Long-Acting Injectable Antipsychotics in Schizophrenia and Comorbid Substance Use Disorder: A Systematic Review of the Literature

Abstract

Highlights What are the main findings? Nine studies involving 2062 patients with schizophrenia and comorbid substance use disorder (SUD) were included, with follow-up periods ranging from 6 months to 3 years. Several studies reported favorable clinical outcomes with long-acting injectable (LAI) antipsychotics, but the evidence was mixed and did not consistently demonstrate superiority over oral antipsychotics. What are the implications of the main findings? LAI antipsychotics may be a valuable treatment option for patients with schizophrenia and comorbid SUD, particularly where adherence to oral medication is a concern. The heterogeneity of the available evidence highlights the need for more high-quality, standardized research to better establish the efficacy, effectiveness, and safety of LAIs in this patient population. Abstract Background/Objectives: The aim of this systematic review is to assess the efficacy, effectiveness, and safety of LAI antipsychotics in patients with schizophrenia and comorbid SUD, providing useful information for clinical decision making and guiding future research in the management of this complex patient population. Methods: The search was conducted on 1 July 2026 and produced 87 results in total; after the screening process, 78 articles were excluded based on the predefined eligibility criteria. The full texts of the remaining 9 studies were retrieved and thoroughly evaluated for inclusion in the qualitative synthesis. Results: The 9 articles that met the criteria for inclusion included 2062 patients in total with follow-up periods varying between 6 months and 3 years. Several studies reported favorable clinical outcomes associated with LAIs; however, not all studies demonstrated clear superiority of LAIs over oral antipsychotics. Conclusions: The present review suggests that LAIs may represent a valuable therapeutic strategy for patients with schizophrenia and comorbid SUD, although the available evidence remains heterogeneous in terms of study design, patient populations, and outcome measures.