Analysis of signals for constipation among antidepressants: Using FDA adverse event reporting database

Introduction: It is estimated that 43% of patients with major depressive disorder discontinue pharmacotherapy due to adverse effects. Evidence suggests antidepressant users may experience constipation. Hence, evaluating the gastrointestinal safety profile of these medications is important, as chronic gastrointestinal conditions can negatively affect quality of life, reduce work productivity, and increase overall health risks. Aim: The aim of the study was to evaluate potential signals of constipation linked to antidepressants in publicly accessible databases, which contain spontaneous reports of adverse drug events. Material and Methods: This secondary research study utilized publicly accessible pharmacovigilance databases including the Food and Drug Administration Adverse Event Reporting System (FAERS), VigiBase accessed via the VigiAccess portal, and the EudraVigilance database established by the European Medicines Agency. Disproportionality analyses for constipation were conducted using the reporting odds ratio (ROR), Yule's Q, proportionality reporting ratio (PRR), and information component (IC). Results: Among antidepressants, the strongest signals for constipation in descending order were nortriptyline (ROR=8.89), nefazodone (ROR=4.21), amitriptyline (ROR=4.05), trimipramine (ROR=4.01), amoxapine (ROR=3.96), fluvoxamine (ROR=3.74) and duloxetine (ROR=3.63). Antidepressants with weak signals were escitalopram, fluoxetine, sertraline, agomelatine, bupropion, desvenlafaxine and milnacipran. Conclusion: Clinicians must consider a patient's pre-existing risk factors for constipation and be aware that antidepressants differ in their tendency to cause constipation. Hence, antidepressants with the lowest chance of causing constipation, such as escitalopram, fluoxetine, sertraline, and bupropion - may be preferred.