Collaborative Study Should Clarify Cardiovascular Sequelae of ADHD Drugs

The Food and Drug Administration (FDA) has announced a joint study with the Agency for Healthcare Research and Quality (AHRQ) on the cardiovascular risks of drugs widely used to treat attention-deficit/hyperactivity disorder (ADHD).

In February 2006, a Drug Safety and Risk Management Advisory Committee recommended to the FDA that black-box warnings be added to ADHD drug labels regarding the risks of heart attacks and other cardiovascular events. In March 2006, however, a Pediatric Advisory Committee concluded that the available safety data from clinical trials and postmarketing surveillance at that time did not warrant black-box warnings (Psychiatric News, March 3, 2006; April 21, 2006). Instead, the pediatric panel recommended revisions to the drug labels and a medication guide for patients; these recommendations were subsequently carried out in 2006.

Now, a new collaborative study, which is a continuation of a project initiated by the FDA in 2006, will coordinate the data analyses under contract with AHRQ's Effective Health Care program. Researchers from Vanderbilt University will examine the medical data of 500,000 patients who took ADHD drugs in a seven-year period through 2005, with information ranging from prescription drug use to deaths.

“We are pleased that the FDA will be able to carry out this postmarketing evaluation of ADHD medications with the AHRQ,” said Darrel Regier, M.D., M.P.H., director of APA's Division of Research and executive director of the American Psychiatric Institute for Research and Education.“ In areas where controversy about medication safety exists, the only appropriate method for resolving such issues is with a rigorous peer-reviewed research design. Collaboration on such evaluations involving the FDA and other federal agencies is an excellent approach for improving our knowledge base for patients and clinicians.”

The collaborative data analyses will include all approved drugs used to treat ADHD in pediatric and adult patients. This is the largest study ever to evaluate cardiovascular risks of ADHD medications, according to the FDA. The findings are expected to clarify the collective safety profiles of ADHD drugs and possible differences among drug classes and patient populations. It is thought that adults may be at higher cardiovascular risks than children, but the evidence is limited.

“This study is necessary to help make logical decisions about these medications,” Steven Nissen, M.D., chair of the Department of Cardiovascular Medicine at Cleveland Clinic Foundation, told Psychiatric News. Nissen was a consultant to the FDA Drug Safety and Risk Management Committee in 2006 and recommended the addition of black-box warnings for ADHD drug labeling. He cited data that suggest as many as 10 percent of ADHD patients are 50 years or older and pointed out that understanding the cardiovascular risks is relevant to pediatric as well as adult patients, considering the long-term use of these medications.

Data from a study published in the March-April Health Affairs indicated that global use of ADHD medications increased threefold from 1993 to 2003. Estimated prevalence of ADHD is 3 percent to 5 percent among school-age children and 4 percent in adults, according to the National Institute of Mental Health.

A press release on the FDA and AHRQ collaborative study is posted at<www.fda.gov/bbs/topics/news/2007/new01568.html>. An abstract of “The Global Market for ADHD Medications” is posted at<http://content.healthaffairs.org/cgi/content/abstract/26/2/450>.▪