Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis

Gen Hosp Psychiatry. 2015 Mar-Apr;37(2):178-84. doi: 10.1016/j.genhosppsych.2015.01.003. Epub 2015 Jan 15.


Objective: Given the significant disability, morbidity and mortality associated with depression, the promising recent trials of ketamine highlight a novel intervention. A meta-analysis was conducted to assess the efficacy of ketamine in comparison with placebo for the reduction of depressive symptoms in patients who meet criteria for a major depressive episode.

Method: Two electronic databases were searched in September 2013 for English-language studies that were randomized placebo-controlled trials of ketamine treatment for patients with major depressive disorder or bipolar depression and utilized a standardized rating scale. Studies including participants receiving electroconvulsive therapy and adolescent/child participants were excluded. Five studies were included in the quantitative meta-analysis.

Results: The quantitative meta-analysis showed that ketamine significantly reduced depressive symptoms. The overall effect size at day 1 was large and statistically significant with an overall standardized mean difference of 1.01 (95% confidence interval 0.69-1.34) (P<.001), with the effects sustained at 7 days postinfusion. The heterogeneity of the studies was low and not statistically significant, and the funnel plot showed no publication bias.

Conclusions: The large and statistically significant effect of ketamine on depressive symptoms supports a promising, new and effective pharmacotherapy with rapid onset, high efficacy and good tolerability.

Keywords: Depression; Ketamine; Meta-analysis; Therapy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Bipolar Disorder / drug therapy*
  • Depressive Disorder, Major / drug therapy*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*


  • Excitatory Amino Acid Antagonists
  • Ketamine