Comparison of serious adverse effects of methylphenidate, atomoxetine and amphetamine in the treatment of ADHD: an adverse event analysis based on the FAERS database.

BACKGROUND: Methylphenidate, atomoxetine, and amphetamine are the most commonly prescribed medications for ADHD, approved by the FDA. Despite their widespread use, real-world studies on their serious adverse effects are limited. This study leverages the FAERS database to analyze the safety of these drugs.

METHODS: A retrospective analysis was conducted using FAERS data from 2004 to 2023. Adverse event (AE) signals for methylphenidate, atomoxetine, and amphetamine were identified by calculating reporting odds ratios (RORs), proportional reporting ratios (PRRs), information components (ICs), and empirical Bayesian geometric mean (EBGM).

RESULTS: The analysis included 72,298 reports, with 37,471 linked to methylphenidate, 17,335 to atomoxetine, and 17,492 to amphetamine. Significant AE signals were found, especially in psychotic disorders for methylphenidate (ROR = 4.47, PRR = 3.7) and amphetamines (ROR = 4.06, PRR = 3.43), and psychiatric and reproductive disorders for atomoxetine (ROR = 5.44, PRR = 4.29; ROR = 2.49, PRR = 2.46). At the PT level, the most common adverse safety signals for the three ADHD drugs were Application site erythema, Somnolence, and Headache. Further analysis showed that "Aggression", "Mydriasis", "Trichotillomania" and suicide-related adverse reactions showed strong signals in the three ADHD drugs. However, there are also differences between the three ADHD medications. For example, serious adverse effects related to cardiovascular and neurological effects were stronger in amphetamines, with the "coronary artery dissection" and "carotid artery dissection" signals being the most significant; "Precocious puberty" has a stronger signal in methylphenidate, and the signal associated with elevated liver enzymes is strongest in atomoxetine. In addition, we also found some PTs that were not included in the drug label, such as "Disturbance in social behaviour" and "Trichotillomania".

CONCLUSIONS: In this study, pharmacovigilance analysis of methylphenidate, atomoxetine, and amphetamine was performed using the FAERS database, and we identified significant safety signals. Of note, three ADHD medications are associated with suicide-related signals, amphetamine associated with coronary artery dissection, methylphenidate associated with precocious puberty, and atomoxetine associated with testicle, penile lesions, and liver damage, which require special attention. This study provides a reference for the clinical personalized medication of ADHD patients.