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

Introduction

Depression is a leading cause of global disability and current treatments do not reliably help all patients; some people fail to respond and others experience symptom worsening. Psilocybin-assisted therapy has produced reductions in depressive symptoms in several clinical trials, but prior work had not quantified clinically relevant worsening of depressive symptoms within psilocybin trials, nor had it thoroughly examined whether baseline demographic characteristics predict either symptom worsening or treatment response. Simonsson and colleagues set out to address this gap by performing an individual participant data (IPD) meta-analysis of published clinical trials of psilocybin for depression. The study aimed to (1) estimate the prevalence of clinically relevant worsening of depressive symptoms after psilocybin-assisted therapy and (2) examine whether baseline demographic variables were associated with symptom worsening or with treatment response. The authors hypothesised that rates of clinically relevant worsening would be lower in psilocybin conditions than in control conditions for trials that included controls, and they did not specify a priori hypotheses about demographic predictors.