BACKGROUND: Experiential negative symptoms (NS) are determinants of disability in schizophrenia (SCZ). Xanomeline/Trospium Chloride (X/T), an M1/M4 muscarinic receptor agonist, is an approved monotherapy for treatment of schizophrenia, including NS. We used remote ecological momentary assessments (EMA) to track changes in indicators of NS during 12 months of outpatient treatment with X/T. METHODS: After discontinuing previous medications, 566 outpatients with SCZ received open-label X/T monotherapy for up to 12 months. Participants completed 3 EMA surveys 7 days a week, one week a month. Surveys queried whether participants were home vs. away and alone vs with someone, as well as productive and unproductive activities, and moods. Hierarchical linear modeling (HLM) examined temporal changes and the relationships between the indicators of NS. RESULTS: 500 participants answered one or more EMA surveys and 350 met 33 % adherence criteria, answering a total of 40,464 surveys, with overall adherence among these participants at 66 %. During treatment with X/T, there were significant decreases in surveys at home (p <
.001), alone (p <
.001), and engaging in unproductive activities (p <
.001). There were significant increases in productive activities both home (p <
.001) and away (p <
.001) and in positive affect (PA) (p <
.001). Improvements in PA converged with reduced unproductive activities, particularly when others were present (p <
.001). CONCLUSIONS: Behavioral indicators of NS improved early and were sustained with X/T treatment. Improvements were multidimensional, shifting toward more time with others, away from home, and engaged in productive activities. These improvements were associated with increases in PA, consistent with previous EMA studies of NS.