Age-Stratified Safety Signal Analysis of Methylphenidate and Atomoxetine Using Adverse Event Reporting System Database: Children vs. Adults

Objective: The use of Attention-Deficit Hyperactivity Disorder (ADHD) medications has increased markedly in recent years, particularly among adults.This study aimed to detect safety signals associated with methylphenidate and atomoxetine and to compare reporting patterns between pediatric and adult populations using the Korea Adverse Event Reporting System Database (KAERS DB).Methods: Adverse event reports submitted to KAERS from 2020 to 2024 were analyzed.Reports listing methylphenidate or atomoxetine as suspected or concomitant drugs were included.Disproportionality analyses were conducted using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC).Signals were defined when all three criteria were met: PRR ≥2 with χ 2 ≥4 and A ≥3, ROR ≥2 with χ 2 ≥4 and A ≥3, and the lower limit of the 95% confidence interval of IC ≥0.Analyses were stratified by age group (pediatric: 0-18 years; adult: ≥19 years).Results: Among 761,981 adverse event reports, 195 were associated with methylphenidate and 53 with atomoxetine.Disproportionality analysis identified 14 signals for methylphenidate and 5 for atomoxetine.Dissociation was detected for both drugs, whereas urinary tract infection and dysuria were identified only for methylphenidate.These safety signals were not listed in current drug labels and were predominantly observed in adult patients.Conclusion: This study identified potential safety signals associated with ADHD medications using spontaneous reporting data.The detection of previously unlisted safety signals, particularly among adults, highlights the importance of continuous pharmacovigilance and further pharmacoepidemiologic studies to clarify their clinical significance.(PeRM 2026;18:172-182)