Efficacy and safety of 2-4 mg brexpiprazole in the management of schizophrenia: A systematic review and meta-analysis.

Abstract

Brexpiprazole 2-4 mg daily is a novel dopamine D2 partial agonist approved for schizophrenia and improves effectiveness and tolerance by balancing D2, 5-HT1A, and 5-HT2A effects. This review assesses current evidence on its efficacy and safety within this dose range. PubMed, ScienceDirect, and The Cochrane Library were searched for trials published between 2011 and 2025 using specific keywords. Eligibility criteria included schizophrenia patients diagnosed using DSM-IV, DSM-IV-TR, DSM-5, or ICD-10, with intervention being 2-4 mg of brexpiprazole. Positive and Negative Syndrome Scale (PANSS) score and Clinical Global Impression - Severity scale (CGI-S) were the primary efficacy endpoints, and treatment-related adverse events were used to assess efficacy. Subgroup analysis was planned between the two dosage groups. The quality of randomized controlled trials (RCTs) was evaluated using the ROB2 tool, and the protocol registration was completed in PROSPERO. Among 464 retrieved articles, five trials with 2182 participants were found to be eligible. Brexpiprazole significantly improved total PANSS scores (mean difference [MD] -5.76; 95% confidence interval [CI] -7.69 to -3.83; p < 0.00001), positive subscale scores, negative subscale scores, and CGI-S scores (MD -1.35; 95% CI -1.87 to -0.84; p < 0.00001). The treatment-emergent adverse events were similar to placebo, and the risk of discontinuation was less with brexpiprazole (risk ratio 0.58; 95% CI 0.430.77; p = 0.0002). The most usual extrapyramidal symptom was akathisia. Brexpiprazole 2-4 mg showed significant improvements in PANSS and CGI-S scores, with a lower risk of treatment discontinuation. These findings support its efficacy and tolerability in managing schizophrenia.