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

Abstract

Preprint version 3.1, corresponding to the second-round revision submitted to Schizophrenia Bulletin. 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 2,154,103 deduplicated FAERS cases, 1,758 listed xanomeline-trospium as a suspect drug and 64 consensus signals were identified (31 pharmacological, 24 disease manifestations, 9 indeterminate) across 179 drug-event pairs tested. Change from version 3.0: correction to the case-selection flow diagram (Figure 1) only. The exclusion step had reported the count of cases carrying a concomitant record for the index drug, labelled "concomitant role only". That count includes cases which also carry a suspect record, so it both mislabelled the quantity and did not balance (1,779 - 16 does not equal 1,758). The exclusion is now the complement of the primary/secondary-suspect set, broken down by role: 21 cases, being 15 concomitant-only and 6 interacting-only, so that 1,779 - 21 = 1,758 exactly. Interacting-role cases were previously unrepresented. The figure has also been rebuilt in Mermaid for legibility. No analysis, method, or reported estimate changed, and no other figure, table, or passage of text differs from version 3.0.