Comparative efficacy and acceptability of psilocybin-ketamine and typical antidepressants for major depressive disorder management: a network meta-analysis
DELOS Desarrollo Local Sostenible December 11, 2025 Pedro Rodrigues, Weliton Rodrigues Dos Santos Júnior, Ivan de Sousa Araújo et al.
A systematic review and network meta-analysis of 149 randomized controlled trials compared psilocybin, ketamine, and several common antidepressants (escitalopram, bupropion, paroxetine, fluoxetine, sertraline, venlafaxine) against placebo for major depressive disorder. All antidepressants were more effective than placebo, but psilocybin and ketamine achieved the lowest depressive symptom scores and reduced suicidal ideation. For acceptability (measured by dropout rates), placebo outperformed all drugs; however, among the medications, psilocybin had the highest combined ranking for efficacy and acceptability, followed closely by ketamine. The authors suggest these two agents may aid physicians in therapeutic decision-making, including for treatment-refractory depression.