Real-world analysis of gender differences in drug-induced insomnia: evidence from FAERS and CVARDD databases

TL;DR

This study finds that many drugs cause insomnia, with some affecting men and women differently, using real-world data from two databases.

Contribution

The study identifies sex-specific differences in drug-induced insomnia and validates findings across two independent databases.

Findings

237 drugs showed significant insomnia signals, many not listed in their labels.

15 of the top 20 drugs showed sex-specific differences in insomnia risk.

External validation confirmed 124 drugs with consistent insomnia signals.

Abstract

Insomnia is a common sleep disorder that substantially impairs quality of life. Drug-induced insomnia (DII), an important cause of secondary insomnia, is often underrecognized, and many potential signals are not yet documented in drug labels. Evidence regarding sex-specific differences in DII remains limited, hindering the development of tailored safety strategies.

To identify drug–insomnia associations, assess sex-specific differences, validate signals in an independent database, and characterize the time-to-onset (TTO) of high-risk drugs using large-scale real-world pharmacovigilance data.

We conducted a retrospective observational pharmacovigilance study using insomnia-related reports from FAERS (2004Q1–2025Q2). Disproportionality analyses (ROR, PRR, BCPNN, MGPS) were performed, and sex-stratified associations were compared using Wald chi-square tests. Signals were externally validated in the Canadian Vigilance Adverse Reaction Database (CVARDD). Weibull models were applied to evaluate TTO for the drugs with the highest insomnia report counts.

A total of 266,429 insomnia-related reports were identified, with more reports from females (60.1%) than males (32.0%). A total of 237 drugs demonstrated significant disproportionality signals, including several without labeled insomnia risk. Among the 20 most frequently implicated drugs, 15 showed significant sex–drug interactions. Duloxetine exhibited a stronger association in males, whereas niraparib and levothyroxine showed higher risks in females. External validation confirmed 124 overlapping drugs with consistent signals. TTO analyses revealed an early-failure pattern (Weibull β < 1) for all five high-reporting drugs, with median onset ranging from 3 to 211.5 days.

This study identified multiple drug–insomnia signals, quantified sex-specific differences, and validated findings in an independent database. These results underscore the importance of recognizing DII and monitoring sex-related variability in clinical practice.

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