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THE NATION
February 10, 2006
An FDA panel cites heart risks in its advisory on Ritalin and similar medications.
By Ricardo Alonso-Zaldivar, Times Staff Writer
WASHINGTON — A Food and Drug Administration advisory panel Thursday urged that the strongest possible safety warning be issued for drugs used by millions of children and adults to treat attention deficit hyperactivity disorder, because of emerging concern that they may increase the risks of heart attacks, strokes and sudden death.
The FDA had called the drug safety experts together to help design further research into such risks. But in an unexpected twist, the committee concluded that the evidence of serious risks was so great that a strong new warning — not just more research — was needed.
"This is out-of-control use of drugs that have profound cardiovascular consequences," said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic and member of the panel. "We have got a potential public health crisis. I think patients and families need to be made aware of these concerns."
Although ADHD is commonly associated with children, members of the safety panel emphasized that the drugs could pose a greater danger to adults. The FDA has received reports of about 25 deaths linked to the drugs and of a larger number of cases involving serious health consequences, such as heart attacks.
The panel voted, 8 to 7, to call for a "black box" warning on literature distributed with the drugs — which include well-known brands such as Ritalin, Adderall and Concerta. As many as 4 million Americans take the medications, and government figures show that about 10% of all 10-year-old boys in the United States get the drugs; about 4% of girls that age use them.
"No one is saying that there aren't children who are desperately dysfunctional and need these drugs," Nissen said. "But it isn't 10% of 10-year-olds."
The safety experts also voted unanimously to recommend that a brochure be provided to patients and families to inform them in greater detail about the risks and benefits of using the drugs. And it urged the FDA to expedite studies to better understand the drugs' effects.
Senior FDA officials said that they would study the panel's recommendations and that they planned to refer the issue to another advisory committee dealing with psychological problems in children. The agency has been criticized in the past as being slow to respond to evidence of health risks associated with medications, including painkillers and antidepressants.
"You don't want to over-scare people and make them not use an important drug," said Dr. Robert Temple, a top policy official at the FDA. "But you don't want people using drugs if they don't have to."
Drug makers said Thursday that the attention deficit medications were safe when taken as directed. They noted that some had been in use for more than 50 years.
Shire Pharmaceuticals Group, the maker of Adderall, said that it would work with the FDA to make sure patients had the necessary information, but that stronger warnings were not needed. Novartis, which makes Ritalin, said it had reviewed its own data and had not seen any increase in heart risks for patients.
The companies suggested there probably were other explanations for the deaths and serious health issues reported to the FDA, such as heart problems that had gone undetected before the patient began taking the medication.
Most of the attention deficit drugs are derived from powerful stimulants, including amphetamines. They are believed to help patients concentrate, though exactly how they work is not clear. But they also raise blood pressure, a major risk factor for heart disease and stroke.
Attention deficit hyperactivity disorder can make it difficult for children to apply themselves in school; adult patients may have trouble with multi-tasking. In the United States, about 2.5 million children and 1.5 million adults are taking medication for the condition.
The drugs have been widely prescribed for children since the 1990s, but their use to treat adults is relatively new. Prescriptions written for adults increased by 90% from 2002 to 2005. And the risks for adults may be greater, since high blood pressure and heart conditions are more prevalent among adults.
Currently, 10% of those taking ADHD drugs are 50 or older.
FDA officials convened Thursday's meeting amid concerns about the drugs' potential health problems.
"We wouldn't be going through this exercise if we didn't think there was a real possibility of an increase in risk," said Dr. David Graham, the FDA drug safety investigator who was one of the first to call attention to the heart risks of Vioxx, a leading painkiller withdrawn from the market in 2004. "There's smoke. Does that represent fire, or not? We want to answer that question."
The risks appeared to be different for children and adults. Graham and his colleagues undertook a preliminary study using information in the databases of large health insurers and government programs.
Their early findings indicated a higher-than-expected number of heart attacks and strokes among adults taking the medications. Among children through age 18, the number of strokes was higher than expected, but the number of heart attacks was lower.
Not all ADHD drugs are the same. Strattera, made by Eli Lilly & Co., is not classified as a stimulant. But several panel members said the warnings should apply to the entire class of drugs, without exception. That might help put a brake on over-prescribing, they said.
Panel member Thomas Fleming, a biostatistician at the University of Washington, suggested that the heart risks of attention deficit drugs might be comparable to those of the painkiller Vioxx and other so-called Cox-2 inhibitors.
"While there is a lot of focus on children the numbers tell me that the magnitude of the excess risk is quite profound in adults," Fleming said.
For adults to continue taking ADHD drugs, the benefits of therapy would have to be shown to be substantial, he said. But some panel members said the benefits and risks of the medications for adults had not been extensively studied.
Temple, the FDA policy official, said agency officials would discuss internally how to address the problem of the emerging risk for adults.
The committee members suggested several types of studies to look at safety issues for all patients. One option would be to pore through the databases of insurers, as Graham's preliminary study had done. Another would be to compare heart function in patients taking ADHD medications with that of people who have similar characteristics but don't take the medicines.
Such studies might take two years or more to complete.
The FDA's database of reports of adverse drug reactions is not thought to be complete enough to base a study on it. Experts estimate that 1% to 10% of serious drug reactions are reported to the agency.
Canada halted sales of Adderall last year after health authorities there received 20 reports of sudden deaths in patients. But the drug was allowed back on the market after statistical studies indicated it was no riskier than other medications. It is not recommended for patients with underlying heart problems, however.
