Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs.

A network meta-analysis of 72 randomized controlled trials with 12,105 participants found that electroconvulsive therapy (ECT), ketamine, esketamine, and psilocybin are superior first-line treatments for treatment-resistant depression (TRD) due to their optimal balance of effectiveness and tolerability. Brexpiprazole and quetiapine showed no significant efficacy over placebo in response rates. Esketamine and psilocybin exhibited lower tolerability. The findings advocate for ECT, ketamine, esketamine, and psilocybin as preferred treatments, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes.

Study at a glance

Abstract

Treatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies. A network meta-analysis following PRISMA guidelines examined the efficacy and safety of TRD treatments, analyzing 72 randomized controlled trials from eight databases, assessing response and remission rates, tolerability, and safety through the Cochrane Risk of Bias Tool and CINeMA framework. Including 12,105 participants, the analysis highlighted ECT, Ketamine, Esketamine, and Psilocybin as superior first-line treatments due to their optimal balance between effectiveness and tolerability. Brexpiprazole and Quetiapine showed no significant efficacy over placebo in response rates, while Esketamine and Psilocybin exhibited lower tolerability. The results advocate for ECT, Ketamine, Esketamine, and Psilocybin as preferred treatments for TRD, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes. This study underscores the importance of considering both efficacy and safety in selecting augmentation strategies for TRD.