• Carlos A Zarate, Nancy E Brutsche, Lobna Ibrahim, Jose Franco-Chaves, Nancy Diazgranados, Anibal Cravchik, Jessica Selter, Craig A Marquardt, Victoria Liberty, and David A Luckenbaugh.
• Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, Maryland, USA. zaratec@mail.nih.gov
• Biol. Psychiatry. 2012 Jun 1; 71 (11): 939-46.

BackgroundCurrently, 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.MethodsIn 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.ResultsWithin 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.ConclusionsThis 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.Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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