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

## TL;DR

This study analyzes when common side effects of antidepressants called SSRIs occur, finding that some appear quickly while others develop over time.

## Contribution

The study identifies distinct early- and late-onset adverse event patterns for SSRIs using global pharmacovigilance data.

## Key findings

- Early-onset adverse events include nausea, insomnia, and dizziness within the first few days of SSRI use.
- Late-onset adverse events like weight gain and diabetes develop over weeks to months of SSRI treatment.
- Early AEs are mostly gastrointestinal or neurological, while late AEs are metabolic or endocrine-related.

## Abstract

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.