Use of methylphenidate and reporting of valvular heart disease: Global pharmacovigilance analysis in children and adults.

ABSTRACT

INTRODUCTION: Methylphenidate (MPH) is a common treatment of attention-deficit/hyperactivity disorder (ADHD). Concern has been raised regarding its cardiovascular safety, partly in relation with its micromolar affinity for the 5-HT2B receptor, whose activation may result in valvular heart disease (VHD). METHODS: To explore the association between the use of MPH and VHD reporting, we performed a disproportionality analysis within the WHO global safety database (VigiBase) using data, since inception until March 6th 2024, from (i) the full database and (ii) different age groups (children/adolescents 6-17 years; adults 18-64 years). To avoid competition bias, safety reports with amphetamine-like appetite suppressants were excluded. Disproportionality was expressed using reporting odds-ratio (ROR) and its 95% confidence interval (CI). RESULTS: Of 29 129 spontaneous reports with MPH, 23 VHD cases (7.9 per 10 000 reports) were identified, including 13 adults and 10 children. Most cases concerned injury on the mitral valve. A disproportionate reporting was observed overall (ROR 1.6, 95% CI 1.1-2.4). Analysis according to age group found that disproportionality in VHD reporting was found in adults only (ROR 2.7, 95% CI 1.6-4.7) but not in children/adolescents (ROR 1.7, 95% CI 0.9-3.2). Furthermore, amongst MPH users only, VHD reporting was higher in adults compared to children (ROR 2.7, 95% CI 1.2-6.3). CONCLUSION: VHD reporting appears rare with MPH compared to other adverse events and is increased in adults only. Our findings support a potential safety signal of VHD in adults exposed to MPH. A risk in that population cannot be excluded and requires further assessment.