Comparative efficacy and acceptability of psilocybin-ketamine and typical antidepressants for major depressive disorder management: a network meta-analysis

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.

Study at a glance

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.