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Meta-Analysis
. 2023 Feb 1:322:194-204.
doi: 10.1016/j.jad.2022.09.168. Epub 2022 Oct 7.

Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis

Kwonmok Ko  1 , Emma I Kopra  2 , Anthony J Cleare  3 , James J Rucker  3
Affiliations
Meta-Analysis

Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis

Kwonmok Ko et al. J Affect Disord. .

Erratum in

Abstract

Background: Psychedelic therapy shows promise for Major Depressive Disorder, especially when treatment-resistant, as well as life-threatening illness distress. The objective of this systematic review, inclusive of meta-analysis, is to examine recent clinical research on the therapeutic effects of classic psychedelics on depressive symptoms.

Methods: Fourteen psychedelic therapy studies, utilising psilocybin, ayahuasca, or LSD, were systematically reviewed. For the meta-analysis, standardised mean differences were calculated for seven randomised controlled trials.

Results: The systematic review indicated significant short- and long-term reduction of depressive symptoms in all conditions studied after administration of psilocybin, ayahuasca, or LSD, with psychological support. In the meta-analysis, symptom reduction was significantly indicated in three timepoints out of four, including 1-day, 1-week, and 3-5 weeks, supporting the results of the systematic review, with the exception of the 6-8 weeks follow-up point which was less conclusive.

Limitations: The absence of required data for 2 studies necessitated the less precise use of graphical extraction and imputation. The small sample size in all but one study negatively affected the statistical power. None of the studies had long-term follow-up without also utilising the cross-over method, which did not allow for long-term results to be included in the meta-review.

Conclusions: This review indicates an association between psychedelic therapy and significant reduction of depressive symptoms at several time points. However, the small number of studies, and low sample sizes, calls for careful interpretation of results. This suggests the need for more randomised clinical trials of psychedelic therapy, with larger and more diverse samples.

Keywords: Ayahuasca; Depression; Illness-related distress; LSD; Psilocybin; Psychedelic therapy.

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Conflict of interest statement

Conflict of interest KK and EIK are both PhD students and members of Psychoactive Trials Group [PTG] at King's College London [KCL]. KCL receives grant funding from COMPASS Pathways PLC and Beckley PsyTech to undertake phase 1 and phase 2 trials with psychedelics, including psilocybin. JJR is an honorary consultant psychiatrist at The South London & Maudsley NHS Foundation Trust [SLaM, NHS UK], a consultant psychiatrist at Sapphire Medical Clinics and an NIHR Clinician Scientist Fellow at the Centre for Affective Disorders at King's College London. JR leads PTG at KCL, with the same potential conflict of interest as above; COMPASS Pathways PLC has paid for JJR to attend trial related meetings and conferences to present the results of research using psilocybin. JJR has undertaken paid consultancy work for Beckley PsyTech, Delica Therapeutics and Clerkenwell Health. AJC is employed by KCL and is an honorary consultant for SLaM (NHS UK). He has recently received honoraria for presentations and/or serving on advisory boards from the following pharmaceutical companies: Janssen, Lundbeck, Allergan, and Livanova. Additionally, he is supported by the NIHR Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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