Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial
This double-blind, randomised, crossover, placebo-controlled replication study (n=15) investigated the effects of ketamine (35mg) on patients with treatment-resistant bipolar depression, and found rapid improvements of depressive symptoms, suicidal ideation, and subjective well-being within 40 minutes after infusion and up to 3 days after.
Authors
- Carlos Zarate
- David Luckenbaugh
- Nancy Elizabeth Brutsche
Published
Abstract
Introduction
Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample.
Methods
In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion.
Results
Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point.
Discussion
This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
Research Summary of 'Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial'
Introduction
Bipolar disorder is a severe and often lethal psychiatric illness for which existing pharmacological treatments do not typically produce rapid reductions in depressive symptoms or suicidal ideation within hours or a few days. Converging preclinical, postmortem, and clinical evidence has implicated glutamatergic neurotransmission and the NMDA receptor complex in mood disorders, and prior clinical trials in major depressive disorder (MDD) have shown that a single intravenous infusion of the NMDA antagonist ketamine can produce rapid antidepressant effects. Earlier work by the same group reported rapid antidepressant effects of ketamine in a small sample of treatment-resistant bipolar depression. Zarate and colleagues designed the present study to replicate that earlier finding in an independent sample of inpatients with bipolar I or II depression who were maintained on therapeutic lithium or valproate. The primary hypothesis was that a single intravenous infusion of ketamine (.5 mg/kg) would produce a rapid and clinically meaningful reduction in depressive symptoms within 230 minutes postinfusion, with secondary interest in effects on suicidal ideation and safety/tolerability.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Zarate, C. A., Brutsche, N. E., Ibrahim, L., Franco-Chaves, J., Diazgranados, N., Cravchik, A., Selter, J., Marquardt, C. A., Liberty, V., & Luckenbaugh, D. A. (2012). Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial. Biological Psychiatry, 71(11), 939-946. https://doi.org/10.1016/j.biopsych.2011.12.010
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