Psilocybin-assisted therapy for depression: A systematic review and meta-analysis

Sipan Haikazian; David C J Chen-Li; Danica E Johnson; Farhan Fancy; Anastasia Levinta; M Ishrat Husain; Rodrigo B Mansur; Roger S McIntyre; Joshua D Rosenblat

doi:10.1016/j.psychres.2023.115531

Psilocybin-assisted therapy for depression: A systematic review and meta-analysis

Psychiatry Res. 2023 Nov:329:115531. doi: 10.1016/j.psychres.2023.115531. Epub 2023 Oct 11.

Authors

Sipan Haikazian¹, David C J Chen-Li¹, Danica E Johnson¹, Farhan Fancy¹, Anastasia Levinta², M Ishrat Husain³, Rodrigo B Mansur⁴, Roger S McIntyre⁵, Joshua D Rosenblat⁶

Affiliations

¹ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
² Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada.
⁶ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: joshua.rosenblat@uhn.ca.

PMID: 37844352
DOI: 10.1016/j.psychres.2023.115531

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.

Keywords: Life-threatening cancer; Major depressive disorder; Mood disorders; Psychedelic-assisted therapy; Psychedelics.

Publication types

Meta-Analysis
Systematic Review
Review
Research Support, Non-U.S. Gov't

MeSH terms

Antidepressive Agents / therapeutic use
Depression / drug therapy
Depressive Disorder, Major* / drug therapy
Hallucinogens* / pharmacology
Hallucinogens* / therapeutic use
Humans
Psilocybin / pharmacology
Psilocybin / therapeutic use
Psychotherapy / methods

Substances

Psilocybin
Antidepressive Agents
Hallucinogens

Grants and funding

CIHR/Canada