Efficacy of Ketamine in Bipolar Depression: Systematic Review and Meta-analysis

J Psychiatr Pract. 2015 Nov;21(6):427-35. doi: 10.1097/PRA.0000000000000106.


Objective: To consolidate the evidence from the literature to evaluate the role of ketamine in the treatment of bipolar depression.

Methods: Major databases, including MEDLINE, EMBASE, Cochrane, and Scopus, were searched through October 2014, for studies reporting the role of ketamine in the treatment of bipolar depression. Only randomized controlled trials were included in the meta-analysis. We calculated standardized mean differences (SMDs) with SE for each study included in the meta-analysis. A random effect model was used to calculate the pooled SMDs. Heterogeneity was assessed using the Cochran Q test and I statistic.

Results: Of the 721 articles that were screened, 5 studies that enrolled a total of 125 subjects with bipolar depression (mean age, 44.6±4.3 y and 65.6% females) were included in the systematic review; 3 randomized controlled trials (69 subjects) were included in the meta-analysis. The meta-analysis showed significant improvement in depression among patients receiving a single dose of intravenous ketamine compared with those who received placebo (SMD=-1.01; 95% confidence interval, -1.37, -0.66; P<0.0001). The maximum improvement was observed 40 minutes after the ketamine infusion. No heterogeneity was observed between the studies (Cochran Q test P=0.38, I=0%). The 2 studies that were excluded from the meta-analysis also showed significant improvement in depression after ketamine therapy. Individual studies also reported improvement in anhedonia and suicidal ideation after ketamine therapy. None of the subjects had serious side effects, and the side effects were similar between the ketamine and placebo groups.

Conclusions: This study suggests that ketamine is effective in treatment-resistant bipolar depression and may reduce suicidal ideation and anhedonia.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Retracted Publication

MeSH terms

  • Adult
  • Anhedonia / drug effects*
  • Bipolar Disorder* / diagnosis
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / psychology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Humans
  • Ketamine / pharmacology*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Suicidal Ideation*
  • Treatment Outcome


  • Excitatory Amino Acid Antagonists
  • Ketamine