Brexpiprazole, a serotonin-dopamine activity modulator already approved for adult schizophrenia, has now demonstrated efficacy and safety in adolescents in the first placebo-controlled trial of its kind. Published in The Lancet Psychiatry, this multi-country phase 3 study randomized 316 adolescents aged 13–17 years with schizophrenia to 6 weeks of treatment with brexpiprazole (2-4 mg/day), placebo, or aripiprazole (10-20 mg/day). The primary outcome was change in Positive and Negative Syndrome Scale (PANSS) total score.

Brexpiprazole showed significantly greater improvement than placebo at week 6 of treatment, with a least squares mean reduction in PANSS score of –22.8 versus –17.4 for placebo (difference –5.33; p=0.014), and performed similarly to aripiprazole (–24.0). Secondary endpoints, including response rate and PANSS positive symptoms, also favored brexpiprazole. Importantly, the incidence of treatment-emergent adverse events (TEAEs) was comparable to placebo (40% in both groups). The most common TEAEs with brexpiprazole were headache and nausea (6% each). Activating and sedating effects such as akathisia and somnolence were less frequent with brexpiprazole than with aripiprazole. No patients discontinued brexpiprazole due to TEAEs.

These findings suggest that brexpiprazole may represent a valuable addition to the pharmacologic toolkit for early-onset schizophrenia, offering a balance of efficacy and tolerability consistent with adult data. The results support the use of brexpiprazole in the adolescent population and may guide clinicians seeking safer, effective serotonin dopamine antagonists/partial agonist (SDA-PA) options for youth.

Reference:

Ward C et al. Lancet Psychiatry. 2025;12(5):345-354. Abstract