Temporal Patterns of Adverse Events Associated With Selective Serotonin Reuptake Inhibitors: A Global Pharmacovigilance Analysis of Early-Onset Versus Late-Onset Toxicity

Background Selective serotonin reuptake inhibitors (SSRIs) are commonly used as first-line antidepressant medications, but adverse events (AEs) remain a common reason for treatment discontinuation. Understanding when these AEs occur can help improve patient care and treatment adherence. Objective This study aims to explore the timing of AEs associated with six commonly used SSRIs: sertraline, fluoxetine, fluvoxamine, paroxetine, citalopram, and escitalopram using global pharmacovigilance data, with a focus on early- versus late-onset profiles. Methods This study analyzed Individual Case Safety Reports (ICSRs) from VigiBase, the World Health Organization's global safety database. Reports were included if an SSRI was the suspected drug and time-to-onset (TTO) data were available. AEs with at least 10 reported TTOs were grouped as early-onset (TTO ≤28 days) or late-onset (TTO >28 days). Results A total of 1,428 AEs met the inclusion criteria. Of these, 914 (64%) were early onset, including nausea (median TTO: 1 day), insomnia and dizziness (2 days), and sexual dysfunction (16.5 days). Late-onset AEs, 514 (36%), included weight gain (31 days), hyperhidrosis (76.5 days), diabetes mellitus (151 days), and osteoporosis (959.5 days). Early AEs were mostly gastrointestinal, neurological, or activation-related; late AEs were largely metabolic or endocrine. Conclusions SSRIs show distinct temporal AE patterns. Early-onset symptoms require timely management to improve tolerability, while late-onset effects highlight the need for ongoing monitoring. These findings can inform personalized monitoring strategies and guide patient counseling to support safer long-term SSRI use.