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Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis

Otto Simonsson, Per Carlbring, Robin Carhart-Harris, Alan K. Davis, David Nutt, Roland R. Griffiths, David Erritzøe, Simon B. Goldberg

Psychiatry Research July 23, 2023 DOI: 10.1016/j.psychres.2023.115349 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Peer reviewed
Sample size 102
Population Participants in psilocybin trials for depression
Interventions psilocybin escitalopram waitlist
Dose two-dose
Topics Depression Psilocybin
Keywords Meta-analysis Psilocybin therapy Clinical depression treatment Psychedelic medicine Mental health research Therapeutic efficacy
Citations 24
Key findings Clinically significant symptom worsening occurred for about 10% of participants in the psilocybin and escitalopram conditions and for 63.6% in the waitlist condition, with psilocybin showing a lower likelihood of worsening versus waitlist and no difference versus escitalopram.

Abstract

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for depression, most cited first.

Study Year Design Participants
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188
The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression 2020 Meta-analysis n = 117
Psychedelics in the treatment of unipolar mood disorders: a systematic review Patients with broadly defined unipolar mood disorders 2016 Systematic review n = 423
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Patients with life-threatening diseases and symptoms of anxiety or depression 2018 Systematic review n = 445

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