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

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.