Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis

Mol Psychiatry. 2024 Mar;29(3):750-759. doi: 10.1038/s41380-023-02366-8. Epub 2023 Dec 20.

Abstract

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 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a 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.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics / adverse effects
  • Anesthetics / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / therapy
  • Electroconvulsive Therapy* / methods
  • Female
  • Humans
  • Ketamine* / therapeutic use
  • Male
  • Network Meta-Analysis*
  • Propofol / adverse effects
  • Propofol / therapeutic use
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Ketamine
  • Propofol
  • Anesthetics