Impact of Long-Acting Injectable Versus Oral Antipsychotic Treatment on All-Cause Discontinuation Risk in People with Early Phase Schizophrenia and Comorbid Substance Use Disorder: A Secondary Analysis of the EULAST Randomized Trial.
Matin Mortazavi, Zahra Aminifarsani, Inge Winter-van Rossum, René S Kahn, W Wolfgang Fleischhacker, Michael Davidson, Mark Weiser, Dan Siskind, Stefan Leucht, Alkomiet Hasan, Elias Wagner
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Abstract
Background: Individuals with schizophrenia and comorbid substance use disorder (SUD) often experience poor treatment adherence, leading to worse clinical outcomes. However, high-quality evidence from randomized trials on the preferred mode of antipsychotic treatment in this population remains limited.
Aims: The aim was to examine whether long-acting injectable (LAI) antipsychotic treatment reduces the risk of all-cause discontinuation (ACD) compared with oral antipsychotics in individuals with early phase schizophrenia and comorbid SUD.
Methods: This study was a secondary analysis of the European Long-Acting Antipsychotics in Schizophrenia Trial (EULAST), a multisite, randomized, open-label trial conducted across multiple European healthcare settings. A total of 471 individuals with early phase schizophrenia were included in this secondary analysis, stratified by presence (n = 143) or absence (n = 328) of comorbid SUD. The observation period lasted 18 months. Participants were randomly assigned to second-generation LAI or oral second-generation antipsychotic treatment. The primary outcome was ACD, an indirect measure of treatment efficacy, defined as discontinuation of the initially assigned treatment for any reason. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models, adjusted for relevant covariates.
Results: Among 143 individuals with schizophrenia and SUD, LAI treatment was associated with a 36% lower risk of ACD compared with oral antipsychotics (adjusted HR = 0.641; 95% CI, 0.438-0.938; P = 0.022). Kaplan-Meier curves showed longer median time to ACD for LAI treatment (158 days) versus oral antipsychotics (97 days). By contrast, among the 328 individuals without SUD, LAI treatment did not significantly reduce ACD risk (P = 0.282). Crude HRs were also assessed, replicating the adjusted hazard findings.
Conclusions: LAI antipsychotics significantly delayed treatment discontinuation compared with oral antipsychotics in participants with early phase schizophrenia and comorbid SUD but not in those without SUD. While these findings provide robust evidence supporting the use of LAIs in people with schizophrenia and comorbid SUD, future studies are needed to more precisely quantify the potential clinical benefits and tolerability of LAIs in this high-risk population. EULAST was registered at ClinicalTrials.gov (NCT02146547).
期刊介绍：
CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes:
- Overviews of contentious or emerging issues.
- Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses.
- Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
- Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry.
- Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies.
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