A randomized controlled laboratory study on the long-term effects of methylphenidate on cardiovascular function and structure in rhesus monkeys

James D. Wilkinson, Ralph Callicott, William F. Salminen, Satinder K. Sandhu, James Greenhaw, Angel Paredes, Kelly Davis, Yvonne Jones, Merle G. Paule, William Slikker, Paolo G. Rusconi, Jason Czachor, Amy Bodien, Joslyn A. Westphal, Danielle D. Dauphin, Steven E. Lipshultz

Research output: Contribution to journalArticlepeer-review

Abstract

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 (Macaca mulatta) approximately 7 years of age that had been randomly assigned to one of three MPH dosages: vehicle control (0 mg/kg, b.i.d., n = 9), low dose (2.5 mg/kg, b.i.d., n = 9), or high dose (12.5 mg/kg, b.i.d., n = 10). Dosage groups were compared on serum cardiovascular and inflammatory biomarkers, electrocardiograms (ECGs), echocardiograms, myocardial biopsies, and clinical pathology parameters following 5 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, ECGs, echocardiograms, or myocardial biopsies. The high-dose MPH group had a lower serum myoglobin concentration (979 ng/mL) than either the low-dose group (1882 ng/mL) or the 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.

Original languageEnglish (US)
Pages (from-to)398-404
Number of pages7
JournalPediatric Research
Volume85
Issue number3
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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