Ketamine therapy treatment of major depressive episodes: a systematic review

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine therapy in the rapid treatment of major depressive episodes

There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. In this systematic review, the trials aimed to assess the efficacy of ketamine therapy in major depressive episodes…

The meta-analysis suggests that single administrations of ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. With that said, additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.


According to WHO (2008), Major depressive disorder (MDD) and bipolar disorder (BD) are major sources of global disability. These disorders are usually chronic and characterized by relapsing remitting courses and significant impairment persisting even during periods of re-mission (Fagiolini et al. 2005; Conradi et al. 2011).

Ketamine is an NMDA receptor antagonist that has been the focus of significant clinical, research, and media interest. Since the initial report by Berman et al. (2000), ketamine produces a rapid and marked antidepressant effect, and there have been several efforts to replicate and extend this finding (aan hetRot et al. 2012).  Indeed, there have been several trials in both major depressive disorders and bipolar disorders, but this literature is disparate, predominantly characterized by small sample sizes and involves several methodological variations.


The purpose of this systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials is to assess the efficacy of ketamine in the treatment of major depressive episodes. And, In order to maximize the clinical relevance of these findings, the study focuses on clinical remission and response, but also examines changes in clinician-rated depression scores to allow meaningful comparison of the efficacy in major depression disorders and bipolar disorders.

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 2015 Mar;45(4):693-704. doi: 10.1017/S0033291714001603. Epub 2014 Jul 10.

McGirr A1Berlim MT2Bond DJ3Fleck MP4Yatham LN1Lam RW1.

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