Comparative efficacy and acceptability of psilocybin-ketamine and typical antidepressants for major depressive disorder management: a network meta-analysis
Pedro Rodrigues, Weliton Rodrigues Dos Santos Júnior, Ivan de Sousa Araújo, Leonardo Maia Leony, Fernando Gomes, Thales Moreira de Lima, Lícia Maria Oliveira Moreira, Rc Santana, Márcia Ribeiro Valentão Pitrez Santos, R. Silva
DELOS Desarrollo Local Sostenible December 11, 2025 DOI: 10.55905/rdelosv18.n75-120 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with network meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 149 |
| Population | Adults with major depressive disorder in randomized controlled trials |
| Interventions | Psilocybin Ketamine Escitalopram Bupropion Paroxetine Fluoxetine Sertraline Venlafaxine |
| Topics | Depression Ketamine Psilocybin Esketamine |
| Keywords | Psychological intervention Suicidal ideation Placebo Randomized controlled trial Clinical psychology Meta-analysis Depression economics Clinical trial |
| Key findings | Psilocybin and ketamine showed superior efficacy and acceptability compared to other antidepressants and placebo in treating major depressive disorder. |
Abstract
Objective: To compare acceptability and effectiveness of psilocybin, ketamine and commonly prescribed antidepressants in the management of Major Depressive Disorder (MDD).
Methods: This is a systematic review with network meta-analysis. The survey was conducted between January and June 2023, employing MEDLINE, PsyINFO, Embase, Web of Science and ClinicalTrials.gov databases. Randomized controlled clinical trials involving escitalopram, bupropion, paroxetine, fluoxetine, sertraline, venlafaxine, ketamine or psilocybin in MDD were included. We analyzed effectiveness and acceptability of medications through depressive symptom scores and proportion of patients who dropped out, respectively.
Results: 5845 documents were identified, of which 149 were reviewed. In terms of efficacy, all antidepressants were more effective than placebo, with psilocybin and ketamine achieving a lower depressive symptom score and suicide ideation . Regarding acceptability, the placebo obtained significantly better results than evaluated drugs. Psilocybin had the highest surface under the cumulative ranking curve (SUCRA) score among the interventions with 100 and 86.96 for efficacy and acceptability followed to ketamine with 86.83 and 84.56, respectively.
Conclusions: Psilocybin and ketamine have been shown to be superior to all other interventions with regard to efficacy and acceptability, including the treatment-refractory MDD. Thus, the results seem to show in this study that the psilocybin e ketamine can serve for better decision-making by physicians in the therapeutic management of MDD.