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.
A meta-analysis of six randomized controlled trials (total 427 participants) found that psilocybin-assisted therapy produced significantly greater reductions in depression ratings than comparator treatments for major depressive disorder, including treatment-resistant depression. The effect was medium to large (standardized mean difference −0.72) at one week and persisted through six weeks. Response and remission rates were roughly 3.4 to 3.7 times higher with psilocybin therapy. However, the therapy carried a small increased risk of any adverse event, particularly headache and dizziness. Low heterogeneity across studies supports the reliability of these findings.
In outpatients with treatment-resistant depression, oral ketamine was better tolerated than intravenous (IV) ketamine, with a lower dropout rate (26.7% vs 54.8%). Depression ratings and response and remission rates did not differ between the two groups at day 14 or day 30. Adverse events such as headache (56.7% vs 74.2%) and drowsiness (0.0% vs 22.6%) were less common with oral ketamine. However, conclusions about relative antidepressant efficacy cannot be drawn due to the high dropout rate in the IV group.