Ketamine for Bipolar Depression: A Systematic Review

Summary

Ketamine appears to help treat bipolar depression, though evidence is preliminary. A systematic review of six studies involving 135 adults (53% female, average age 44.7 years) found that 61% of those receiving intravenous racemic ketamine (0.5 mg/kg, added to a mood stabilizer) achieved at least a 50% reduction in depression severity, compared to 5% receiving placebo. Response rates across studies ranged from 52% to 80%. Ketamine was reasonably well tolerated, but two participants developed manic symptoms (one on ketamine, one on placebo), and some experienced significant dissociative symptoms 40 minutes after infusion in two trials. Longer-term outcomes and alternative formulations need further study.

Study at a glance

Abstract

Abstract Background Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. 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 each database’s inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies. Results We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; 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, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials. Conclusions There is some preliminary evidence supporting use of 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.