A Qualitative Investigation of the Experience of Taking Xanomeline and Trospium Chloride for Schizophrenia, Part 2: Perceived Changes in Subjective Quality of Life and Medication Satisfaction

Abstract Introduction The FDA approval in 2024 of the M1/M4 muscarinic receptor agonist xanomeline and trospium chloride (formerly known as KarXT) introduces a novel alternative to dopamine-receptor antagonism or partial agonism for schizophrenia treatment. All prior approved treatments rely on direct D2-receptor antagonism or partial agonism, limiting patient experiences to this mechanism. To explore this shift, we conducted a qualitative study examining patient experiences with a muscarinic receptor agonist. A companion report addresses perceived symptom changes; this report focuses on changes in quality of life (QoL) and medication satisfaction. Methods A qualitative substudy was embedded in a larger 52-week open-label trial of xanomeline/trospium monotherapy in stable schizophrenia outpatients transitioned from standard antipsychotics. It included semi-structured interviews at 6 weeks (n = 70) and 6 months (n = 47) after initiating treatment. Narratives regarding change in QoL attributed to xanomeline/trospium and medication satisfaction were coded and categorized. Results Before starting xanomeline/trospium, most participants reported QoL challenges across the following domains: physical (95.7%), social (85.7%), and role (80.0%) functioning, and emotional well-being (74.3%). For the 2 most common issues in each domain, the percentage of participants who improved by 6 weeks ranged from 44.8% to 83.3%, increasing to 68.0% to 95.2% by 6 months after xanomeline/trospium initiation. Few participants worsened in any of these domains. Participants rated their satisfaction with xanomeline/trospium highly (mean = 8.1 out of 10 at both assessments) and 93.2% would recommend it to a friend. Discussion Xanomeline/trospium treatment was associated with meaningful improvements across QoL domains that participants had previously identified as challenging, and most participants reported high satisfaction with the medication. These findings should be interpreted cautiously given the open-label design, absence of a comparator group, and potential selection and attrition biases. Within these constraints, the results provide exploratory, participant-centered insights into treatment experience and suggest that muscarinic agonists may influence both symptomatic and functional aspects of schizophrenia, warranting further controlled investigation.