Identifying Medications Underlying Communication Atypicalities in Psychotic and Affective Disorders : A Pharmacovigilance Study Within the FDA Adverse Event Reporting System

Purpose: Communication atypicalities are considered promising markers of a broad range of clinical conditions. However, little is known about the mechanisms and confounders underlying them. Medications might have a crucial, relatively unknown role both as potential confounders and offering an insight on the mechanisms at work. The integration of regulatory documents with dispropor-tionality analyses provides a more comprehensive picture to account for in future investigations of communication-related markers. The aim of this study was to identify a list of drugs potentially associated with communicative atypicalities within psychotic and affective disorders.Method: We developed a query using the Medical Dictionary for Regulatory Activities to search for communicative atypicalities within the FDA Adverse Event Reporting System (updated June 2021). A Bonferroni-corrected disproportionality analysis (reporting odds ratio) was separately performed on spontaneous reports involving psychotic, affective, and non-neuropsychiatric disorders, to account for the confounding role of different underlying conditions. Drug-adverse event associations not already reported in the Side Effect Resource database of labeled adverse drug reactions (unexpected) were subjected to further robustness analyses to account for expected biases.Results: A list of 291 expected and 91 unexpected potential confounding medications was identified, including drugs that may irritate (inhalants) or desiccate (anticholinergics) the larynx, impair speech motor control (antipsychotics), or induce nodules (acitretin) or necrosis (vascular endothelial growth factor receptor inhibitors) on vocal cords; sedatives and stimulants; neurotoxic agents (anti-infectives); and agents acting on neurotransmitter pathways (dopamine agonists). Conclusions: We provide a list of medications to account for in future studies of communication-related markers in affective and psychotic disorders. The cur-rent test case illustrates rigorous procedures for digital phenotyping, and the methodological tools implemented for large-scale disproportionality analyses can be considered a road map for investigations of communication-related markers in other clinical populations.