Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis

• Published in: Journal of affective disorders 2021-01, Vol.278, p.542-555
• Main Authors: Bahji, Anees, Vazquez, Gustavo H., Zarate, Carlos A.
• Format: Article
• Language: English
• Subjects: Antidepressive Agents - therapeutic use; Bipolar disorder; Depression; Depressive disorder; Depressive Disorder, Major - drug therapy; Esketamine; Humans; Ketamine; Ketamine - adverse effects; Major; Meta-analysis; Randomized controlled trials
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2020.09.071

•We reviewed the peer-reviewed academic literature to synthesize evidence for the comparative efficacy and acceptability of racemic ketamine and esketamine.•24 randomized controlled trials were identified and data across studies were pooled by way of systematic review and meta-analysis.•24 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).•Racemic ketamine appears to be more efficacious than esketamine for the treatment of depression. Head to head comparisons are needed to confirm the present findings. Ketamine 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. This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression. Systematic review and meta-analysis. We 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. We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression. Primary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events. Evidence 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. 24 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). Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.