REAL-WORLD USE OF XANOMELINE AND TROSPIUM CHLORIDE IN SCHIZOPHRENIA: PATIENT CHARACTERISTICS, TREATMENT PATTERNS, AND OUTCOMES

Introduction

Schizophrenia imposes a substantial burden on patients and health systems in the United States. For decades, pharmacologic treatment of schizophrenia has relied on D2 dopamine receptor antagonists, which can have substantial side effects, such as cardiometabolic conditions and extrapyramidal or other movement disorders. KarXT (xanomeline and trospium chloride) was approved by the US Food and Drug Administration in September 2024 for the treatment of schizophrenia and represents a new treatment option that exerts effects through M1 and M4 muscarinic receptor circuits rather than D2 dopamine receptors. This study aims to describe real-world clinical characteristics, treatment patterns, and outcomes of adults initiating KarXT treatment for schizophrenia.

Methods

This retrospective observational study analyzed administrative claims from the Komodo Research Database (January 1, 2016-April 30, 2025), a large, nationally representative database with approximately 300 million patient journeys and healthcare encounters from more than 150 payers across Medicaid, commercial, and Medicare insurers. Adults with schizophrenia who initiated KarXT between September 2024 and March 2025 were included. Demographics and clinical characteristics were assessed over the 12 months prior to KarXT initiation (baseline). Adherence (proportion of days covered [PDC]) and persistence (time to discontinuation with a 45-day allowable gap) were evaluated post KarXT initiation (follow-up). Rates of antipsychotic (AP) and other psychotropic medication use were compared before and after KarXT initiation.

Results

A total of 1443 adults with schizophrenia who initiated KarXT were included (mean age=42.2 years); most were insured by Medicare and Medicaid. Prior to KarXT initiation, the study cohort had high utilization of APs (99%) and other psychotropic medications, including antidepressants (74%), anticholinergics (56%), anxiolytics (51%), and mood stabilizers (48%). The prevalence of cardiometabolic conditions, mental health-related comorbidities, and other AP-associated disorders was also high (≤49%). During the follow-up, adherence and persistence to KarXT were relatively high, with 72% having a PDC ≥80% and approximately 81% persisting on KarXT through month 4. AP use decreased after KarXT initiation (rate ratio [RR]=0.74 for orals, P < 0.001; 0.78 for long-acting injectables, P < 0.001), as did use of mood stabilizers (RR=0.87, P < 0.001) and anticholinergics (RR=0.84, P < 0.001). A decreasing trend was observed for antidepressant use (RR=0.96, P=0.053).

Conclusions

Adults with schizophrenia who initiated KarXT in the first 6 months of availability exhibited high treatment and comorbidity burdens. During the brief follow-up, adherence and persistence to KarXT were relatively high. Following KarXT initiation, use of APs, mood stabilizers, and anticholinergics reduced significantly, suggesting a potential shift toward a simplified treatment regimen for managing schizophrenia.