Ketamine and esketamine are effective, safe, and acceptable treatments for depression. A meta-analysis of 36 randomized controlled trials (2,903 participants, 57% female, average age 45 years) found that treatment with either form of ketamine improved response (2.14 times more likely), remission (1.64 times more likely), and depression severity compared to placebo. There was no difference in treatment retention, dropouts due to adverse events, or overall number of adverse events between ketamine and placebo.
A systematic review and meta-analysis of 18 studies found that psychedelic-assisted therapies—psilocybin, LSD, MDMA, and ayahuasca—were well tolerated and produced large reductions in depression symptoms across various diagnoses. Psilocybin showed a large effect (standardized mean difference -1.92) and MDMA a moderate-to-large effect (standardized mean difference -0.71). However, the certainty of the evidence was low to very low due to small sample sizes, blinding issues, study heterogeneity, and publication bias. The results are promising but highlight the need for larger, more rigorous studies.