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Meta-Analysis
. 2025 May;151(5):557-571.
doi: 10.1111/acps.13778. Epub 2024 Dec 3.

Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis

Vikas Menon  1 , Parthasarathy Ramamurthy  2 , Sandesh Venu  2 , Chittaranjan Andrade  3
Affiliations
Meta-Analysis

Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis

Vikas Menon et al. Acta Psychiatr Scand. 2025 May.

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; I2 = 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; I2 = 0%; 4 RCTs; n = 373] and remission [RR = 3.66; 95% CI, 2.26-5.92; I2 = 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; I2 = 43%; 4 RCTs; n = 373] and a significantly higher risk of experiencing headache [RR = 1.78; 95% CI, 1.10-2.86; I2 = 52%; 4 RCTs; n = 373] and dizziness [RR = 6.52; 95% CI, 1.19-35.87; I2 = 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.

Keywords: LSD; major depressive disorder; psilocybin; psilocybin‐assisted therapy; psychedelic‐assisted therapy; treatment‐resistant depression.

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References

    1. A. J. Rush, M. H. Trivedi, S. R. Wisniewski, et al., “Acute and Longer‐Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report,” American Journal of Psychiatry 163, no. 11 (2006): 1905–1917, https://doi.org/10.1176/ajp.2006.163.11.1905.
    1. R. S. McIntyre, M. Alsuwaidan, B. T. Baune, et al., “Treatment‐Resistant Depression: Definition, Prevalence, Detection, Management, and Investigational Interventions,” World Psychiatry 22, no. 3 (2023): 394–412, https://doi.org/10.1002/wps.21120.
    1. H. Cai, X. M. Xie, Q. Zhang, et al., “Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta‐Analysis of Comparative Studies,” Frontiers in Psychiatry 12 (2021): 690130, https://doi.org/10.3389/fpsyt.2021.690130.
    1. J. M. Bostwick and V. S. Pankratz, “Affective Disorders and Suicide Risk: A Reexamination,” American Journal of Psychiatry 157, no. 12 (2000): 1925–1932, https://doi.org/10.1176/appi.ajp.157.12.1925.
    1. B. W. Penninx, Y. Milaneschi, F. Lamers, and N. Vogelzangs, “Understanding the Somatic Consequences of Depression: Biological Mechanisms and the Role of Depression Symptom Profile,” BMC Medicine 11, no. 1 (2013): 129, https://doi.org/10.1186/1741‐7015‐11‐129.

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