Methylphenidate and Long-Term Risk of Cardiovascular Diseases: A Nationwide Cohort Study

Cardiovascular safety of methylphenidate remains a matter of debate.

To evaluate the long-term cardiovascular risk associated with methylphenidate use, a cohort study was conducted using the French National Health Data System. New users were defined by a first methylphenidate dispensation (index date) between January 1, 2014, and December 31, 2023. Each new user was matched with three nonusers by sex and by month and year of birth. Individuals with prior cardiovascular disease or relevant cardiovascular comorbidities were excluded. The primary outcome was cardiovascular disease, defined by International Classification of Diseases codes or antihypertensive drug use. Cox proportional hazards models estimated adjusted hazard ratios (HRs), accounting for demographic and clinical covariates. Negative control outcomes were used to assess residual confounding, allowing the derivation of calibrated HRs and confidence intervals.

A total of 212 216 new users and 636 648 matching nonusers were included. Mean age was 13.7 years and 72% were males. Over a follow-up of ~4 years, 3858 cardiovascular diseases occurred (0.45%): 1960 in new users (9.2 per 1000) and 1898 in nonusers (3 per 1000). The adjusted HR was 2.37 (95% CI [2.21; 2.54]), with a calibrated HR of 1.85 (95% CI [1.55; 2.21]).

The results suggest that methylphenidate use may be associated with an increased risk of cardiovascular diseases. Although the calibrated estimates indicate attenuation due to residual confounding, the association remained statistically significant. This supports recommendations for cardiovascular monitoring during treatment.