Inpatient Initiation of Cobenfy (Xanomeline-Trospium Chloride) During Acute Psychotic Decompensation in a Patient With Schizoaffective Disorder: A Case Report.

Xanomeline-trospium chloride (Cobenfy) is a novel muscarinic M1/M4 receptor agonist and a peripherally restricted antimuscarinic combination that represents a non-dopaminergic treatment approach for schizophrenia and related psychotic disorders. Although randomized clinical trials have demonstrated efficacy, published experience with inpatient initiation remains limited, particularly in patients undergoing transition from complex psychotropic polypharmacy. We describe the case of a 25-year-old nonbinary individual with schizoaffective disorder, depressive type, who was admitted for acute worsening of command auditory hallucinations and intermittent suicidal ideation in the setting of persistent psychotic symptoms despite multiple prior medication trials, including clozapine. During hospitalization, a structured medication wash was performed with sequential tapering and discontinuation of multiple psychotropic agents to reduce medication burden and clarify baseline symptomatology. Xanomeline-trospium was subsequently initiated and titrated to a therapeutic dose. Following initiation, the patient demonstrated improvement in the intensity and frequency of psychotic symptoms, resolution of active suicidal ideation by discharge, and good behavioral stability throughout hospitalization. The medication was well tolerated, with no extrapyramidal symptoms or other clinically significant adverse effects. This report highlights the feasibility and short-term tolerability of inpatient xanomeline-trospium initiation during a transition from complex psychotropic polypharmacy in a patient with acute psychotic decompensation.