TY - JOUR
T1 - Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder
AU - Vande Voort, Jennifer L.
AU - Ballard, Elizabeth D.
AU - Luckenbaugh, David A.
AU - Bernert, Rebecca A.
AU - Richards, Erica M.
AU - Niciu, Mark J.
AU - Park, Lawrence T.
AU - Machado-Vieira, Rodrigo
AU - Duncan, Wallace C.
AU - Zarate, Carlos A.
N1 - Funding Information:
Submitted: October 6, 2015; accepted February 11, 2016. Online first: December 6, 2016. Drug names: citalopram (Celexa and others); clozapine (Clozaril, FazaClo, and others); doxepin (Silenor and others); fluoxetine (Prozac and others); fluvoxamine (Luvox and others); ketamine (Ketalar and others); riluzole (Rilutek and others); sertraline (Zoloft and others). Potential conflicts of interest: Dr Zarate is listed as a co-inventor on a patent for the use of ketamine and its metabolites in major depression, and he has assigned his rights in the patent to the US government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise. Funding/support: Funding for this work was provided in part by the Intramural Research Program at the National Institute of Mental Health (NIMH), National Institutes of Health (NIH) (IRP-NIMH-NIH) (NCT00024635; 04-M-0222), by a NARSAD Independent Investigator to Dr Zarate, by a Brain & Behavior Mood Disorders Research Award to Dr Zarate, and by grants from the National Institutes of Health (K23MH093490) to Dr Bernert. Role of the sponsor: The NIMH, NIH, NARSAD, and the Brain & Behavior Research Foundation had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Acknowledgment: Ioline Henter, MA (NIMH) provided invaluable editorial assistance and was funded by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health.
Publisher Copyright:
© Copyright 2016 Physicians Postgraduate Press, Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Objective: Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-D-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine. Methods: Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22). Results: After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F1, 22 = 5.04, P =.04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F1, 40 = 3.15, P =.08). Conclusions: Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.
AB - Objective: Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-D-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine. Methods: Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22). Results: After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F1, 22 = 5.04, P =.04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F1, 40 = 3.15, P =.08). Conclusions: Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.
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U2 - 10.4088/JCP.15m10440
DO - 10.4088/JCP.15m10440
M3 - Article
C2 - 27929610
AN - SCOPUS:85032629845
VL - 78
SP - 1068
EP - 1074
JO - Diseases of the Nervous System
JF - Diseases of the Nervous System
SN - 0160-6689
IS - 8
ER -