Use of methylphenidate and the risk of cardiovascular diseases in children and adolescents with a family history of heart diseases and congenital heart diseases: A self-controlled case series study.

Psychostimulants have been recommended as first-line therapy for attention-deficit/hyperactivity disorder (ADHD), and safety concerns related to cardiovascular events in psychostimulant users have attracted increasing attention. However, evidence remains limited regarding the cardiovascular risks associated with methylphenidate use in children and adolescents who have heart disease or a family history of cardiovascular conditions. We conducted a self-controlled case series (SCCS) study using Taiwan's nationwide insurance database (2004-2021), which links data from births registered in the National Health Insurance system. A total of 2,493 individuals with ADHD, at least one methylphenidate prescription, and incident cardiovascular disease (CVD) were enrolled. A stratified Cox regression model adjusted for time-varying confounders was used to estimate the relative risks (RRs) of arrhythmias, ischaemic heart disease, and cerebrovascular disease during methylphenidate exposure compared with those during unexposed periods. Effect modification by congenital heart disease and family history of CVD was also assessed. We found a significantly increased risk of arrhythmias during both the exposed period (RR: 1.41, 95% CI (Confidence Interval): 1.21-1.63) and the pre-exposed period (RR: 1.50, 95% CI: 1.15-1.96). No significant association was observed between methylphenidate use and the risk of ischaemic heart disease (RR: 0.86, 95% CI: 0.49-1.50) or cerebrovascular disease (RR: 0.79, 95% CI: 0.45-1.39). A family history of CVD did not affect cardiovascular risk. However, individuals with congenital heart diseases had an elevated risk of arrhythmias during the pre-exposed period (RR: 3.19, 95% CI: 1.47-6.94) but not during the exposed period. These findings suggest that methylphenidate use is not significantly associated with ischaemic heart disease or cerebrovascular events in ADHD youth, even those with a family history of CVD or congenital heart diseases. The relationship between methylphenidate and the increased risk of arrhythmias during both the exposed and pre-exposed periods needs further investigation.