Efficacy and safety of brexpiprazole in patients with schizophrenia presenting with severe symptoms: Post-hoc analysis of short- and long-term studies

Abstract

Background: The treatment of patients with severe schizophrenia symptoms can be complicated and expensive.

Aims: The purpose of this study was to evaluate the short- and long-term effects of brexpiprazole in patients with schizophrenia presenting with severe symptoms.

Methods: Data were pooled from three six-week, randomized, double-blind, placebo-controlled studies and two 52-week, open-label extension studies. In the short-term studies, 1405 patients received placebo or brexpiprazole 2-4 mg/day; 412 brexpiprazole-treated patients rolled over into the long-term studies and received brexpiprazole 1-4 mg/day. More severe symptoms were defined as a Positive and Negative Syndrome Scale Total score >95 (median score at baseline). Outcomes included change in Positive and Negative Syndrome Scale Total and Personal and Social Performance scale scores.

Results: Brexpiprazole improved Positive and Negative Syndrome Scale Total score over 6 weeks among more severely ill patients, with a least squares mean difference versus placebo of -6.76 (95% confidence limits: -9.80, -3.72; p<0.0001; Cohen's d: 0.43). Brexpiprazole also improved Personal and Social Performance scale score over 6 weeks in more severely ill patients (least squares mean difference: 4.38; limits: 2.14, 6.62; p=0.0001; Cohen's d: 0.38). Improvement of functioning was greatest in the 'Self-care' domain, followed by 'Personal and social relationships'. Among less severely ill patients, brexpiprazole was superior to placebo on Positive and Negative Syndrome Scale Total and Personal and Social Performance scale at Week 6. Improvements were maintained over 58 weeks. No new safety or tolerability concerns were observed.

Conclusions: Brexpiprazole is an efficacious and well-tolerated treatment for schizophrenia in patients with more severe, and less severe, symptoms.

Keywords: Brexpiprazole; patient function; schizophrenia; severe symptoms; treatment outcome.

Figure 1.

Positive and Negative Syndrome Scale (PANSS) Total score change during (a) short-term and (b) long-term treatment with brexpiprazole, and (c) Personal and Social Performance scale (PSP) score change during long-term treatment, stratified by baseline illness severity (efficacy sample). Baseline PANSS Total score: (a) more severely ill placebo, 105.6; more severely ill brexpiprazole, 105.8; less severely ill placebo, 87.4; less severely ill brexpiprazole, 86.6; (b) more severely ill, 106.3; less severely ill, 86.0. Baseline PSP score: (c) more severely ill, 40.5; less severely ill, 48.6. LS: least squares; MMRM: mixed model for repeated measures; OL: open-label; SD: standard deviation; SE: standard error. *p<0.05, **p<0.01, ***p<0.001 versus placebo; MMRM (short-term); observed cases (long-term).