Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis
This systemic review and meta-analysis (2020) of 24 clinical trials (n=1877) assessed the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression. The authors found that intravenous ketamine appeared to be more efficacious than intranasal esketamine for the treatment of depression.
Authors
- Carlos Zarate
Published
Abstract
Background
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.
Objectives
This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.
Design
Systematic review and meta-analysis.Data sources: 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.Study eligibility criteria: We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression.
Outcomes
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.
Analysis
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.
Findings
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).
Conclusions
Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.
Research Summary of 'Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis'
Introduction
Ketamine's rapid antidepressant effects at subanaesthetic doses have attracted attention as an option for treatment-resistant depression, but its dissociative effects, abuse potential and the logistical challenges of intravenous administration have prompted investigation of alternative formulations and routes. One such alternative is the S-enantiomer esketamine, which is more potent at the NMDA receptor and is available as an intranasal spray; intranasal esketamine received regulatory approval for treatment-resistant depression in 2019. Despite these developments, uncertainty remains about comparative efficacy, tolerability and acceptability between intravenous racemic (R,S)-ketamine and intranasal esketamine, and no robust head-to-head clinical trials had been completed at the time of this review. Bahji and colleagues set out to synthesise the randomised controlled trial evidence to compare racemic ketamine and esketamine for unipolar and bipolar depression. The study aimed to estimate comparative effects on remission and symptom change, to examine safety and acceptability (including all-cause and adverse-event withdrawals), and to explore moderators such as treatment resistance, trial design and mode of administration using systematic review and meta-analysis methods registered on the Open Science Framework and performed in accordance with PRISMA guidance.
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Study Details
- Study Typemeta
- Journal
- Compounds
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- APA Citation
Bahji, A., Vazquez, G. H., & Zarate, C. A. (2021). Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. Journal of Affective Disorders, 278, 542-555. https://doi.org/10.1016/j.jad.2020.09.071
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