Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions: A Systematic Review and Meta-Analysis

Psychedelic-assisted therapy (PAT) was not more effective than open-label traditional antidepressants (TADs) for treating major depression when trials are compared under equal unblinding conditions. A systematic review and meta-analysis included 24 trials from a PubMed search (March 2024) and evaluated change on the 17-item Hamilton Depression Rating Scale. The analysis found no statistically significant difference between PAT and open-label TADs, with an estimated effect difference of 0.3 favoring open-label TADs (P = .73). The study also assessed potential unblinding and blinding integrity effects. Blinding appeared to matter for TADs (open-label TAD outcomes better than blinded TAD outcomes; P = .04), but the comparable difference was not observed for PAT, consistent with PAT trials being effectively open label. Overall findings challenge highly optimistic narratives about PAT effectiveness and emphasize the role of blinding integrity.