Ketamine for bipolar depression: a systematic review

This review (2021; s=6; n=135) found that ketamine (35mg/70kg; 1-6 doses) achieved a response (>50% reduction) on a score of depression for 61% of those suffering from bipolar depression (BD), compared to 5% for placebo.


Background: Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, the efficacy in bipolar depression is less clear.

Objectives: This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression.

Methods: We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since database inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies.

Findings: We identified six studies, with 135 participants (53% female, 44.7 years, SD 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from one to six; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well-tolerated; however, two participants (one receiving ketamine and one receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in two trials.

Conclusions: There is some preliminary evidence for intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.”

Authors: Anees Bahji, Carlos A. Zarate & Gustavo H. Vazquez

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Ketamine for bipolar depression: a systematic review

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Published in
International Journal of Neuropsychopharmacology
April 30, 2021
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