Ketamine vs Electroconvulsive Therapy for Major Depressive Episode

Electroconvulsive therapy (ECT) appears more effective than ketamine for treating major depressive episodes in adults, though the evidence is limited by small studies. A meta-analysis of five randomized trials (141 ketamine patients, 137 ECT patients) found ECT produced significantly higher response and remission rates one week after treatment. ECT was 27% more likely to achieve response and 43% more likely to achieve remission than ketamine. In methodologically stronger trials, ECT showed a moderate advantage over ketamine on depression rating scales. No significant differences emerged between treatments for number of sessions needed or cognitive side effects. The authors caution that conclusions are tempered by the small number and size of existing trials.

Study at a glance

Abstract

ImportanceThe relative efficacy of ketamine and electroconvulsive therapy (ECT) in adults with major depressive episode (MDE) needs clarification.ObjectiveTo compare depression rating outcomes with ketamine vs ECT in adults with MDE and to compare response and remission rates, number of sessions to response and remission, and adverse effects.Data SourcesTwo investigators independently systematically searched MEDLINE, ScienceDirect, and Google Scholar databases using a combination of relevant Medical Subject Headings terms and free-text keywords from database inception through May 15, 2022, to identify relevant English-language trials.Study SelectionParallel-group randomized clinical trials (RCTs).Data Extraction and SynthesisTwo investigators independently extracted data and assessed risk of bias. One-week posttreatment outcomes were pooled as standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes in random-effects meta-analyses.Main Outcomes and MeasuresEfficacy outcomes were 1-week (or nearest) posttreatment depression ratings, 1-week (or nearest) study-defined response and remission rates, and number of sessions to treatment response and remission. Safety outcomes were reported adverse effects.ResultsFive trials (ketamine group: n = 141; ECT group: n = 137) were meta-analyzed. The overall pooled SMD for posttreatment depression ratings was −0.39 (95% CI, −0.81 to 0.02; I2 = 45%; 5 RCTs). For this efficacy outcome, in a sensitivity analysis of methodologically stronger trials, ECT was superior to ketamine (SMD, −0.45; 95% CI, −0.75 to −0.14; I2 = 6%; 2 RCTs). ECT was also superior to ketamine for study-defined response (RR, 1.27; 95% CI, 1.06-1.53; I2 = 0%; 3 RCTs) and remission (RR, 1.43; 95% CI, 1.12-1.82; I2 = 0%; 2 RCTs) rates. No significant differences were noted between groups for number of sessions to response and remission and for cognitive outcomes. Key limitations were small number of studies, limited sample size, and high risk of bias in all trials.Conclusion and RelevanceThe findings of this systematic review and meta-analysis suggest an efficacy advantage for ECT over ketamine in adults with MDE. These conclusions are tempered by the small number and size of existing trials.