For treatment-resistant major depression without psychosis, intravenous ketamine is at least as effective as electroconvulsive therapy (ECT). In a randomized trial with 403 patients, 55.4% of those receiving ketamine and 41.2% of those receiving ECT showed a 50% or greater reduction in depression scores over three weeks. ECT was linked to a notable decline in memory recall after three weeks (average decrease of 9.7 points on a memory test vs. 0.9 points with ketamine), with gradual recovery during follow-up. Quality-of-life improvements were similar between groups. Ketamine caused dissociation, while ECT led to musculoskeletal side effects.
Electroconvulsive therapy (ECT) and ketamine show similar response rates for treatment-resistant depression, but a head-to-head comparison in a large, well-powered trial has been lacking. This protocol describes a non-inferiority trial randomizing 400 patients with treatment-resistant depression to receive either ECT thrice weekly or intravenous ketamine twice weekly for 3-5 weeks. The primary outcome is the proportion of responders based on a patient-reported depression scale. The study is designed to determine whether ketamine retains at least 90% of ECT's treatment effect. Results will inform patient choice, clinical practice, and insurance policies.