Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 39627679 · doi:10.1111/acps.13778
What was done
Authors searched MEDLINE, EMBASE, Cochrane CENTRAL, and SCOPUS through April 2024 for randomized controlled trials (RCTs) evaluating psychedelic-assisted therapy against comparator treatments in major depressive disorder. The primary efficacy outcome was 1-week between-group change in depression ratings using standardized mean difference (SMD, Hedges g). Secondary outcomes included depression rating changes at days 2, 14, and 42, study-defined response and remission rates at week 1 (risk ratio, RR), and adverse effects. Random-effects meta-analyses were used to pool outcomes.
What was found
Six RCTs met inclusion criteria (pooled N = 427), all evaluating psilocybin: - 1-week depression rating reduction favored psilocybin: SMD -0.72 (95% CI -0.95 to -0.49; I2 = 17%; 5 RCTs, n = 403), with similar effects at days 2, 14, and 42. - 1-week response rate favored psilocybin: RR 3.42 (95% CI 2.35 to 4.97; I2 = 0%; 4 RCTs, n = 373). - 1-week remission rate favored psilocybin: RR 3.66 (95% CI 2.26 to 5.92; I2 = 0%; 4 RCTs, n = 373). - Adverse events were significantly higher in the psilocybin group: any adverse event (RR 1.20; 95% CI 1.01 to 1.42; I2 = 43%; 4 RCTs, n = 373), headache (RR 1.78; 95% CI 1.10 to 2.86; I2 = 52%; 4 RCTs, n = 373), and dizziness (RR 6.52; 95% CI 1.19 to 35.87; I2 = 0%; 3 RCTs, n = 269).
Why it matters
This review shows that psilocybin-assisted therapy demonstrates moderate-to-large antidepressant effects and more than triples response and remission rates relative to comparators over short-to-medium follow-up.
Limits
The total evidence base is small, comprising only 6 trials and 427 participants. Outcome reporting is limited to 6 weeks postintervention, leaving long-term durability and safety unassessed. The abstract does not evaluate blinding integrity or the specific psychotherapy components delivered alongside psilocybin.
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