No evidence ADHD meds increase cardiovascular risk

Deborah Brauser

November 01, 2011

Boston, MA - Attention-deficit/hyperactivity disorder (ADHD) medications do not increase the risk of serious cardiovascular events, new research shows [1].

A retrospective cohort study of more than one million children and young adults found no significant differences in serious cardiac episodes among those who did not use ADHD medications, current users, and former users. In addition, only 3.1 serious cardiovascular events were found per 100 000 person-years.

Dr William O Cooper

"We feel that this study offers some reassurance that . . . there doesn't appear to be an increased risk for sudden death, heart attack, or stroke in those who use these medications," lead investigator Dr William O Cooper (Vanderbilt University, Nashville, TN) said in an interview.

The study was published online November 1, 2011 in the New England Journal of Medicine and funded by the Agency for Healthcare Research and Quality (AHRQ) and by the US Food and Drug Administration (FDA).

In a statement, the FDA said that it will continue to recommend that clinicians prescribe these medications "according to the professional prescribing label."

"A small to modest increase in risk cannot be excluded. Healthcare professionals should take special note that stimulant products and atomoxetine [Strattera, Eli Lilly] should generally not be used in patients with serious heart problems or for whom an increase in blood pressure or heart rate would be problematic," said Sandy Walsh, from the FDA Office of Public Affairs.

"Patients treated with ADHD medications should be periodically monitored for changes in heart rate or blood pressure [and] should continue to use their medicine for the treatment of ADHD as prescribed by their healthcare professional."

Safety confusion

According to the investigators, 2.7 million American children are prescribed ADHD medications each year.

They note that although previous research from the US and Canada has linked cases of cardiovascular events with these medications, case reports "cannot reliably quantify risk."

Still, based on concerns raised by these findings, in 2008 the American Heart Association recommended that "it is reasonable" to administer an ECG in pediatric patients before prescribing ADHD drugs.

"There's been a lot of confusion for families and for providers about the safety of these medicines. So we set out to do a study that was sufficiently large and sufficiently well-designed to address these issues as carefully as possible," said Cooper.

A recent, large observational study, published in May 2011 in Pediatrics also found no significant increase in cardiac events due to use of ADHD medications. However, it was funded by Shire—a manufacturer of ADHD drugs.

In the current study, computerized records dating from 1986 to 2005 were evaluated for 1 200 438 people between the ages of two and 24 years (mean age 11.1 years; 71% male) from four large health plans. The mean duration of follow-up was 2.1 years.

ADHD medications used included methylphenidate (Ritalin, Novartis), dexmethylphenidate (Focalin, Novartis), dextroamphetamines, amphetamine salts, atomoxetine, and pemoline.

First of three studies

Results showed that 81 serious cardiovascular events were experienced by the study population, including 33 sudden cardiac deaths, 39 strokes, and nine acute MIs.

The adjusted rate of serious cardiac events was not significantly increased for current users of ADHD medications compared with the nonusers (hazard ratio 0.75; 95% CI 0.31-1.85) or for former users vs nonusers (HR 1.03; 95% CI 0.57-1.89).

In addition, there was no increased risk for cardiovascular events when current users were compared with former users (HR 0.70; 95% CI 0.29-1.72), and no increased risk for any of the individual events.

Finally, there was no increased risk found for the specific use of methylphenidate (HR 0.96; 95% CI 0.31-2.97), "the most frequently used ADHD drug."

Still, Cooper said that the families of every child and young person being considered for these medications should work with their healthcare provider to carefully decide what the risks and benefits are, especially for those with serious chronic health conditions.

The FDA reports that this is the first of three "separate but related studies" that it is cosponsoring with the AHRQ to evaluate the potential risk of serious cardiovascular events after the use of ADHD medications. The remaining two studies will focus on adults only.

"I think a great next step would be for people who think about policies related to screenings of children who use these medications to hopefully use this study, along with others, to reach a decision on the best recommendations," said Cooper.

"In other words, we hope this study provides important information to guide some of those policy decisions."

No consensus

Dr Lenard A Adler

"This is a very important study," Dr Lenard A Adler (NYU Langone Medical Center, New York) said in an interview.

"Cardiovascular events in children treated with similar medication have been reported over time. Although these events are dramatic and serious, there have been few large-scale studies that have been able to use comparison groups to examine whether or not these risks are greater than what is seen in the general population," he added.

Adler, who was not involved in the study, said that its most important point is that the number of incidences did not differ between those who were and were not exposed to psychostimulants.

"This doesn't mean that individuals taking stimulant medications for ADHD don't need to be monitored. But there's some comfort in these findings," he said.

He noted that clinical recommendations currently vary in regard to this issue.

"Right now we have some guidelines from the American Heart Association, from the American Academy of Child and Adolescent Psychiatry, and from the American Academy of Pediatrics. And there's no consensus among them. The hope is that this study's findings will contribute to establishing consensus among the guidelines to help parents and also practitioners.

"Overall, I think clinicians should tell families that ADHD is a significant disorder that needs to be treated. And there needs to be a discussion of the potential risks and benefits of all medications considered, especially when treating children," he concluded.

The study was supported by the FDA and by the AHRQ's Department of Health and Human Services. Cooper reports that his organization h as received grants from the F D A and AHRQ. Disclosures for the co authors are listed at . Adler reported that he has done research and consulted for Shire, Eli Lily, and a variety of other companies that manufacture ADHD products; and received royalty payments from NYU for the licensing of ADHD scales. "However, none of those were in conflict with this study," he said.


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