Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.

ObjectiveTo determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.Data synthesis and study qualityInformation on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges’ g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies’ sample sizes. Study quality was appraised using Cochrane’s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.Eligibility criteriaRandomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.ResultsMeta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges’ g=0.66, 95% confidence interval (CI) 0.46 to 0.86, P