SAN ANTONIO, TX—Brexpiprazole was efficacious in the maintenance treatment of patients with acute schizophrenia who met stability criteria, improving and maintaining psychosocial and occupational functioning over 52 weeks, according to findings from a randomized, double-blind, placebo-controlled efficacy, safety, and tolerability study presented at the U.S. Psychiatric & Mental Health Congress.

“While some akathisia was observed in the stabilization phase, brexpiprazole was overall reasonably tolerated,” reported lead study author Catherine Weiss, PhD, of Otsuka Pharmaceutical Development & Commercialization, Inc., in Princeton, NJ, and coauthors. 

However, the analysis was based on a small number of patients, “mostly due to early termination of the study following the interim analysis,” they cautioned.

Psychosocial deficits are a “core feature” of schizophrenia and social functioning outcomes are an important measure of treatment success. Brexpiprazole is a partial agonist of the 5-HT1A and dopamine D2 receptors, and an antagonist of 5-HT2A and the noradrenaline alpha1B/2C receptors. 

Patients included in this 52-week study were 18–65 year-old outpatients who had schizophrenia for three or more years and a history of relapse or symptom exacerbation when not on antipsychotic medication. Patients with current suicidal behavior or violent or aggressive behavior were excluded from the study.

Ninety-six patients were randomly assigned to receive brexpiprazole (1-4mg) and 104 patients received placebo.

The study involved a screening phase and 3 treatment phases, followed by a safety period, the authors reported; treatment phases were phase A (conversion); B (stabilization); and C (double-blind maintenance). The primary study endpoint was time from randomization to psychotic symptoms exacerbation or impending relapse in treatment phase C. (Psychotic symptoms/impending relapse criteria included a CGI score of ≥5 and an increase on PANSS scores for conceptual disorganization, suspiciousness, hallucinatory behavior, or unusual thought content; hospitalization due to worsening psychotic symptoms; suicidal behavior; or violent or aggressive behavior resulting in injury or property damage.)

Time to exacerbation of psychotic symptoms/impending relapse was significantly longer among patients in the brexpiprazole study group (hazard ratio [HR]: 0.292; P<0.0001), the authors reported. 

“The treatment difference at Weeks 24 and 52 represented a greater increase in social functioning for subjects in the brexpiprazole group compared with the placebo group” (LOCF, ANCOVA: Week 24: 3.79; P=0.0285 and Week 52: 4.75; P=0.0071), they reported.

Treatment-emergent adverse events (TEAEs) occurring in 5% or more of patients in treatment phase C included headache (6.2% in brexpiprazole group vs. 9.6% in placebo group), insomnia (5.2% vs 7.7%), and nasopharyngitis (3.1% vs. 6.7%).