Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-on Trial
By C. Zarate, N. Brutsché, Lobna A Ibrahim, José A. Franco-Chaves, N. Diazgranados, A. Cravchik, J. Selter, Craig A. Marquardt, Victoria Liberty, D. Luckenbaugh. Biological Psychiatry, 2012
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Background 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 (NMDA) 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 (0.5 mg/kg) or placebo on two test days two weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS), which was used to rate overall depressive symptoms at baseline, at 40, 80, 110, and 230 minutes post-infusion, and on Days 1, 2, 3, 7, 10, and 14 post-infusion. Results Within 40 minutes, depressive symptoms as well as suicidal ideation significantly improved in subjects receiving ketamine compared to placebo (d=0.89, 95% C.I. = 0.61–1.16 and 0.98, 95% C.I. = 0.64–1.33, 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. Conclusion 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.
Subfields: Biological Psychiatry, Pharmacology, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/bb7cb479d63712fe872cd02bced766ce1447ad81
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Citations in the corpus
- Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression (2012, positive): “A recent study of a single ketamine infusion in bipolar depression found a time to relapse of just two days using the Kaplan-Meier method (11).”
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) (2013, background): “Studies clearly showed ketamine antidepressive properties [64–66], with a rapid resolution of suicidal ideation, even during bipolar disorder [64,67].”