Gastrointestinal adverse events associated with SNRIs: A FAERS-based pharmacovigilance study

Abstract

Major depressive disorder is a prevalent mental illness, with SNRIs constituting a mainstay of the psychopharmacological approach to its clinical management. Despite their impact on adherence, efficacy, and relapse risk, gastrointestinal adverse events (AEs) linked to SNRIs remain under-explored. This study systematically evaluated gastrointestinal adverse events associated with SNRIs by leveraging the FDA Adverse Event Reporting System (FAERS) database. A retrospective analysis of FAERS data from 2004 to 2024 identified 114,148 reports involving five SNRI drugs (venlafaxine, desvenlafaxine, milnacipran, levomilnacipran, and duloxetine). Gastrointestinal adverse events ranked among the top ten System Organ Classes for all five drugs. At the pharmacovigilance level, we identified 18 positive signals, with significant risks for five specific adverse events: constipation, dry mouth, oral hypoaesthesia, nausea, and vomiting. Descriptive analyses revealed that middle-aged (45-64 years) and elderly (65-74 years) patients were more susceptible to gastrointestinal adverse events compared to younger age groups, although the specific effects varied across different drugs and age groups. These findings highlight the significant risks of gastrointestinal AEs associated with SNRIs, underscoring the need for individualized drug selection, close monitoring, and further research into underlying mechanisms and long-term impacts.

Keywords: FAERS database; Gastrointestinal adverse events; MDD; SNRIs.