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

This meta-analysis (n=102, s=3) assesses the risk of symptom worsening in psilocybin trials for depression. It reports that clinically significant symptom worsening occurred in approximately 10% of participants in the psilocybin and escitalopram conditions, and in 63.6% of participants in the waitlist condition. Psilocybin showed a lower likelihood of symptom worsening compared to waitlist, and no difference when compared to escitalopram.

Abstract of Assessing the risk of symptom worsening in psilocybin-assisted therapy (PAT) for depression

“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.”

Authors: Otto Simonsson, Per Carlbring, Robin Carhart-Harris, Alan K. Davis, David J. Nutt, Roland R. Griffiths, David Erritzoe & Simon B. Goldberg

Summary of Assessing the risk of symptom worsening in psilocybin-assisted therapy (PAT) for depression

The leading factor contributing to disability worldwide is depression, and standard treatments are effective for some patients. Still, many do not respond to treatment at all, and some experience worsening depressive symptoms. Psilocybin-assisted therapy shows promise, but no study has evaluated clinically relevant worsening of depressive symptoms.

Simonsson and colleagues identified all published psilocybin clinical trials on depression and conducted an individual participant data meta-analysis to assess the prevalence of clinically relevant worsening of depressive symptoms and baseline demographic characteristics associated with symptom worsening or treatment response.

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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

https://doi.org/10.1016/j.psychres.2023.115349

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Cite this paper (APA)

Simonsson, O., Carlbring, P., Carhart-Harris, R., Davis, A. K., Nutt, D. J., Griffiths, R. R., Erritzoe, D., & Goldberg, S. B. (2023). Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis. Psychiatry Research, In Press. Advance online publication. https://doi.org/10.1016/j.psychres.2023.115349

Study details

Compounds studied
Psilocybin

Topics studied
Depression

Study characteristics
Meta-Analysis

Participants
102 Humans

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