Brexpiprazole Effective for Schizophrenia in Teens

TOPLINE:

Brexpiprazole was associated with a greater reduction in schizophrenia symptoms over 6 weeks in adolescents compared with placebo, with a tolerable safety profile, in a new phase 3 trial.

METHODOLOGY:

• Researchers conducted a randomized, double-blind, parallel-arm, placebo-controlled, phase 3 trial with an active reference across 10 countries between 2017 and 2023.
• Overall, 316 patients with schizophrenia between age 13 and 17 years (mean age, 15.3 years; 53% girls) were randomly assigned to receive 2-4 mg/d oral brexpiprazole (n = 110), placebo (n = 104), or 10-20 mg/d aripiprazole (n = 102) over 6 weeks.
• The primary outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 6.
• Secondary outcomes included changes in PANSS Positive and Negative subscale, Clinical Global Impression (CGI)–Severity of Illness, CGI-Improvement, and Children’s Global Assessment Scale scores. Treatment-emergent adverse events (TEAEs) were also monitored during the trial.

TAKEAWAY:

• The brexpiprazole group showed significantly greater improvements in PANSS total score (least squares mean difference, −5.33; P = .014). The P values for all secondary outcome improvements vs placebo were “nominal,” the investigators reported.
• At least one TEAE was reported in 40%, 40%, and 52% of the brexpiprazole, placebo, and aripiprazole groups, respectively. Headache, nausea, and somnolence were the most common TEAEs in the brexpiprazole and placebo groups, whereas somnolence, fatigue, and akathisia were the most common in the aripiprazole group.
• Serious TEAEs were reported in 1%, 3%, and 1% of the brexpiprazole, placebo, and aripiprazole groups, respectively.
• There were no discontinuations in the brexpiprazole group because of TEAEs.

IN PRACTICE:

“The positive results of this trial, combined with previous extrapolation, pharmacokinetic, and long-term safety data, establish a body of evidence for brexpiprazole as a treatment option in adolescents with schizophrenia,” the investigators wrote.

The burden of side effects from antipsychotics is greater in children and adolescents with schizophrenia, wrote Maria Rogdaki, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, England, in an accompanying editorial. “In view of the unmet needs in the field of pediatric psychopharmacology in schizophrenia, this study makes an important contribution to the development of evidence-based pharmacological treatments in this age group,” Rogdaki wrote.

SOURCE:

The study was led by Caroline Ward, PhD, Otsuka Pharmaceutical Development & Commercialization, Princeton, New Jersey. The accompanying editorial and study were published online on April 7 in The Lancet Psychiatry.

LIMITATIONS:

The trial’s generalizability was limited by its exclusion criteria, the underrepresentation of racial minorities, and restrictions on concomitant medications. It was also not powered to assess secondary endpoints or to statistically compare results of brexpiprazole and aripiprazole. The 6-week duration prevented the evaluation of long-term treatment needs, and recruitment took about 6 years because of ethical, regulatory, and competitive challenges. The COVID-19 pandemic further affected the study, with differences in site distribution before and after its onset limiting the establishment of conclusions. Additionally, individuals with lived experience of schizophrenia were not involved in the research or reporting process.

DISCLOSURES:

The study was funded by Otsuka Pharmaceutical Development & Commercialization and H. Lundbeck. All of the investigators reported having ties with various sources, and many declared being employees of the funding companies. Full details are provided in the original article. The editorialist reported no having relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.