ADHD drugs should carry warning, FDA committee recommends

An advisory committee to the US Food and Drug Administration has voted to recommend that black box warnings—the most serious—be put on drugs prescribed for attention deficit hyperactivity disorder (ADHD) because of concerns over cardiovascular effects. Another committee recommended warning doctors and patients that these drugs could cause hallucinations. Both committees recommended information leaflets for patients.

The FDA can accept or reject committee recommendations. A spokesperson for the agency told the BMJ that no decision had yet been made. Details of why the drug safety and risk management advisory committee voted in favour of imposing the strongest warning were explained in an article published last week in the New England Journal of Medicine (2006;354:1445-8).

The article's author, Steven Nissen, a Cleveland Clinic cardiologist and a consultant to the committee, said that the committee had several concerns about the drugs. They include amphetamines and methylphenidate and are closely related members of the class of sympathomimetic amines.

Most of the group thought that “strong and immediate action” was warranted, he said, because of the “propensity of sympathomimetic agents to raise blood pressure and heart rate, the history of serious adverse effects associated with two members of the class (ephedra and [phenylpropanolamine]), and the rapid increase in exposure [to the drugs in the population].” The committee voted by eight to seven in favour of a black box warning and unanimously in favour of a guide for patients.

About 2.5 million US children and 1.5 million adults take these drugs, according to Dr Nissen's article. Nearly 10% of all 10 year old boys in the US take the drugs. Use is much less common in Europe, he wrote. Adult attention deficit hyperactivity disorder “is a relatively recent phenomenon and has resulted in the most rapid growth in the use of such agents,” he said. More than 10% of adults who are taking the drugs for the disorder are over 50.

Twenty five cases of sudden death in children and adults taking the drugs were reviewed by the FDA committee. The reports came through the FDA's voluntary adverse event reporting system, which is thought to greatly under-report adverse events.

Although the drugs may benefit “certain highly dysfunctional children, we rejected the notion that the administration of potent sympathomimetic agents to millions of Americans is appropriate,” Dr Nissen said.

Another FDA committee, the paediatric advisory committee, recommended providing a guide that warns patients that such stimulants cause hallucinations in a small number of children. The hallucinations often involve insects, snakes, or worms. Dr Thomas Newman, an epidemiologist at the University of California, in San Francisco, told the New York Times (23 March, p A23) that two to five out of 100 children treated with the stimulants for a year will experience a serious psychotic episode such as hallucinations.