Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta‐analysis

• Published in: Neuropsychopharmacology reports 2024-03, Vol.44 (1), p.165-175
• Main Authors: Kishi, Taro, Sakuma, Kenji, Saito, Takeo, Nakagawa, Atsuo, Kato, Masaki, Iwata, Nakao
• Format: Article
• Language: English
• Subjects: Antidepressants; Antipsychotics; aripiprazole; Bias; brexpiprazole; Cytochrome; Dopamine; Drug dosages; Japanese major depressive disorder; Mental depression; Meta-analysis; Metabolism; Minority & ethnic groups; network meta‐analysis; Original; Patients; Psychotropic drugs; Substance abuse treatment; Systematic review
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12414

Aim This systematic review and frequentist network meta‐analysis used random‐effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants. Methods Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non‐response rate; the non‐remission rate; all‐cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain. Results A literature search identified three double‐blind, randomized, placebo‐controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible‐dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day. Conclusions Overall BRE showed similar utility to ARI and a good risk–benefit balance. This network meta‐analysis is conducted to determine whether there are differences in the efficacy, acceptability, tolerability and safety profiles of brexpiprazole and aripiprazole for Japanese with major depressive disorder. Overall, brexpiprazole showed similar utility to aripiprazole and a good risk‐benefit balance. The risk of akathisia in brexpiprazole 2 mg/day was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.