Robust Efficacy and Decreased Side Effects with New Muscarinic Agent for Treating Schizophrenia

CONFERENCE REPORTER

Chelsie Monroe, APN, PMHNP-BC, discussed at the Southern California Psychiatry Conference about new schizophrenia treatments which use the muscarinic pathway: “this has the efficacy that we’re looking for in a robust antipsychotic without the baggage of metabolic syndrome, tardive dyskinesia, motor movements…you have the efficacy without some of the downsides.” This new muscarinic action medication, xenomeline-trospium (Cobenfy), has the ability to change both positive, negative, and cognitive symptoms of schizophrenia.

Monroe expressed enthusiasm about this new type of treatment because it has a novel mechanism of action that has not been used previously in treating schizophrenia. By using this new cholinergic pathway, there is a new way to modulate dopamine in the brain. Monroe specified that new medications using this mechanism of action “don’t have the same baggage as our D2 antagonists” that often have detrimental side effects. She also reminded that clinicians should be thinking about a multitude of symptoms in their patients with schizophrenia and viewing the patient as a whole when prescribing medications for schizophrenia.

In looking to start patients on new cholinergic antipsychotics, Monroe noted clinicians must be mindful if the patient is already on traditional antipsychotics (like an anticholinergic), because a combination of these with a muscarinic agonist may lead to unwanted changes in the muscarinic system. New muscarinic agents are approved for use as monotherapy, but Monroe acknowledged that clinicians are constantly trying to find the best course of action or combination of treatments that best fit their patients with schizophrenia. Monroe explained that we have strong evidence for xenomeline-trospium as being effective because the effect sizes from studies are robust, even in comparison to other antipsychotics.

Chelsie Monroe 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. Bukhari SMR, Btool S, Abbas J,et al. Cobenfy (xanomeline-trospium): a breakthrough FDA-approved therapy redefining schizophrenia treatment. Ann Med Surg (Lond). 2025;87(6):3065-3067.