Effect of Brexpiprazole on Agitation and Hostility in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies.

ABSTRACT

BACKGROUND: Managing agitation and hostility represents a significant treatment challenge in schizophrenia. The aim of this analysis was to evaluate the short- and long-term efficacy of brexpiprazole for reducing agitation and hostility in schizophrenia. METHODS: This was a post hoc analysis of data from two 6-week, randomized, double-blind, placebo-controlled studies (ClinicalTrials.gov identifiers, NCT01396421 and NCT01393613) and a 52-week, open-label, extension study (NCT01397786). In the short-term studies, 1094 patients received placebo, 2 mg/d of brexpiprazole, or 4 mg/d of brexpiprazole; 346 brexpiprazole-treated patients rolled over into the long-term study and received 1 to 4 mg/d of brexpiprazole. Agitation was assessed using the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC), and hostility was assessed using the PANSS hostility item (P7). RESULTS: Brexpiprazole improved PANSS-EC score over 6 weeks, with least squares mean differences versus placebo of -0.69 (95% confidence limits, -1.28, -0.11) for 2 mg/d (P = 0.020) and -1.11 (-1.70, -0.53) for 4 mg/d (P = 0.0002). In the subgroup with hostility at baseline (P7 score ≥3; 50.8% of the randomized sample), least squares mean differences versus placebo at week 6 on the PANSS-EC were -0.63 (-1.54, 0.28) for 2 mg/d (P = 0.18) and -1.03 (-1.92, -0.14) for 4 mg/d (P = 0.024), and on P7 (adjusted for positive symptoms) were -0.27 (-0.53, -0.01) for 2 mg/d (P = 0.038) and -0.34 (-0.59, -0.09) for 4 mg/d (P = 0.0080). The improvements were maintained over 58 weeks. Adverse events were generally comparable between treatment groups over 6 weeks; the incidence of akathisia among patients with hostility was 5.9% with placebo, 5.2% with 2 mg/d, and 8.6% with 4 mg/d. CONCLUSIONS: Brexpiprazole has the potential to be an efficacious and well-tolerated treatment for agitation and hostility among patients with schizophrenia.