• Anees Bahji, Gustavo H Vazquez, and Carlos A Zarate.
• Department of Psychiatry, Queen's University, Kingston, ON, Canada; Department of Public Health Sciences, Queen's University, Kingston, ON, Canada.
• J Affect Disord. 2021 Jan 1; 278: 542-555.

BackgroundKetamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear.ObjectivesThis study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.DesignSystematic review and meta-analysis.Data SourcesWe searched PubMed, MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for relevant studies published since database inception and December 17, 2019.Study Eligibility CriteriaWe considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression.OutcomesPrimary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events.AnalysisEvidence from randomized controlled trials was synthesized as rate ratios (RRs) for treatment response, disorder remission, adverse events, and withdrawals and as standardized mean differences (SMDs) for change in symptoms, via random-effects meta-analyses.Findings24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37).ConclusionsIntravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.Copyright © 2020. Published by Elsevier B.V.

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