Efficacy and Safety of Ketamine-assisted Electroconvulsive Therapy in Major Depressive Episode: A Systematic Review and Network Meta-Analysis

OBJECTIVE: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). METHODS: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges’ g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. RESULTS: Twenty-two studies were included in the systematic review. A total of 2,322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with a propofol reference group, was −2.21 (95% confidence interval [CI], −3.79 to −0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, −0.18; 95% CI, −0.28 to −0.09). No other statistically significant differences were found. CONCLUSIONS: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.