LONGITUDINAL TRENDS IN ANTIPSYCHOTIC POLYTHERAPY AND ASSOCIATED OUTCOMES IN SCHIZOPHRENIA

Introduction

For > 70 years, schizophrenia management has relied on antipsychotic (AP) therapies that directly bind D2 dopamine receptors, largely switching or combining agents to control symptoms. However, safety and efficacy of combining APs are not well understood. This study described the demographic and clinical characteristics of adults with schizophrenia, evaluated AP monotherapy and polytherapy utilization patterns, and investigated the association between polytherapy and adverse events (AEs) and outcomes in real-world clinical practice.

Methods

Adults with schizophrenia initiating AP therapy from 01/01/2018-12/31/2024 were identified using the IQVIA PharMetrics® Plus database. The index date was the first AP claim after 01/01/2018, preceded by a 12-month AP-free baseline period. Monotherapy and polytherapy utilization patterns and associated risks of developing AEs of interest (hypertension, dyslipidemia, obesity, sleep-wake disorder, type 2 diabetes, major adverse cardiovascular events, extrapyramidal symptoms) were evaluated in the follow-up period. Polytherapy was defined as concurrent use of ≥2 APs for ≥90 days, allowing for a 32-day gap between prescriptions.

Results

6830 participants met study criteria (63.1% male; mean±SD age: 42.8±16.7 years). After the index date, proportions of participants with ≥1 polytherapy episode increased from 8.3% (year 1) to 20.0% (year 5); average±SD polytherapy duration increased from 229.1±107.5 days to 640.1±570.1 days. Polytherapy most often involved multiple oral second-generation APs (41.7%), oral + long-acting injectable (LAI) second-generation AP combinations (29.6%), and oral first- + second-generation AP combinations (18.8%). The most commonly prescribed monotherapies were oral second-generation APs (76.0%), short-acting injectable first-generation APs (21.5%), and LAI second-generation APs (21.4%). Use of other psychotropic medication also increased from year 1 to year 5 postindex (antidepressants: 45.0% to 63.1%; anxiolytics: 43.6% to 59.1%; mood stabilizers: 21.0% to 29.7%; anticholinergics: 36.3% to50.1%; and anticonvulsants: 13.3% to 21.9%). Proportions of participants with incident hypertension, dyslipidemia, obesity, sleep-wake disorders, and type 2 diabetes increased during follow-up. Risks of developing these conditions were similar regardless of exposure to monotherapy or polytherapy, except for sleep-wake cycle disorders. Among 793 participants with ≥1 polytherapy episode during follow-up, 53.7% had baseline conditions of interest. Of those without, 36.5% had polytherapy before an incident AE. Compared with those receiving monotherapy only, participants with ≥1 polytherapy episode had significantly higher all-cause and schizophreniarelated outpatient and total healthcare resource utilization (HCRU) and all-cause and schizophrenia-related outpatient, prescription, and total costs.

Conclusions

Rates of AP polytherapy use increased over time, including combinations of LAI and oral APs as well as multiple oral APs. Adults without underlying conditions of interest developed AP-related AEs during treatment, without significant differences in risk between monotherapy and polytherapy, except for sleep-wake disorders. Polytherapy was associated with higher all-cause and schizophrenia-related HCRU and costs. Increasing incidence and prolonged duration of polytherapy over the illness course underscore the unmet treatment needs of individuals with schizophrenia and the need to re-evaluate treatment approaches as new options emerge.