Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions
JAMA Psychiatry March 18, 2026 Zachary J. Williams, Hannah Barnett, Balázs Szigeti 10 citations
In trials for major depression, psychedelic-assisted therapy (PAT) was no more effective than open-label traditional antidepressants (TADs) such as SSRIs and SNRIs. Across 8 PAT trials (249 patients) and 16 open-label TAD trials (7921 patients), the estimated difference in symptom improvement was 0.3 favoring TADs, a statistically non-significant result. Open-label TADs outperformed blinded TAD treatment, but PAT showed no such difference, confirming that PAT trials are effectively always open label. These findings challenge overly optimistic claims about PAT and underscore the importance of maintaining blinding integrity in clinical research.