Early Release of Dr. Nissen's NEJM Article: "ADHD Drugs and Cardiovascular Risks"
Cardiologist Steven E. Nissen believes that Shire Plc's Adderall, Novartis AG's Ritalin, and other drugs used to treat attention deficit-hyperactivity disorder (ADHD) may cause potential risks to the heart, and that these risks should be set forth in a "black-box" warning to heighten the awareness of doctors and patients. Dr. Nissen is the interim chair of cardiology at the Cleveland Clinic and president of the American College of Cardiology.
On March 20, 2006 The New England Journal of Medicine (NEJM) published on its web site an "early-release" version of a "Perspective" article written by Dr. Nissen entitled "ADHD Drugs and Cardiovascular Risk". This article, which will appear in the April 6, 2006 edition of the NEJM, takes us through the thought process that led Dr. Nissen to introduce his black-box warning motion at the February 9, 2006 meeting of the FDA's Drug Safety and Risk Management Advisory Committee. This 15-member panel of experts voted 8 to 7 in support of Dr. Nissen's motion and, thereby, recommended a black-box warning be put on the respective labels, or package inserts, to describe the cardiovascular risks of stimulant drugs like Adderall and Ritalin used to treat ADHD.
Likely not by coincidence, the early release of Dr. Nissen's NEJM article on March 20 came just two days before the FDA convened an advisory panel of pediatricians which will consider the safety of drugs like Ritalin and Adderall. This FDA advisory panel is set to review data on a possible link between the ADHD drugs and cardiovascular problems like heart attacks and strokes, as well as psychiatric problems such as hallucinations and psychosis.
As background, the advisory panel of drug safety experts that met in February 2006 had been asked by the FDA to assist the agency in deciding what kinds of studies needed to be done to further study the side effects associated with Adderall, Ritalin, and the other ADHD drugs. Dr. Nissen suggested that while further studies were warranted, something else was needed immediately -- a black-box warning about the reports of heart attacks, strokes, and sudden unexplained death (SUD) in children and adults that had been submitted to the FDA's MedWatch program.
"That's not the wrong thing to do," [Dr. Nissen] said in February. "I don't care what their benefits are." Nissen says he is proposing a new regulatory standard: That patients should be warned if there is a high level of suspicion that a drug might be dangerous, instead of waiting for definitive proof. "I am convinced we need to warn earlier and then back off the warnings if the drugs prove safe," he says.
The FDA, however, has said several times since the February 2006 meeting -- when Dr. Nissen's black-box warning motion was narrowly passed -- that the agency would wait to hear from this second advisory panel before deciding whether to strengthen or update warnings on the ADHD drug labels.
At the February 2006 advisory panel meeting, there was testimony presented that 2.5 million children currently take one of the ADHD drugs, including almost 10% of ten-year-old boys. Furthermore, 1.5 million adults take ADHD drugs, with a remarkable 10% over the age of 50.
While most concern to date has been focused on the children, for Dr. Nissen it is older users of ADHD drugs that he is particularly worried about as regards the risks of heart attacks and strokes. The substantial increases in heart rate and blood pressure caused by use of ADHD drugs, particularly during long-term therapy as seen in these adults, are known generally to increase morbidity and mortality.
(Posted by: Tom Lamb)