• Zahinoor Ismail, Stine Rasmussen Meehan, Anja Farovik, Shivani Kapadia, Anton M Palma, Zhen Zhang, and Roger S McIntyre.
• Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
• Curr Med Res Opin. 2025 Jan 3: 191-9.

ObjectivePatients with schizophrenia value improved life engagement, a term that describes positive health aspects across emotional, physical, social, and cognitive domains. This post hoc analysis of clinical trial data aimed to investigate the effect of brexpiprazole on patient life engagement in schizophrenia over the short and long term.MethodsData were pooled from three 6-week, randomized, double-blind, placebo-controlled clinical trials (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380; N = 1385) and two 52-week, open-label extension studies (NCT01397786, NCT01810783; N = 408) of brexpiprazole in adults with schizophrenia. Patient life engagement was measured using a subset of 14 Positive and Negative Syndrome Scale items (score range: 14 [best] to 98 [worst]) that has previously demonstrated content validity. Mean score changes and response rates (based on minimal clinically important difference estimates of ≥5 and ≥10 points) were calculated.ResultsGreater improvement in patient life engagement from baseline to Week 6 was observed for brexpiprazole 2-4 mg/day (least squares mean [standard error] change: -8.3 [0.3]; n = 868) versus placebo (-5.7 [0.4]; n = 517), with a least squares mean difference of -2.58 (95% confidence interval: -3.57 to -1.58; p < 0.001; Cohen's d effect size: 0.28). These improvements were maintained over 58 weeks on brexpiprazole 1-4 mg/day (n = 399). At Week 6, response rates among patients treated with brexpiprazole versus placebo were 71.6% versus 58.0% (≥5-point improvement; p < 0.001) and 43.5% versus 32.8% (≥10-point improvement; p < 0.001). At Week 58 (n = 179), response rates among patients treated with brexpiprazole were 90.5% (≥5-point improvement) and 78.2% (≥10-point improvement).ConclusionBeyond its efficacy on psychotic symptoms, brexpiprazole has the potential to improve patient life engagement - an important patient-centered outcome in schizophrenia.

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