Global burden of ADHD medication-associated cardiovascular disease, 1967–2023: A comparative analysis using the WHO pharmacovigilance database

Background

Despite the widespread use of attention-deficit hyperactivity disorder (ADHD) medications and their known sympathomimetic effects on the cardiovascular system, cardiovascular risk assessment of these medications using comprehensive global data is limited. This study investigated the association between individual ADHD medications and cardiovascular disease (CVD) using global pharmacovigilance data.

Methods

Reports from the World Health Organization international pharmacovigilance database were utilized (1967–2023; total reports, n=131,255,418). Reporting odds ratios (ROR), and information components (IC) were calculated to evaluate the association between each medication and specific CVDs.

Results

We identified 13,344 CVD cases related to ADHD medications out of 146,489 cases of all reports on ADHD medications. Cumulative reports on ADHD medications have shown a steady increase, notably in adults since 2010. ADHD medications were associated with a higher risk of CVD overall (ROR [95 % CI], 1.60 [1.58–1.63]; IC [IC_0.25], 0.63 [0.60]), with a higher association observed in females than in males. Among specific CVDs, all drugs were associated with an increased risk of torsade de pointes/QT prolongation, cardiomyopathy, and myocardial infarction. Conversely, heart failure, stroke, and cardiac death/shock were exclusively associated with amphetamines. Lisdexamfetamine showed a weaker association with all CVDs compared to amphetamines, and methylphenidate exhibited the lowest overall association with CVD. Atomoxetine had the second-highest association with torsade de pointes/QT prolongation.

Conclusions

The associations between CVDs and ADHD medications vary, with amphetamines posing a higher risk, while lisdexamfetamine and methylphenidate exhibit better safety profiles.