Efficacy and Safety of Brexpiprazole in Patients With Schizophrenia Presenting With Severe Psychotic Symptoms During an Acute Exacerbation

Background: Schizophrenia is a chronic, disabling and progressive disease, with heterogenous symptoms and disease course between individuals. Severity of symptoms has been shown to be a significant predictor of poor treatment outcomes.

Methods: We performed a post hoc analysis of short-term studies (Vector [NCT01396421], Beacon [NCT01393613], and Lighthouse [NCT01810380]) to evaluate the efficacy of brexpiprazole in the subgroup of patients with severe psychotic symptoms, defined as those patients with baseline Positive and Negative Syndrome Scale (PANSS) Total score above the median score of 95. Change from baseline to Week 6 in PANSS Total score, PANSS Positive and Negative subscale scores, PANSS Excited Component (PEC) score, Clinical Global Impressions Improvement and Severity (CGI-I, CGI-S) scores, Marder factor scores, and overall response rate were assessed.

Results: A total of 681 patients had severe schizophrenia at baseline (brexpiprazole 2–4 mg, n=427; placebo, n=254). Statistically significant and clinically meaningful improvements in PANSS Total score compared to placebo were demonstrated with brexpiprazole 2–4 mg, with a placebo-adjusted difference of 6.76 (p<0.0001). Significant and clinically meaningful advantages of brexpiprazole were also demonstrated for the PANSS subscales, PEC score, CGI-I, CGI-S, Marder factor scores. Overall response rates at Week 6 were significantly greater for brexpiprazole 2–4 mg (46.9%; p<0.0001) versus placebo (27.3%). Adverse events with incidence ≥5% were headache, agitation, insomnia, and schizophrenia.

Conclusions: Brexpiprazole demonstrated robust efficacy in the treatment of patients experiencing severe psychotic symptoms. This analysis showed that brexpiprazole was safe and well tolerated in patients with severe psychotic symptoms.