A network meta-analysis of 35 randomized controlled trials involving 2109 participants compared electroconvulsive therapy (ECT), intravenous racemic ketamine, and repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression. No significant differences emerged in response rate, remission rate, or tolerability among the three treatments. Intravenous ketamine showed significantly higher acceptability than rTMS and ECT. The confidence in the evidence for efficacy, tolerability, and acceptability was very low, largely due to small-study bias. The authors suggest that both ketamine and rTMS may be viable alternatives to ECT, but caution that larger studies are needed to confirm these findings.
Intravenous racemic ketamine, psilocybin, and theta burst stimulation (TBS) all outperformed placebo for major depressive disorder in a network meta-analysis of 28 randomized controlled trials. Ketamine and psilocybin showed significantly greater antidepressant effects than TBS, with no differences in tolerability or acceptability compared to placebo. In periods of 1 week or less, only ketamine was significantly more effective than placebo. In periods of 4 weeks or longer, both ketamine and psilocybin were significantly better than placebo. Confidence in the evidence ranged from very low to moderate due to limited studies, especially for psilocybin, and a lack of direct comparison trials. These preliminary findings suggest ketamine and psilocybin may be more effective than TBS, with ketamine possibly offering faster onset.