Children and adolescents with attention-deficit/hyperactivity disorder who are prescribed methylphenidate to manage their conditions stand at a higher risk for arrhythmia and other, more serious, cardiac conditions.

In a study published in the BMJ, Ju-Young Shin, Ph.D., and colleagues examined records of 1,224 patients aged 17 years and younger from a nationwide South Korean health insurance database submitted between January 2007 and December 2011. All of the patients had experienced a cardiovascular event and at least one recorded prescription for methylphenidate to treat attention-deficit/hyperactivity disorder (ADHD) ( BMJ 2016;353:i2550 doi:10.1136/bmj.i2550 ).

Of the 1,224 subjects, 864 (70.5%) had experienced arrhythmias, and the mean duration of exposure to methylphenidate was 0.5 years. During periods of methylphenidate treatment, subjects had an increased risk of arrhythmia, as Dr. Shin and coinvestigators calculated an adjusted incidence rate ratio of 1.61 (95% confidence interval, 1.48-1.74). This incidence rate ratio jumped up to 2.01 (95% CI, 1.74-2.31) during the first 3 days of methylphenidate treatment.

The risk was even higher for subjects with congenital heart disease; this subgroup had an adjusted incidence rate ratio of 3.49 (95% CI, 2.33-5.22), compared with 1.34 (95% CI, 1.23-1.46) in patients without it. Both the median age of first exposure to methylphenidate and occurrence of the first cardiac event were in patients aged 11-13 years, reported Dr. Shin of the Centre for Clinical Epidemiology at Jewish General Hospital and McGill University, both in Montreal, and colleagues in Australia and Korea.

“These results are consistent with the biological plausibility that the mechanism of action relates to the effect of methylphenidate on the heart rate,” the authors concluded. “Delayed effects would be expected with myocardial infarction, while more immediate effects would be expected with arrhythmias, as we observed.”

Dr. Shin and colleagues cited several limitations. For example, coding mistakes and incomplete records could not be ruled out in their study. In addition, they said, the “outcome measures were limited to patients with diagnoses of cardiovascular adverse events, and we could have missed outcomes not diagnosed.”

Nevertheless, they said, in light of the increased use of methylphenidate to treat ADHD across the globe, the benefits of using the drug “should be carefully weighed against potential cardiovascular risks of these drugs in children and adolescents.”

Two of the authors disclosed receiving support via fellowships from Australia’s National Health and Medical Research Council.