Brexpiprazole for anxiety symptoms in schizophrenia: a pooled analysis of short- and long-term trials.

Objective: For people with schizophrenia and their caregivers, anxiety is among the top symptoms for which they would like an effective treatment. The aims of this analysis of clinical trial data were to characterize the efficacy, safety and tolerability of brexpiprazole on anxiety symptoms in adults with schizophrenia, and to investigate the relationships between anxiety symptoms, functioning, and patient life engagement.

Methods: Data were pooled for brexpiprazole 2-4 mg/day and placebo from three 6-week, randomized, double-blind trials of brexpiprazole in adult inpatients with schizophrenia (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380) and for brexpiprazole 1-4 mg/day from two 52-week, open-label extension trials (NCT01397786, NCT01810783). People with comorbid anxiety disorders were not enrolled. In this analysis, anxiety was measured by a single item (G2) of the Positive and Negative Syndrome Scale (PANSS), functioning was measured by the Personal and Social Performance scale, and patient life engagement was measured by a 14-item PANSS subset. Least squares mean changes from baseline were calculated using a mixed model for repeated measures. Anxiety response was defined using two definitions: (1) PANSS G2 improvement of ≥1 point (a clinically interpretable score change) from baseline to Week 6, and (2) PANSS G2 score of <3 points (anxiety symptoms reduced to 'minimal' or 'absent') at Week 6 for the subgroup who had anxiety at baseline (G2 score ≥3). This was an exploratory, hypothesis-generating analysis with no correction for multiple comparisons.

Results: Anxiety at baseline (G2 score ≥3) was present in 763/868 (87.9%) participants on brexpiprazole, and 449/517 (86.8%) on placebo. At Week 6, least squares mean change from baseline in G2 score favored brexpiprazole versus placebo: mean difference, -0.19; 95% confidence interval, -0.33 to -0.06; p = 0.005; Cohen's effect size, 0.19. Anxiety response for brexpiprazole and placebo, respectively, was shown in 547/863 (63.4%) and 291/515 (56.5%) participants (p = 0.012; response definition 1), and 283/541 (52.3%) and 135/303 (44.6%) participants (p = 0.036; response definition 2). Functioning and patient life engagement improved regardless of whether participants' anxiety improved. Long-term data suggested maintenance of treatment effects. Adverse events were consistent with prior analyses.

Conclusion: Exploratory analyses suggest that brexpiprazole may help in the management of anxiety symptoms, functioning, and patient life engagement - important outcomes for people with schizophrenia.