Control Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression
JAMA Network Open July 30, 2025 Fredrik Hieronymus, Evana López, Helena Werin Sjögren et al. 21 citations
In clinical trials for depression, patients given a placebo or control treatment in psilocybin trials showed significantly less improvement in depression ratings than those given control treatments in trials of SSRIs or esketamine. The meta-analysis of 17 trials found that control treatment response rates in SSRI trials were 14 percentage points higher than in psilocybin trials, and in esketamine trials were 23 percentage points higher. Dropout rates were similar for psilocybin and esketamine (5-12% active, 8-11% control) but much lower than for SSRIs (32% active, 35% control). These results suggest that psilocybin's antidepressant efficacy may be overestimated compared to SSRIs and esketamine.