Five-year outcomes of psilocybin-assisted therapy for Major Depressive Disorder
Alan K. Davis, Meghan DellaCrosse, Nathan D. Sepeda, Adam W. Levin, Mary P Cosimano, Hillary Shaub, Washington Taylor, Peter M. Gooch, Shoval Gilead, Skylar J. Gaughan, Stacey B. Armstrong, Frederick S. Barrett
Journal of Psychedelic Studies September 4, 2025 DOI: 10.1556/2054.2025.00461 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Long-term follow-up of a randomized controlled trial with parallel convergent mixed methods Qualitative Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Individuals with major depressive disorder who previously participated in an RCT of psilocybin-assisted therapy |
| Intervention | Psilocybin-assisted therapy |
| Duration | Five-year follow-up |
| Topics | Depression Psilocybin |
| Keywords | Psychotherapist Clinical psychology |
| Citations | 4 |
| Key findings | Psilocybin-assisted therapy led to sustained reductions in depression over five years, with 67% of participants in remission. |
Abstract
Abstract Background Major Depressive Disorder (MDD) is a leading cause of disability and economic loss, with high recurrence and treatment resistance. Psilocybin-assisted therapy (PAT) shows promise in reducing depressive symptoms, but long-term effects are unknown. We aimed to determine the long-term safety and efficacy of PAT for MDD over a five-year follow-up period.
Methods: Individuals who previously participated in an RCT studying the effects of PAT for patients with MDD were contacted for a long-term follow-up (LTFU) study. This study uses a parallel convergent mixed methods design. Of the original 24 RCT participants, 21 enrolled in the LTFU study, with 18 (75%) completing it. For the six non-completers, baseline scores were used in quantitative analyses as conservative estimates. The primary outcome was clinician-rated change in depression severity from baseline to LTFU. Secondary outcomes included anxiety, functional impairment, and qualitative assessments of participants' experiences and mental health.
Results: Significant and sustained reductions in depression were observed, with 67% in remission for at least five years post-treatment. Anxiety and functional impairment also improved. Qualitative interviews revealed lasting positive changes in mindset, emotional health, and relationships. Participants reported enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported.
Conclusion: This study supports the long-term efficacy and safety of PAT in reducing depressive symptoms and improving mental health in patients with MDD. Further research is needed to determine if these findings can be replicated, and to explore the mechanisms behind the sustained benefits of PAT, potentially validating an approach that could transform the treatment of MDD.