Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: a systematic review and individual participant data meta-analysis
Carhart-Harris, R. L., Davis, A. K., Erritzoe, D., Goldberg, S. B., Griffiths, R. R., Nutt, D. J., Simonsson, O.
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
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.