Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use

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https://www.psychiatrist.com/jcp/brexpiprazole-co-occurring-schizophrenia-substance-use-disorder-randomized-controlled-trial/?utm_source=Klaviyo&utm_medium=email&utm_campaign=news_wmr&klid=01HYSTTNXNB74YAYKT9XMYQCN0&_kx=va3uRF3O8-7Dg_zjrKMZJk0wdery-TOTVyZ3l8muM1g.VpkqxC

Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use Disorder: A Multisite, Randomized, Controlled Trial

October 13, 2025

Abstract
Objective: This proof-of-concept study examined the effects of brexpiprazole treatment on substance use, psychiatric symptoms, and quality of life in patients with co-occurring schizophrenia and substance use disorder.

Methods: In this 12-week study, patients diagnosed with schizophrenia and substance use disorder using DSM-5 criteria were randomly assigned to switch from their current antipsychotic medication to brexpiprazole (up to 4 mg/day) or remain on their current antipsychotic treatment (treatment as usual [TAU]). Substance use was assessed by the number of days of substance use and the dollars spent on substance in the past week, and substance craving was assessed using the Visual Analog Scale (VAS). Quality of life was assessed using the Heinrichs-Carpenter Quality of Life Scale (QOL). In addition, psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale-Severity of Illness.

Results: Thirty-nine patients were randomized (21 in the brexpiprazole group, 18 in the TAU group). Mixed models for repeated measures showed that, despite the lack of statistical significance, a consistent pattern of decrease in the brexpiprazole group was observed for the number of days of substance use and the dollars spent, as well as substance craving; the brexpiprazole group had a 15.5 points greater decrease in VAS (P=.157) and a $33.3 greater decrease in the dollars spent (P=.108) from baseline to week 12 compared with the TAU group. The brexpiprazole group did show a statistically significant 8.9 points greater increase in QOL compared with the TAU group (P =.020). Even though it was not statistically significant, the brexpiprazole group had a 2.4-point greater decrease in the PANSS General Psychopathology subscale score (P=.150) and a 1.9-point greater decrease in the PANSS Negative Symptom subscale score (P=.126) compared with the TAU group.

Conclusion: This study suggests that brexpiprazole might be beneficial in reducing substance craving and use in patients with schizophrenia and co-occurring substance use disorder; this potential benefit may help improve quality of life and overall psychiatric symptoms in a difficult-to-treat patient population.