A Randomized Controlled Laboratory Study on the Long-Term Effects of Methylphenidate on Cardiovascular Function and Structure in Rhesus Monkeys

BACKGROUND: Whether long-term methylphenidate (MPH) results in any changes in cardiovascular function or structure can only be properly addressed through a randomized trial using an animal model which permits elevated dosing over an extended period of time. METHODS: We studied 28 male rhesus monkeys (M. mulatta) approximately seven years of age who had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, bid, n = 9), low-dose (2.5 mg/kg, bid, n = 9), or high-dose (12.5 mg/kg, bid, n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECG), echocardiograms, myocardial biopsies, and clinical pathology parameters following five years of uninterrupted dosing. RESULTS: With the exception of serum myoglobin, there were no statistical differences or apparent dose response trends in clinical pathology, cardiac inflammatory biomarkers, ECG’s echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/ml) than either the low dose (1882 ng/ml) or control group (2182 ng/ml). The dose response was inversely proportional to dosage (P = .0006). CONCLUSIONS: Although the findings cannot be directly generalized to humans, chronic MPH exposure is unlikely to be associated with increased cardiovascular risk in healthy children.