Classic serotonergic psychedelics for mood and depressive symptoms: a meta-analysis of mood disorder patients and healthy participants

Nicole L. Galvão-Coelho*, Wolfgang Marx, Maria Gonzalez, Justin Sinclair, Michael de Manincor, Daniel Perkins, Jerome Sarris

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

25 Citations (Scopus)

Abstract

Rationale: Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option. Objective: We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately). Results: Our search revealed 12 eligible studies (n = 257; 124 healthy participants, and 133 patients with mood disorders), with data from randomized controlled trials involving psilocybin (n = 8), lysergic acid diethylamide ([LSD]; n = 3), and ayahuasca (n = 1). The meta-analyses of acute mood outcomes (3 h to 1 day after treatment) for healthy volunteers and patients revealed improvements with moderate significant effect sizes in favor of psychedelics, as well as for the longer-term (16 to 60 days after treatments) mood state of patients. For patients with mood disorder, significant effect sizes were detected on the acute, medium (2–7 days after treatment), and longer-term outcomes favoring psychedelics on the reduction of depressive symptoms. Conclusion: Despite the concerns over unblinding and expectancy, the strength of the effect sizes, fast onset, and enduring therapeutic effects of these psychotherapeutic agents encourage further double-blind, placebo-controlled clinical trials assessing them for management of negative mood and depressive symptoms.

Original languageEnglish
Pages (from-to)341-354
Number of pages14
JournalPsychopharmacology
Volume238
Issue number2
DOIs
Publication statusPublished - Feb 2021
Externally publishedYes

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