FEDERAL DRUGS AGENCY STUDY SHOWS RISKS OF METHYLPHENIDATE

The study was published online November 1 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).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 United States and Canada has linked cases of cardiovascular events with these medications, case reports "cannot reliably quantify risk."


Still, on the basis of concerns raised by these findings, in 2008 the American Heart Association recommended that "it is reasonable" to perform electrocardiography 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 Dr. Cooper.


A recent, large observational study, published in May 2011 in Pediatrics and reported by Medscape Medical News at that time, 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 ages 2 and 24 years (mean age, 11.1 years; 71% male) from 4 large health plans: Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology. The mean duration of follow-up was 2.1 years.


This represented "2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs," the investigators note.


ADHD medications used included methylphenidate, dexmethylphenidate, dextroamphetamines, amphetamine salts, atomoxetine, and pemoline.


The primary outcome was a serious cardiovascular event by any of the participants (current ADHD medication users, past users, and nonusers). The types of events examined included sudden cardiac death, acute myocardial infarction, or stroke.


First of 3 Studies


Results showed that 81 serious cardiovascular events were experienced by the study population, including 33 sudden cardiac deaths, 39 strokes, and 9 acute myocardial infarctions.


The adjusted rate of serious cardiac events was not significantly increased for current users of ADHD medications compared with the nonusers (hazard ratio [HR], 0.75; 95% confidence interval [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, no increased risk was found for the specific use of methylphenidate (HR, 0.96; 95% CI, 0.31 - 2.97), "the most frequently used ADHD drug."


Still, Dr. 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 3 "separate but related studies" that it is co-sponsoring with AHRQ to evaluate the potential risk for serious cardiovascular events after the use of ADHD medications. The remaining 2 studies will focus on adults only.


"I think a great next step would be for people that 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 Dr. Cooper.


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