Abstract Introduction Xanomeline and trospium chloride (formerly KarXT) is a muscarinic M1 and M4 receptor agonist recently approved for the treatment of schizophrenia in adults. Unlike all previously approved antipsychotics, it does not directly block dopamine D2 receptors. Given its novel mechanism of action, understanding patients’ subjective treatment experiences, including perceived symptom changes, is clinically important. Methods This is a qualitative study embedded within a larger 52-week open-label long-term safety study that investigated patient perspectives on xanomeline/trospium monotherapy in clinically stable outpatients transitioned from previous antipsychotic treatments. A subsample completed up to 2 semi-structured interviews to explore their experience – favorable or unfavorable – approximately 6 weeks (n = 70) and 6 months (n = 47) post-initiation. Thematic analysis was applied to interview transcripts. Results At study entry, most participants reported symptoms despite ongoing antipsychotic treatment, including positive (auditory hallucinations, 80%), negative (low motivation, 70%), and cognitive (trouble concentrating, 70%) symptoms. Over 60% reported meaningful improvement in one or more symptoms within 6 weeks of starting xanomeline/trospium, increasing to about 80% by 6 months. Less than 10% reported symptom worsening at either timepoint. Participants described these improvements as personally meaningful, with notable benefits in daily functioning. Discussion Participants entered this study with various persistent, burdensome schizophrenia symptoms despite ongoing treatment. Most experienced substantial and sustained symptom relief for up to six months after initiating xanomeline/trospium treatment. These qualitative findings highlight xanomeline/trospium’s potential to provide meaningful relief across multiple symptom domains and support functional recovery. A companion report explores quality of life and medication satisfaction.
Kern et al. (2026) studied this question.