Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder

Abstract

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.

Trial registration: ClinicalTrials.gov identifier: NCT00088699.

Conflict of interest statement

Potential conflicts of interest: All other authors have no conflict of interest to disclose, financial or otherwise.

© Copyright 2016 Physicians Postgraduate Press, Inc.

Figures

Figure 1

Timeline for Ketamine Infusion, Assessments, and Sleep Studiesa aParticipants completed an adaptation sleep study prior to their first recorded polysomnography (PSG), which occurred the night before the ketamine infusion. A second recorded PSG was done the night after the ketamine infusion. Ratings were taken 60 minutes before ketamine infusion and then again 24 hours later.

Figure 2

Relationship Between Wakefulness From 12:00–4:59 am and Antisuicidal Response to Ketaminea aEach line represents the wakefulness pattern of 1 participant. Parts A and C show baseline minutes awake recorded from the baseline sleep study (ie, night before ketamine) in participants who did (A) and did not (C) have an antisuicidal response to ketamine. Parts B and D show minutes awake recorded from the second sleep study (ie, night after ketamine) in participants who did (B) and did not (D) have an antisuicidal response to ketamine. Part E shows minutes awake recorded in a sample of healthy controls who did not receive ketamine.

Figure 3

Average Wakefulness in Suicide Responders, Nonresponders, and Healthy Controlsa aMean and standard error for wakefulness-by-hour for the night following ketamine infusion in participants with and without an antisuicidal response to ketamine. The wakefulness of the healthy control sample (n = 22) is shown as a comparison group.