Early outpatient clinical experience with xanomeline and trospium chloride for schizophrenia: a case series

Maxwell Zachary Price^1*Richard Louis Price²

• ¹Hackensack Meridian School of Medicine, Nutley, United States
• ²Yale University School of Medicine, New Haven, United States

The combination of xanomeline, a central/peripheral muscarinic agonist, and trospium chloride, a peripheral muscarinic antagonist, (X/T) was FDA approved in September 2024 for schizophrenia in adults. FDA trial subjects experiencing exacerbation or relapse of psychotic symptoms, who were neither treatment-resistant nor had taken clozapine, were tapered off previous antipsychotics, or were treatment-naive, prior to rapid X/T titration in the hospital as monotherapy. This case series addresses real-world clinical questions about how to use X/T when comorbidities with schizophrenia are the rule, polypharmacy is commonplace, and discontinuing antipsychotics prior to X/T initiation is often infeasible due to safety concerns in outpatient settings. Based upon our early experience treating 40 adult outpatients with schizophrenia and comorbidities using X/T to date, we present 3 representative cases to share clinical pearls we have uncovered through applying extant preclinical and clinical data. To maximize efficacy while ensuring tolerability, it is important to track cholinergic (e.g. nausea, vomiting, diarrhea) versus anticholinergic (e.g. gastroesophageal reflux, constipation, urinary retention) side effects, and to adjust X/T dose, titration, administration, and concomitant medications accordingly. X/T holds potential to improve cognitive deficits in comorbid autism or dementia warranting further study.