Real-world effectiveness and safety of xanomeline and trospium for treatment-resistant schizophrenia in a state hospital system

Objective Xanomeline and trospium (XT) is a novel medication for schizophrenia that was approved by the United States (U.S.) Food and Drug Administration (FDA) in September 2024. The purpose of this study is to evaluate the effectiveness and safety of using XT in the Texas state hospital setting. Methods Data were analyzed retrospectively from five hospitals within the Texas Health and Human Services Commission state hospital system. Adults aged ≥ 18 years administered XT between October 2024 and October 2025 were included. A chart extracted Clinical Global Impression (CGI) of Severity of Illness/Improvement was used to determine XT effectiveness. Patient demographics, clinical characteristics and documented adverse effects are reported. Results All patients (N = 20) had treatment-resistant schizophrenia and were classified as markedly or severely ill prior to XT initiation. All patients except one were prescribed ≥ 1 dopamine receptor blocking agents (DRBA)s while taking XT, with olanzapine (n=9; 45%) and clozapine (n=6; 30%) being most common. Fourteen patients (70%) discontinued XT during the study time frame due to intolerability (n=9; 45%) and/or lack of effectiveness (n=12; 60%). The average global improvement CGI score was 4 (no change). Gastrointestinal side-effects were most common, specifically, vomiting (n=9; 45%), dyspepsia (n=5; 25%), and sialorrhea (n=5; 25%). Conclusion In inpatients with TRS taking adjunct DRBAs (including anticholinergic DRBAs) XT use was commonly discontinued due to intolerability/ineffectiveness. Larger controlled trials are needed to further investigate XT’s effectiveness for treating TRS and determine how adjunct anticholinergic use impacts its safety/efficacy.