2026 ECNP Congress

PS03-3227

Real-world effectiveness of antipsychotic medications for relapse prevention in first-episode psychosis with substance use disorder

Antti Mustonen — S. Niemelä, M. Lähteenvuo, A. Denissoff, A. Tanskanen, E. Mittendorfer-Rutz, J. Tiihonen, H. Taipale · Tampere University, Faculty of Medicine and Health Technology, Seinäjoki, Finland

2026 ECNP Congress

Background

Comorbid psychotic and substance use disorders are associated with an increased disease burden, including more severe symptomatology and more frequent relapse. Research suggests that antipsychotic medication is effective in preventing relapses in individuals with comorbid schizophrenia and substance use disorder. Limited real‑world evidence indicates that antipsychotic medications may be beneficial in first‑episode psychosis (FEP) with comorbid cannabis use disorder; however, the extent to which these benefits generalize across all substance use disorders remains unknown.

Aims

Our aim was to study the real-world effectiveness of antipsychotic medications in relapse prevention in individuals with FEP&SUD.

Methods

We used data from a nationwide linkage of several administrative and health care registers in Sweden to identify all individuals with Swedish residency who were diagnosed with FEP (ICD‑10 F2x) and comorbid substance use disorder (SUD; ICD‑10 F1x). Antipsychotic exposure was modelled as a time‑dependent variable using the validated PRE2DUP method. Using within‑individual models in stratified Cox regression analyses, we examined the risk hospitalization for any psychotic episode, defined as schizophrenia‑spectrum disorders (F20–F29) or substance‑induced psychosis (F1x.5), during the use of different oral or long-acting injectable (LAI) antipsychotics compared with non-use. Individuals were followed from the cohort entry (index date for the FEP&SUD diagnoses) until emigration, death, or the end of data linkage (December 2023), whichever occurred first.

Results

We identified 11,292 individuals (75.52% men) aged 16-64 years with FEP&SUD between 2006 and 2021. The mean age at first diagnosis was 32.74 years (SD 11.44). During the follow-up, 5089 individuals (45.1% of the sample) were hospitalised due to psychosis at least once. Any antipsychotic use was associated with a decreased risk of hospitalisation due to psychosis (adjusted hazard ratio (aHR) 0.74; 95% CI 0.70–0.76). Use of oral antipsychotic monotherapies (aHR 0.80; 0.75–0.84) and as well as LAIs (aHR 0.58; 0.53–0.64) was associated with a reduced risk of hospitalisation due to psychosis compared to non-use of antipsychotics, but LAIs were associated with a smaller risk than oral monotherapies (aHR 0.73; 0.66–0.80). Specific antipsychotics associated with decreased risk included clozapine (aHR 0.53; 0.44–0.64), aripiprazole LAI (aHR 0.55; 0.45–0.68), paliperidone LAI (aHR 0.57; 0.47–0.69), risperidone LAI (aHR 0.59; 0.45–0.78), perphenazine LAI (aHR 0.61; 0.48–0.77), olanzapine LAI (aHR 0.69; 0.53–0.89), haloperidol LAI (aHR 0.73; 0.56–0.94), antipsychotic polytherapy (aHR 0.78; 0.73–0.83), oral olanzapine (aHR 0.82; 0.76–0.88) and oral aripiprazole (aHR 0.86; 0.75–0.98), while quetiapine and risperidone did not show statistically significantly decreased risk. When studied by dose categories, any LAI (<1.6 DDDs/day), clozapine (<1.6 DDDs/day), olanzapine (all dose ranges), aripiprazole (<1.1 DDDs/day) were effective, while quetiapine and risperidone showed no significant benefit.

Conclusions

Notably, clozapine and LAIs were associated with a reduced risk of hospitalisation due to psychosis among patients with FEP&SUD. These findings highlight the importance of considering wider use of LAIs for relapse prevention to improve outcomes in this clinically complex population.

References

No references.