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Abstract
Roluperidone has proven efficacious for treating negative symptoms of schizophrenia in phase 2b and phase 3 clinical trials. Using network analysis, we demonstrated that the improvements observed in the phase 2b trial resulted from targeting avolition. The current study aims to replicate these network findings using the phase 3 data. Participants included 496 schizophrenia patients who were randomized to roluperidone 32 mg/day (n =167), 64 mg/day (n = 162), or placebo (n = 167). Negative symptoms were assessed at baseline and weeks 2,4,8, and 12. Network intervention analysis (NIA) evaluated treatment-induced symptom changes over time to identify treatment effects. NIA indicated that the 64 mg/day dose of roluperidone had a direct effect on avolition, suggesting changes in avolition propels treatment effects across the entire negative symptom constellation. These findings replicated the phase 2b findings, indicating roluperidone achieves its effect by influencing the extent to which avolition drives other negative symptoms.