Clinician Tips in Prescribing New Xanomeline-Trospium for Schizophrenia

CONFERENCE REPORTER

Clinicians may tend to want to try out a new medication like xenomeline-trospium (X-T) as it becomes available, but Chelsie Monroe, NP cautioned this approach without careful consideration.¹ She pointed out that approximately 30% of patients with schizophrenia may be resistant to treatment; however, this resistance isn't always tied to dopaminergic issues, and other factors like glutamate levels may play a role.

For example, if a patient is already on clozapine, Monroe did not recommend discontinuing this medication in order to start a muscarinic agent like xenomaline-trospium. Patients who are on clozapine tend to be more easily destabilized, so switching them to a new medication could potentially worsen their condition. When considering the addition of X-T to a patient's regimen, particularly if they are already on clozapine, Monroe emphasized the need for caution and thoughtful evaluation. Adding a muscarinic agent medication like X-T, in combination with an anticholinergic like clozapine, could lead to an increase in cholinergic side effects.²

Monroe also addressed concerns that patients and providers might have about prescribing a new medication like X-T, which works differently from traditional antipsychotics. She reminded that the treatment of schizophrenia has always involved managing side effects that must be monitored throughout the patient's lifetime, but now the mechanisms behind X-T lead to fewer long term side effect concerns. Although patients may experience cholinergic side effects during the first few weeks to a month of taking X-T, these effects are often distinct from those associated with traditional antipsychotics.

Monroe encouraged clinicians to remain hopeful and excited about the new treatment option. She advised to reassure patients by emphasizing that X-T represents a "whole new mechanism of action." While some side effects may occur early on, Monroe said that if patients can persevere through the initial weeks, they may ultimately experience the therapeutic benefits of X-T without the drawbacks commonly seen with older antipsychotics.

Chelsie Monroe, NP, PMHNP-BC is a psychiatric nurse practitioner of over 10 years and founder of Balanced Mental Wellness.

References

1. Monroe, C. Cholinergic pathways in the pathophysiology of schizophrenia. Conference Proceedings of the Southern California Psychiatry Conference. July 2025;11-12. Huntington Beach, CA.

2. Terry AV Jr. Role of the central cholinergic system in the therapeutics of schizophrenia. Curr Neuropharmacol. 2008;6(3):286-292.