The panel also voted 15-0-1 to recommend that the FDA require that the drugs include a medication guide for patients and parents.
All of this controversy was prompted by data that showed that widely prescribed ADHD drugs like Ritalin may be lined to as many as 25 deaths that occurred between 1999 and 2003. Of these deaths, 19 involved children. In addition, the FDA was advised of 54 cases involving serious cardiovascular problems like heart attacks, strokes, hypertension, heart palpitations and arrhythmias in both adults and children taking these medications.
There is also the open issue of another 26 deaths between 1969 and 2003 in medicated ADHD patients involving suicide, intentional overdose, drowning, heat stroke, and underlying diseases.
The panel ˘â‚¬â„˘s vote also caught the FDA off guard because the committee was convened to advise the agency on how to design studies to assess possible risks associated with stimulant ADHD medications.
During the meeting, however, talk soon turned to the over-prescribing of these drugs and the public as well as many doctors were unaware of these serious potential risks. The panel then agreed to consider the enhanced-warning issue that was outside of its planned agenda.
In attempting to lay the foundation for ignoring the panel ˘â‚¬â„˘s vote, officials said they would be reluctant to require a black box warning based on a ˘â‚¬Ĺ“theoretical risk. ˘â‚¬ ť
Such warnings could unreasonably deter patients and doctors from using a drug that could benefit them, said Robert Temple, MD, director of medical policy at the FDA's Center for Drug Evaluation and Research. He stated: "The absence of bona fide problems in your hand pushes against the box. We will also, frankly, worry about the possibility that overstatement can do active harm."
Thus, Temple indicated the full FDA would wait for the recommendation a pediatric advisory committee scheduled for March before reaching any decision with respect to new warnings. That panel, which is made up of pediatricians and psychiatrists, is considered more likely to look favorably on the benefits of ADHD drug treatment as outweighing the potential risks.
These drugs, along with amphetamines like Adderall, Adderall XR, and Strattera, are widely prescribed for the treatment of ADHD. Last year, 7.8 million prescriptions for Concerta and 2.5 million for methylphenidate were written in the United States alone.
While these drugs appear to be effective, they come with relatively serious warning labels. In fact, the FDA posted the following Alert on February 9 in response to Health Canada’s suspension of Adderall XR sales due to a concern about reports of sudden unexplained deaths in children taking both Adderall and Adderall XR.
“FDA ALERT [2/9/2005] – Sudden Deaths in Children
Health Canada has suspended marketing of Adderall XR products from the Canadian market due to concern about reports of sudden unexplained death (SUD) in children taking Adderall and Adderall XR. SUD has been associated with amphetamine abuse and reported in children with underlying cardiac abnormalities taking recommended doses of amphetamines, including Adderall and Adderall XR. In addition, a very small number of cases of SUD have been reported in children without structural cardiac abnormalities taking Adderall. At this time, FDA cannot conclude that recommended doses of Adderall can cause SUD, but is continuing to carefully evaluate these data.”
Thus, the FDA has had every reason to monitor adverse event reports very carefully with respect to all of the drugs used in the treatment of ADHD. Of course, an adverse event report neither identifies a side-effect nor confirms one’s existence. It may truly be something to watch or it may simply be an occurrence unrelated to the drug being taken.
Even when a link to a particular prescription drug is not proven, the FDA and the manufacturer often mention these events on the label. Recent high profile drug withdrawals, pressure from consumer advocacy groups and lawmakers, and a move toward greater disclosure of adverse information about prescription drugs have prompted the FDA to be more proactive in terms of identifying and following potential safety problems.
Recently, the FDA has received reports of patients experiencing a variety of psychiatric events while being treated with Ritalin or Concerta. These include hallucinations, suicidal thoughts, psychotic behavior, aggression, and violent actions. (Eli Lilly has reported observing increased aggression and hostility in a small number of Strattera users and has added that information to the U.S. and European label for the drug.)
As a result of these reports, the FDA plans to strengthen the warning labels on Ritalin, Concerta, and all other methylphenidate products and has also asked its pediatric advisory committee to review the matter. The agency has not confirmed any link between the adverse events and the drugs and it has not indicated that a description of the events will be included in the warning.
Any labeling change, however, is likely to be put off until all ADHD medications are re-evaluated. This would probably not occur until early 2006.
In addition to the possible psychiatric problems associated with the drugs, the FDA is also concerned over reports of cardiovascular problems including hypertension, arrhythmias, chest pain, and tachycardia in Concerta users. As a result, further steps may be taken to investigate these issues by way of data base studies or new safety trials.