Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder
This open-label study (n=34) investigated the effects of ketamine (35mg/70kg) on suicidal ideation and sleep rhythm in patients with (bipolar) depression and found that patients with less post-infusion nocturnal wakefulness exhibited an antisuicidal response to ketamine, compared to patients who were wakeful at night and continued suicidal ideation.
Authors
- Carlos Zarate
- Evan Ballard
- David Luckenbaugh
Published
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.
Research Summary of 'Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder'
Introduction
Vande Voort and colleagues frame the study within the substantial public-health burden of suicide and the limited pharmacologic options known to reduce suicide risk. They note that disrupted sleep, particularly difficulty maintaining sleep, is consistently associated with increased suicidal thoughts and death by suicide, and that most prior work has relied on self-report rather than objective measures such as nighttime electroencephalography (EEG). The introduction also observes that although ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to produce rapid reductions in suicidal ideation, the biological mechanisms underlying this antisuicidal effect are unknown. This study therefore set out to test whether objective changes in nocturnal wakefulness (EEG-verified minutes awake during the night) are associated with an antisuicidal response to a single subanesthetic ketamine infusion in patients with treatment-resistant major depressive disorder or bipolar depression who had baseline suicidal ideation. The investigators focused on hourly wakefulness between midnight and 04:59 AM because earlier work from their group and epidemiologic data suggested this time window is particularly relevant to suicide risk.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Vande Voort, J. L., Ballard, E. D., Luckenbaugh, D. A., Bernert, R. A., Richards, E. M., Niciu, M. J., Park, L. T., Machado-Vieira, R., Duncan, W. C., & Zarate, C. A. (2017). Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder. The Journal of Clinical Psychiatry, 78(8), 1068-1074. https://doi.org/10.4088/jcp.15m10440
References (4)
Papers cited by this study that are also in Blossom
Ionescu, D. F., Vande Voort, J. L., Niciu, M. J. et al. · Journal of Psychiatric Research (2014)
Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)
Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
Ballard, E. D., Luckenbaugh, D. A., Walls, T. S. et al. · Journal of Psychiatric Research (2015)
Cited By (6)
Papers in Blossom that reference this study
Ballard, E. D., Greenstein, D., Reiss, P. T. et al. · Translational Psychiatry (2024)
Nikkheslat, N. · Brain Behavior and Immunity - Health (2021)
Ballard, E. D., Fields, J., Farmer, C. A. et al. · Suicide and Life-Threatening Behavior (2021)
Zheng, W., Zhou, Y-L., Wang, C-Y. · Journal of Psychopharmacology (2019)
Zheng, W., Zhou, Y-L., Liu, W. et al. · Journal of Psychiatric Research (2018)
Su, T. P., Chen, M. H., Li, C. T. et al. · Neuropsychopharmacology (2017)
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