Methylphenidate May Increase Risk of Arrhythmias in Some Youth

Findings from a study published in BMJ Open Access shows that some children and adolescents who are receiving methylphenidate for treatment of attention-deficit/hyperactivity disorder (ADHD) may be at increased risk for certain adverse cardiovascular events.

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Medications to treat ADHD have been shown to be efficacious in reducing symptoms of impulsivity and hyperactivity in children, the study noted, but concerns have been expressed about possible adverse cardiovascular events with the first-line treatment, methylphenidate.

“There has been an increase in the use of drugs for ADHD globally,” said the study’s corresponding author, Nicole Pratt, Ph.D., a senior research fellow at the Sansom Institute for Health Research at the University of South Australia. She told Psychiatric Newsthat research shows that half of the approximately 3.5 million children diagnosed with ADHD in 2011 in the United States received a stimulant drug for treatment, typically methylphenidate.

“No medicine is completely risk free, and our study has identified that there may be excess cardiac risk associated with methylphenidate.”

To determine whether an association exists between methylphenidate and adverse cardiovascular events in youth with ADHD, the team of international researchers analyzed insurance claims data submitted by health care providers of 1,224 individuals from South Korea aged 17 and younger who had experienced a cardiovascular event—such as an arrhythmia, myocardial infarction, or ischemic stroke (in accordance with ICD-10 criteria)—and had received at least one prescription for methylphenidate. Incidence of cardiovascular event was adjusted against time on medication and preexisting cardiovascular conditions.

The analysis showed that overall exposure to methylphenidate was significantly associated with an increased risk of arrhythmias, with the highest risk for such events occurring from one to three days after initiation of medication. Risk for arrhythmias was highest in youth who had congenital heart failure.

For myocardial infarction, risk was significant only from eight days to 56 days after initiating treatment.

No significant increase in risk was observed for hypertension, ischemic stroke, or heart failure. No differences in risks for any outcome were observed between medication doses.

“While the risk of myocardial infarction was not significant overall,” Pratt and colleagues wrote, “we found an increased risk after the first week of treatment, which remained significantly raised for the first two months of continuous treatment. These results are consistent with the biological plausibility that the mechanism of action relates to the effect of methylphenidate on the heart rate. Delayed effects would be expected with myocardial infarction, while more immediate effects would be expected with arrhythmias, as we observed.”

The authors noted, however, that their findings may have been impacted by several study limitations. Among them: antidepressants, antipsychotics, or antiepileptics are often prescribed with methylphenidate and could explain some of the association found with cardiovascular adverse events. Also, while the authors adjusted their analyses for time-varying comorbidities and co-medications, other confounding factors may have been at play. “For example, there might be differences in severity of ADHD symptoms, substance use, and precipitating factors that could have influenced both the occurrence of a cardiovascular adverse event and methylphenidate exposure,” they wrote.

Pratt told Psychiatric News that while the relative risk of cardiac events was found to be significant, the absolute risk is likely to be low because cardiac events are rare in children. Nevertheless, she added, “health professionals should consider the risk-benefit balance of methylphenidate treatment in children with a prior history of heart disease … and regularly monitor blood pressure and heart rate to help mitigate any potential risk.” ■