Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up
In a randomised, waiting‑list controlled study of 27 adults with moderate–severe major depressive disorder who received two psilocybin doses with supportive psychotherapy, 24 completers showed large, durable reductions in GRID‑HAMD scores through 12 months (Cohen’s d ≈2.0–2.6), with 75% meeting response criteria and 58% achieving remission and no serious long‑term psilocybin‑related adverse events. Participant ratings of personal meaning, spiritual and mystical experience predicted increased well‑being at 12 months but did not predict antidepressant improvement.
Authors
- Roland Griffiths
- Matthew Johnson
- Alan Davis
Published
Abstract
Background
Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.
Aims
This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin.
Methods
This randomized, waiting-list controlled study enrolled 27 patients aged 21–75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose.
Results
All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression.
Conclusions
These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.
Research Summary of 'Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up'
Introduction
Major depressive disorder (MDD) is highly prevalent, recurrent, and a major cause of disability; first-line treatments often take weeks to work and many patients fail to achieve durable remission. Earlier clinical studies have reported rapid antidepressant effects after one or two doses of psilocybin administered alongside psychotherapy, but follow-up intervals in those trials were short (up to 6 months) and evidence about longer-term efficacy and safety in MDD remains limited. A recent double-blind trial comparing high-dose psilocybin with standard antidepressant treatment did not find a significant difference on its primary outcome at 6 weeks, underscoring uncertainty about comparative and sustained benefits. Davis and colleagues set out to evaluate the durability of antidepressant effects and safety of psilocybin-assisted treatment across a 12-month follow-up in adults with moderate to severe unipolar MDD. Using a randomised waitlist-controlled design in which participants received two supervised psilocybin sessions with supportive psychotherapy, the study aimed to measure clinician- and self-rated depression severity over one year, to examine whether features of the acute psilocybin experience predicted long-term outcomes, and to monitor adverse events and other safety signals.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., & Griffiths, R. R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology, 36(2), 151-158. https://doi.org/10.1177/02698811211073759
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