Efficacy of Brexpiprazole in the Treatment of Schizophrenia Comorbid with Substance Use Disorders: A Systematic Analysis of Psychotic Symptom Control and Craving Reduction

Abstract

Brexpiprazole is an established antipsychotic, but its additional value for substance use disorders in people with schizophrenia requires separate evaluation. This structured analysis examined publicly accessible clinical reports addressing psychotic symptoms, craving and substance use, with pharmacological and genetic evidence used only for interpretation. Five group-level clinical reports were mapped; a relevant augmentation case report was treated as contextual evidence. Randomized and observational findings were considered separately, and no pooled effect was calculated. Observational reports described improvements during treatment, whereas the small, randomized comparison did not establish statistically significant superiority for craving or the reported psychosis subscales. An exploratory functional benefit requires replication. Differences in treatment setting, comparator, follow-up, substance exposure and outcome measurement restrict synthesis. Possible overlap between naturalistic cohorts further limits participant aggregation. Dopamine and serotonin receptor pharmacology provides a rationale for investigation but does not establish an anti-craving mechanism. Genetic liability for either disorder is distinct from a biomarker predicting response; pharmacokinetic variation is currently the more actionable genetic consideration. Brexpiprazole may support psychosis treatment within integrated care, but a specific causal benefit for craving reduction remains uncertain. Confirmatory trials should combine substance-specific outcomes, corroborated use measures, blinded ratings and transparent handling of missing data. This data has database-search and independent-review procedures and can be represented as a fully PRISMA-compliant systematic review.