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Efficacy and adverse effects of ketamine versus electroconvulsive therapy for major depressive disorder: A systematic review and meta-analysis

Debora de A. Simoes Moreira, Luís Eduardo Gauer, Guilherme Teixeira, A. D. da Silva, Stefanie Cavalcanti, J. Quevedo

Journal of Affective Disorders March 1, 2023 DOI: 10.1016/j.jad.2023.02.152 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Randomized Peer reviewed
Sample size 8
Population Patients with treatment-resistant depression (TRD)
Intervention Ketamine
Topics Depression Esketamine Ketamine
Citations 25
Key findings Ketamine was not superior to ECT for reducing depressive symptoms or response rate, but was associated with a significantly lower risk of muscle pain.

Abstract

Background: ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220).

Methods: We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization’s International Clinical Trials Registry Platform, without restrictions on publication date. Selection criteria: randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD.

Results: Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = −0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02 and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed.

Limitations: Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes.

Conclusion: Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.

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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