Positive response to adjunctive KarXT (xanomeline/trospium) in treatment-resistant Schizophrenia: A case report

KarXT (xanomeline-trospium) is a novel, FDA-approved antipsychotic that targets muscarinic receptors rather than dopamine for use in patients with schizophrenia. Initial studies aimed at the approval of the drug showed a decrease in Positive and Negative Symptom Scale (PANSS) scores compared to placebo among patients who met the inclusion criteria for those studies. The present case report describes the use of KarXT in a 34-year-old male with schizoaffective disorder, depressed subtype, and opioid use disorder who would have been excluded from KarXT clinical trials due to extensive prior hospitalizations, multiple recently failed antipsychotic trials, and concurrent psychiatric polypharmacy. KarXT was discussed with the patient after failing to see improvement with multiple other antipsychotic medications, including clozapine, in the inpatient setting. He agreed to start KarXT in addition to the intramuscular paliperidone palmitate, mirtazapine, lorazepam, and trazodone he was already receiving. The patient’s baseline PANSS score was determined to be 86 just prior to his first dose of KarXT. By day 4, his PANSS score decreased to 46, representing a 47 % decrease. At 5 weeks, the patient was reevaluated via phone and determined to have a PANSS score of 52. These findings are an encouraging example of a patient with comorbid psychiatric diagnoses and concurrent medication regimens receiving benefit from KarXT. This case illustrates the potential utility of KarXT in a complex patient population typically excluded from trials, suggesting broader clinical applicability.