Randomized Controlled Trials of Psilocybin‐Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta‐Analysis
Vikas Menon, Parthasarathy Ramamurthy, Sandesh Venu, Chittaranjan Andrade
Acta Psychiatrica Scandinavica December 3, 2024 DOI: 10.1111/acps.13778 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 427 |
| Population | Adults with major depressive disorder (including treatment-resistant depression) in randomized controlled trials of psilocybin-assisted therapy |
| Duration | Up to 6 weeks post-intervention |
| Topics | Depression LSD Psilocybin |
| Keywords | Psilocybin therapy Psilocybin-assisted therapy Psilocybin research Psilocybin‐assisted therapy Psychedelic‐assisted therapy Treatment‐resistant depression |
| Citations | 15 |
| Key findings | Psilocybin-assisted therapy showed superior antidepressant effects compared to comparator interventions, with at least medium effect sizes lasting up to six weeks, but with increased risks of headache and dizziness. |
Abstract
ABSTRACT Introduction There is growing interest in the use of psychedelic‐assisted therapy (PAT) for major depressive disorder (MDD), including treatment‐resistant depression. We used randomized controlled trial (RCT) data to compare summary estimates of change in depression ratings with PAT versus comparator treatments in MDD. We also compared response and remission rates, and adverse effects.
Methods: We searched MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials (CENTRAL), and SCOPUS from inception till April 2024. Our primary efficacy outcome was 1‐week (or nearest) between‐group change in depression ratings. Secondary efficacy outcomes were changes in depression ratings at days 2, 14, and 42 (or nearest) and study‐defined response and remission rates at week 1 (or nearest). Safety outcomes were reported adverse effects. We pooled outcomes in random‐effects meta‐analyses using standardized mean difference (SMD; Hedges g ) for continuous outcomes and risk ratio (RR) for categorical outcomes.
Results: We found 6 eligible RCTs (pooled N = 427), all on psilocybin. The pooled SMD for 1‐week between‐group change in depression ratings was −0.72 [95% CI, −0.95 to −0.49; I 2 = 17%; 5 RCTs; n = 403], favouring PAT; results were similar at days 2, 14, and 42. The response [RR = 3.42; 95% CI, 2.35–4.97; I 2 = 0%; 4 RCTs; n = 373] and remission [RR = 3.66; 95% CI, 2.26–5.92; I 2 = 0%; 4 RCTs; n = 373] rates also favored PAT. The PAT group had a small but significantly increased risk of developing any adverse event [RR = 1.20; 95% CI, 1.01–1.42; I 2 = 43%; 4 RCTs; n = 373] and a significantly higher risk of experiencing headache [RR = 1.78; 95% CI, 1.10–2.86; I 2 = 52%; 4 RCTs; n = 373] and dizziness [RR = 6.52; 95% CI, 1.19–35.87; I 2 = 0%; 3 RCTs; n = 269]. Low heterogeneity characterized most analyses and findings were similar in sensitivity analyses.
Conclusion: Antidepressant effects of psilocybin‐assisted therapy are superior (with at least medium effect sizes) to comparator interventions for at least up to 6 weeks postintervention.