and Fredrickson, PA and Kaplan, J and Lin, SC and Burger,
C and Fry, JM and Guilleminault, C and Black, J and Green, PM and Schmitigal, L and Gross, PT and Dignan, S and Harsh, J and Hartwig, G and Haynes, JB and Hageman, M and Porter-Shirley, K and Hertz, G and Hirshkowitz, M and Moore, CA and Iyer, V et al.},
Title = {Randomized trial of modafinil as a treatment for the
excessive daytime somnolence of narcolepsy: US Modafinil in
Narcolepsy Multicenter Study Group.},
Journal = {Neurology},
Volume = {54},
Number = {5},
Pages = {1166-1175},
Publisher = {Ovid Technologies (Wolters Kluwer Health)},
Year = {2000},
Month = {March},
ISSN = {0028-3878},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000085785700028&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Abstract = {OBJECTIVE: This is one of two separate clinical trials to
evaluate the efficacy and safety of modafinil, a novel
wake-promoting agent, in patients with excessive daytime
sleepiness (EDS) associated with narcolepsy. METHODS: In
this 9-week, randomized, placebo-controlled, double-blind,
21-center clinical trial, patients were randomized to
receive fixed daily doses of modafinil 200 mg, modafinil 400
mg, or placebo. A placebo-controlled, 2-week treatment
discontinuation phase was included to evaluate the effects
of withdrawal on patients who had been receiving modafinil.
A total of 271 patients who were naive to modafinil received
study medication in the 9-week trial and 240 patients
received study medication in the discontinuation phase.
RESULTS: Treatment with modafinil resulted in significant
improvement in two objective measures of EDS: the Multiple
Sleep Latency Test and the Maintenance of Wakefulness Test.
Additionally, patient self-assessment of sleepiness was
significantly improved, as measured by the Epworth
Sleepiness Scale, and level of illness was significantly
reduced on the independent clinician assessment, the
Clinical Global Impression of Change. Nighttime sleep,
monitored by nocturnal polysomnography, was not adversely
effected with modafinil treatment compared with placebo
treatment. The most frequent adverse experience was
headache, which was not significantly greater for modafinil
than placebo. During treatment discontinuation, individuals
who had been receiving modafinil experienced a return of
their EDS to baseline levels. During treatment
discontinuation, patients did not experience symptoms
associated with amphetamine withdrawal syndrome. For up to 9
weeks of daily use there was no evidence for the development
of dependence at the dose levels studied. CONCLUSION: The
data indicate that modafinil has an excellent safety profile
and is very well tolerated. Modafinil is an effective
treatment for excessive daytime sleepiness in narcolepsy and
shows continued efficacy with up to 9 weeks of daily
use.},
Doi = {10.1212/wnl.54.5.1166},
Key = {fds311701}
}
@article{fds311702,
Author = {Fry},
Title = {Randomized trial of modafinil for the treatment of
pathological somnolence in narcolepsy},
Journal = {Annals of Neurology},
Volume = {43},
Number = {1},
Pages = {88-97},
Publisher = {WILEY},
Year = {1998},
Month = {January},
ISSN = {0364-5134},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000071504600011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Doi = {10.1002/ana.410430115},
Key = {fds311702}
}
@article{fds311696,
Author = {KRYSTAL, AD and WEINER, RD},
Title = {THE LARGEST LYAPUNOV EXPONENT OF THE EEG IN ECT
SEIZURES},
Journal = {Proceedings of the Conference on Measuring Chaos in the
Human Brain},
Pages = {113-&},
Publisher = {WORLD SCIENTIFIC PUBL CO PTE LTD},
Editor = {Duke, DW and Pritchard, WS},
Year = {1991},
Month = {January},
ISBN = {981-02-0701-8},
url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1991BV16W00007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92},
Key = {fds311696}
}
|
