Age-stratified safety signal mining of ADHD medications in pediatric populations using the FAERS database (2014-2024): a pharmacovigilance study using multi-method disproportionality analysis.

BACKGROUND

Pediatric attention-deficit/hyperactivity disorder (ADHD) medications have been analyzed in the FDA Adverse Event Reporting System (FAERS), yet systematic age-stratified signal profiling under ICH E11(R1) developmental categories, covering the recently approved agents viloxazine and serdexmethylphenidate, remains unreported.

METHODS

We performed a retrospective disproportionality analysis of pediatric (age <18 years) FAERS reports, 2014Q1-2024Q4, after FDA-standard three-step deduplication. Ten active ingredients (eight in the main analysis, two in a new-drug branch) were identified. Reporting odds ratios (ROR), proportional reporting ratios (PRR), information components (IC, Bate 1998 uniform prior), and empirical Bayesian geometric means (EBGM, DuMouchel 1999) were computed. A signal was classified as Strong when positive across all four methods. Seven prespecified sensitivity analyses were conducted.

RESULTS

Among 15,301 pediatric ADHD cases, 100 Strong signals were identified (71 in adolescents, 29 in children). α2-agonists accounted for 79/100 (clonidine-ER 52, guanfacine-ER 27). A novel dextroamphetamine-posterior reversible encephalopathy syndrome (PRES) signal was reproducible across three independent sensitivity analyses. Methylphenidate showed no Strong signals under within-class or full-pediatric comparators.

CONCLUSION

Distinct age-specific safety signals emerged for ADHD medications, with dextroamphetamine-PRES warranting targeted pharmacovigilance attention.