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A systematic review and meta-analysis of the efficacy of ketamine compared to electroconvulsive therapy for treatment-resistant depression.

Guoguang Song, Ugwah-Oguejiofor Chinenye Jane

International Journal of Psychiatry in Clinical Practice March 2026 DOI: 10.1080/13651501.2025.2576205 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Randomized Peer reviewed
Sample size 676
Population Patients with treatment-resistant major depressive disorder
Interventions Ketamine Electroconvulsive therapy (ECT)
Measures MADRS
Topics Depression Ketamine Esketamine
Keywords Adverse event Electroconvulsive therapy Remission Response to treatment
Key findings Across six pooled studies, ketamine infusion and ECT did not differ significantly in treatment response, MADRS scores, remission, relapse, or adverse events. The authors suggest ketamine is not inferior to ECT for treatment-resistant major depression, while calling for further validation.

Abstract

Electroconvulsive therapy (ECT) has long been considered the main method of treatment for patients with resistant major depressive disorder (MDD). Recent studies have shown that ketamine infusion can also effectively improve treatment-resistant MDD. Thus, we conducted this meta-analysis to compare the efficacy of ketamine with ECT for treating treatment-resistant depression. We systematically searched PubMed, the Cochrane Library, Scopus and Web of Science from the inception to 2 October 2024, to identify clinical trials and randomised controlled trials comparing the effect of ketamine with ECT on treatment-resistant major depression. Six studies with 353 individuals in the ketamine group and 323 individuals in the ECT group were included. No significant differences were observed between ECT and ketamine in terms of response to treatment (RR 1.03, 95% CI (0.78, 1.37), I2 = 77.14%, T2 = 0.08), MADRS score (weighted mean difference (WMD) 0.98, 95% CI (-5.04, 7.00), I2 = 94.74%, T2 = 26.52), remission (RR 0.65, 95% CI (0.16, 2.64), I2 = 89.77%, T2 = 1.19), relapse (RR 0.93, 95% CI (0.50, 1.72), I2 = 20.13%, T2 = 0.04) and the number of those experiencing adverse events (RR 0.72, 95% CI (0.47, 1.10), I2 = 0.00%, T2 = 0.00). These findings suggest that ketamine is not inferior to ECT for treating MDD; however, future studies are needed for validation.

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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Depression Ketamine Esketamine

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