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Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis.

Yazen Alnefeesi, David C J Chen-Li, Ella Krane, Muhammad Youshay Jawad, Nelson B Rodrigues, Felicia Ceban, Joshua D. Di Vincenzo, Shakila Meshkat, R. Ho, Hartej Gill, Kayla M Teopiz, Bing Cao, Yena Lee, Roger S McIntyre, Joshua D. Rosenblat

Journal of Psychiatric Research May 1, 2022 DOI: 10.1016/j.jpsychires.2022.04.037 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Randomized Peer reviewed
Sample size 2,665
Population Patients with treatment-resistant depression
Topics Depression Esketamine Ketamine
Citations 177
Key findings Ketamine produces a substantial antidepressant effect in real-world treatment-resistant depression, with 45% responding and 30% remitting, and the effect does not diminish with repeated treatments.

Abstract

Ketamine is a promising therapeutic option in treatment-resistant depression (TRD). The acute efficacy of ketamine in TRD has been demonstrated in replicated randomised-controlled trials (RCTs), but the generalizability of RCT data to real-world practice is limited. To this end, we conducted a systematic review (Search date: 25/12/2021; 1482 records identified) and meta-analysis of studies evaluating the real-world clinical effectiveness of ketamine in TRD patients. Four overlapping syntheses (Total n = 2665 patients; k = 79 studies) and 32 meta-regressions (Total n = 2050; k = 37) were conducted. All results suggest that the mean antidepressant effect is substantial (mean ± 95% CI, % responded = 45 ± 10%; p< 0.0001, % remitted = 30 ± 5.9%; p< 0.0001, Hedges g of symptomatological improvement = 1.44 ± 0.609; p < 0.0001), but the effect varies considerably among patients. The more treatment-resistant cases were found to remit less often (p < 0.01), but no such effect on response was evident (p > 0.05). Meta-regressions also confirmed that the therapeutic effect does not significantly decline with repeated treatments (p > 0.05). These results demonstrate that even the most treatment-resistant patients may benefit from ketamine, and that mid-to-long term treatment is effective in many patients.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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