FDA Committee Recommends Warnings on ADHD Drugs

The Food and Drug Administration recently asked a scientific panel to consider ways of studying drugs used to treat attention deficit hyperactivity disorder (ADHD). The drugs studied included amphetamines such as Adderall, and methylphenidates, sold as Ritalin, Concerta, Methylin, and Metadate. Data gathered by the agency’s own studies suggested a link between the drugs and an increased risk of sudden death and serious cardiovascular problems. To confirm their findings, the agency decided to seek outside corroboration from a Drug Safety and Risk Management advisory committee.

A federal health official said that the FDA’s research shows there is a strong possibility that the drugs may be linked to the deaths of 25 people between 1999 and 2003. Of those deaths, 19 were children. The research also discussed 54 cases of serious cardiovascular problems in adults and children being treated with the drugs, including heart attack, stroke, hypertension, palpitations, and arrhythmias. An additional 26 deaths were counted between 1969 and 2003 due to deaths by suicide, intentional overdose, drowning, heat stroke, and other disease.

The FDA's Drug Safety and Risk Management advisory committee reviewed different ways to study whether or not the deaths could be attributable to the use of the ADHD drugs. Some of the patients already had heart problems or high blood pressure, but the findings on the whole warranted further investigation. Dr. David Graham of the FDA explained the concern by saying, "There’s smoke. Does that represent a fire?" Graham added, "Because adults have a higher risk of heart disease and stroke to begin with, any increase in risk caused by these drugs could affect a large number of people."

As a result of the committee’s research, federal science advisors voted 8-7 to recommend that the most stringent type of warning labels be added to containers of Ritalin and other stimulants used to treat ADHD. The committee’s recommendation suggested that manufacturers should add the same type of "black box" safety warnings already used on drugs that can cause potentially fatal side effects. The committee was just an advisory body and the FDA isn’t required to follow their recommendations, but it usually does. Panel member Dr. Curt Furberg cautioned that it would be "inappropriate, unethical behavior" if the FDA decided not to disclose the uncertainty about ADHD drug safety to physicians and patients. The drugs already have warnings related to possible risks to patients with heart defects, but the FDA’s Dr. Gerald DalPan said prior to the votes that the agency felt "this warning is appropriate given our current knowledge of these drugs."

Doctors prescribe ADHD medications to about 2 million children and 1 million adults every month, and those numbers are increasing. According to IMS Health, a pharmaceutical information firm, sales of ADHD drugs increased to $3.1 billion in 2004, from $759 million in 2000. The few studies available providing data on longer-term use of ADHD drugs provide very little information on the risks evaluated by the committee. But analysis of the reports of death and injury suggest a possible link between the drugs and cardiovascular conditions. However, because the link is not conclusive, the FDA’s Dr. Kate Gelperin told the panel that the possible link "is really a question we’d like to have answered."

The Canadian equivalent of the US FDA removed the ADHD drug Adderall XR, a generic version of Ritalin, from their market last year while risk analysis studies were being done. A Canadian panel eventually decided that there was not enough evidence of risk to ban the drug, and the FDA reached a similar conclusion at the same time.