Comparative Efficacy of Dopamine Partial Agonists by Doses for Treatment-Resistant Depression: A Systematic Review and Dose-Response Model-Based Network Meta-analysis.

ABSTRACT

BACKGROUND: The augmentative antidepressant effects of dopamine partial agonists (aripiprazole, brexpiprazole, and cariprazine) for treatment-resistant depression have been compared in a previous network meta-analysis. However, the comparative efficacy of the dose-responses of these drugs remains unclear. Therefore, we aimed to estimate the dose-response relationships and compare the effects of each dopamine partial agonist doses. METHODS: We conducted a systematic review of the Cochrane Library, PubMed, CINHAL, and ClinicalTrials.gov databases until January 1, 2023. Double-blind, randomized, placebo-controlled trials evaluating aripiprazole, brexpiprazole, and cariprazine for treatment-resistant depression were included. A random-effect dose-response model-based network meta-analysis was conducted. This study was registered in PROSPERO (CRD42023393035). RESULTS: The maximum effective doses were 5.5 mg for aripiprazole, 1.6 mg for brexpiprazole, and 1.5 mg for cariprazine, respectively. Although all doses of the 3 drugs were significantly more effective than placebo, aripiprazole ranging from 5.5 to 12.5 mg was significantly more effective than brexpiprazole 0.5 mg and cariprazine ranging from 0.5 to 1 mg. Moreover, aripiprazole ranging from 7.5 to 12.5 mg was significantly more effective than all doses of cariprazine. In addition, brexpiprazole ranging from 1 to 3 mg was significantly more effective than cariprazine 0.5 mg and brexpiprazole ranging from 1.6 to 2.5 mg was significantly superior to cariprazine 1 mg. There were no doses at which brexpiprazole overcame aripiprazole, and cariprazine overcame aripiprazole or brexpiprazole. CONCLUSIONS: Aripiprazole, brexpiprazole, and cariprazine may be effective in treatment-resistant depression in that order, with the maximum effective doses at 5.5 mg, 1.6 mg, and 1.5 mg, respectively.