Psilocybin-assisted therapy for depression: A systematic review and meta-analysis
This systematic review analyzed the effects of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. The review included 13 studies with a total of 686 participants, and the meta-analysis of 9 studies (596 participants) found a significant and large effect in favor of psilocybin (SMD = -0.78; p<0.001) for reducing depressive symptoms. The review suggests preliminary evidence supporting the antidepressant efficacy of psilocybin-assisted psychotherapy but calls for further studies to assess safety, efficacy, and treatment optimization.
Authors
- Roger McIntyre
- Jonathan Rosenblat
- Rodrigo Mansur
Published
Abstract
The aim of this review was to determine the effect of psilocybin on depressive symptoms in patients diagnosed with life-threatening illnesses or major depressive disorder. Systematic searches were conducted to search for randomized clinical trials and open-label trials that evaluated depression symptoms after psilocybin therapy. Data was pooled using a random-effects model. The primary outcome was the standardized mean difference (SMD) in depression severity, determined by calculating the change in depression ratings from baseline to the primary endpoint in the psilocybin arm versus the control arm. The literature search yielded 1734 studies, and 13 studies (n = 686) were included in either qualitative and/or quantitative analyses. The meta-analysis included 9 studies (pooled n = 596) and yielded a large effect size in favour of psilocybin (SMD = -0.78; p<0.001). Risk ratios for response and remission were large and significant in favour of psilocybin. A review of open-label trials showed robust decreases in depressive symptoms following psilocybin administration. These findings provide preliminary evidence for antidepressant efficacy with psilocybin-assisted psychotherapy, however, further studies are needed to evaluate safety and efficacy and to optimize treatment protocols.
Research Summary of 'Psilocybin-assisted therapy for depression: A systematic review and meta-analysis'
Introduction
Depression is a common, disabling disorder with high lifetime prevalence and substantial relapse and non-adherence rates to conventional antidepressants. Renewed interest in serotonergic psychedelics such as psilocybin has followed promising early research and several recent randomized controlled trials (RCTs) showing reductions in depressive and anxiety symptoms. However, the optimal dosing regimen for psilocybin in depressive disorders — and how dose relates to both efficacy and adverse events across different patient groups — remains unclear. Perez and colleagues therefore undertook a systematic review and dose-response meta-analysis of double-blind, randomized, placebo-controlled fixed-dose trials of psilocybin in adults with primary or secondary depression. The primary objective was to characterise the dose-response relationship for reduction in depressive symptoms and to estimate near-maximum effective doses (ED50 and ED95). Secondary objectives included examining dose-response relations for anxiety outcomes and for adverse events, to inform optimal dosing that balances efficacy and tolerability.
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Study Details
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Haikazian, S., Chen-Li, D. C., Johnson, D. E., Fancy, F., Levinta, A., Husain, M. I., Mansur, R. B., McIntyre, R. S., & Rosenblat, J. D. (2023). Psilocybin-assisted therapy for depression: A systematic review and meta-analysis. Psychiatry Research, 329, 115531. https://doi.org/10.1016/j.psychres.2023.115531
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