Age-stratified signals and early onset of adverse events with pregabalin: a disproportionality analysis of the FDA adverse event reporting system.

INTRODUCTION

Pregabalin is widely used in the management of neuropathic pain and generalized anxiety disorder. However, comprehensive real-world evidence regarding its neuropsychiatric safety profile and age-specific risk variations remains insufficient.

METHODS

Data were retrieved from the FDA Adverse Event Reporting System (FAERS) from Q1 2005 to Q1 2025. Four disproportionality algorithms-reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM)-were utilized to identify safety signals. The Weibull distribution model characterized the time-to-onset (TTO) of adverse events (AEs) and compared risks across age subgroups.

RESULTS

After analyzing 98,196 pregabalin-related reports, 279 preferred terms generated consistent signals using all four disproportionality methods. Confirmed AEs included dizziness, weight increased, and somnolence. Unexpected signals were identified, such as hypoacusis, dysgraphia, logorrhoea, and feeling of despair. Age-stratified analysis revealed that older adults (≥65 years) showed higher risks for falls, and balance disorder. In contrast, adults (18-64.9 years) more frequently reported withdrawal syndrome, drug dependence, and suicidal ideation. The TTO analysis revealed that 54.53% of AEs emerged during the initial month of treatment. The median onset was shorter in older adults (16 days) than in adults (30 days). The Weibull shape parameters (β) for both groups were below 1 (0.46 and 0.48, respectively), indicating an early failure type.

CONCLUSION

This study identifies novel safety signals and distinct age-related risk patterns. Vigilant monitoring during the initial treatment phase is essential, particularly for neuropsychiatric stability and physical safety in vulnerable populations.