Real-World Safety Profile of Xanomeline-Trospium (Cobenfy), the First Muscarinic Agonist Antipsychotic: A Disproportionality Analysis of the FDA Adverse Event Reporting System

Abstract

Preprint (version 2.0, six-quarter update: Q4 2024 to Q1 2026). First real-world post-marketing pharmacovigilance analysis of xanomeline-trospium (Cobenfy) in the FDA Adverse Event Reporting System, applying a four-method disproportionality battery, active-comparator analyses against six D2 antagonists, Weibull time-to-onset modelling, and three-category signal classification. Among 1,758 xanomeline-trospium cases, 64 consensus signals were identified (31 pharmacological, 24 disease manifestations, 9 indeterminate). This version extends the original five-quarter analysis to the full pre-registered six-quarter window and replaces the E-value analysis with an explicit treatment of FAERS reporting and selection biases.