Real-World Implementation of Xanomeline-Trospium in Schizophrenia

Xanomeline-trospium (XT) is the first muscarinic-based therapy approved for schizophrenia. It combines M1 and M4 receptor agonism with peripheral antagonism to limit cholinergic side effects. By modulating circuits upstream of dopamine release, XT offers a mechanism that differs from traditional antipsychotics and may address positive, negative, and cognitive symptoms. In July 2025, a consensus panel of clinicians with expertise in treating schizophrenia and real-world experience using XT convened to discuss practical strategies for its use across treatment settings. The panel concluded that XT should be considered early in the course of illness, particularly in first-episode psychosis, because it may alter long-term outcomes while reducing reliance on high-dose dopamine antagonists. Outpatient strategies emphasize individualized titration and proactive management of gastrointestinal side effects to support adherence. Inpatient use allows for more rapid titration and has shown rapid benefits in both positive and negative symptoms, facilitating earlier stabilization and discharge. Cross-titration experience suggests that XT can be dose-sparing when combined with dopamine blockers, reducing the burden of metabolic and motor side effects. These real-world insights highlight XT as a versatile treatment option that expands the therapeutic possibilities for schizophrenia.