Ritalin, Adderall and other drugs widely used to treat attention disorders didn't increase the risk of serious heart problems in a major study published Monday that could help ease concerns about the heart-related safety of the medicines.
The drugs, including Shire PLC's Adderall, Johnson & Johnson's Concerta, and Novartis AG's Ritalin, as well as generic versions, are associated with modest increases in blood pressure and heart rate. They are also known to be highly effective in managing ADHD symptoms, with more than 80% of patients responding to the medicines, researchers say.
The findings, from an analysis involving nearly 500,000 adults, come on the heels of a separate study that reached a similar conclusion about the medications' effect in 1.2 million children and young adults. The results don't completely exonerate the drugs, which have other side effects that include a slowing of growth in children and anxiety. But researchers and doctors who treat the condition—known formally as attention deficit-hyperactivity disorder, or ADHD—said that together the reports should generally allay worries about heart risk that have stirred confusion among doctors and patients for several years.
"We don't see any evidence they're increasing risk," said Laura A. Habel, a research scientist at Kaiser Permanente at the big health plan's Northern California operation in Oakland and lead author of the latest study. But she added that the study didn't go as far as to prove the drugs are safe.
About 2.7 million children are prescribed medicines for ADHD, mostly to help control impulsive behavior and an inability to focus and pay attention. More than 1.5 million adults also take the drugs, researchers said. Growth in the medications' use among adults has outpaced that in children during the past decade.
Fears about potential heart risk for ADHD medicines were sparked in 2005 by reports of about a dozen deaths from sudden cardiac arrest among young users of Adderall. The reports prompted the Canadian government to temporarily remove Adderall from the market, though it later lifted the suspension after it was determined that the patients who had died had heart defects or other underlying heart disease.
In the U.S., the Food and Drug Administration held advisory panels to discuss the matter in 2006. The agency subsequently required an update to product labeling to mention cardiac risk. The American Heart Association in 2008 urged that children being considered for ADHD drugs undergo a thorough heart exam, possibly including an electrocardiogram, before taking the medicines.
"Many patients and families stopped using the medicine," said Victor Fornari, director of child/adolescent psychiatry at North Shore-LIJ Health System in New Hyde Park, N.Y. The issue of whether the drugs cause heart problems still "comes up every single day" in discussions with parents of children with ADHD and adult patients, he said.
At the Mayo Clinic, in Rochester, Minn., cardiologist Michael Ackerman said he knows of students who stopped taking the medicines and went from "high-functioning, straight-A students to F students" after doctors became concerned that the drugs "could kill their patients."
Both doctors, who weren't involved with the research, said they hope the new findings provide reassurance to doctors, patients and parents of children with ADHD that the risk of the medicines, especially in otherwise healthy people, is very low.
"The consequences of failure to treat ADHD far outweigh the risk of untreated ADHD," Dr. Fornari said. Children with untreated ADHD usually don't do well in school and adults often can't function in the workplace.
Both the new study, published online Monday by the Journal of the American Medical Association, and the earlier one, published last month by the New England Journal of Medicine, were funded by the FDA and other U.S. agencies to get a clearer picture of the risk associated with the medicines after the 2006 advisory panel hearings.
The study in JAMA compared about 150,000 adult users of ADHD medications between 25 and 64 years old to nearly 300,000 nonusers. Researchers reviewed medical records from four health insurance plans to look at the number of serious cardiovascular events such as sudden cardiac death, heart attack and stroke among both groups.
The study found there were 1,357 heart attacks, 296 cases of sudden cardiac death, and 575 cases of stroke among all patients. The rate was similar among users and nonusers of ADHD drugs, which suggests the drugs didn't increase risk of developing serious cardiovascular problems.
The earlier study, by the same research team, reached a similar conclusion among patients 2 to 24 years old.
Patients evaluated in the studies weren't randomized and the average duration of treatment was relatively short, prompting researchers to say that a potential for increased risk associated with the medicines was possible.
"Even though we can't rule out increased risk," said William Cooper, a pediatrician at Vanderbilt University, Nashville, Tenn., and lead author of the earlier paper, "the absolute magnitude would be low because the [serious] events are so rare."
Despite the findings, the FDA said Monday that patients treated with ADHD medications should continue to be monitored for changes in heart rate or blood pressure as well as for other side effects that include decreased appetite, weight loss and trouble sleeping. The agency also said the drugs "should not be used by patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic."
Mason Turner, regional director of mental health outpatient operations for Kaiser Permanente Northern California, said that with low doses, careful monitoring of blood pressure and other measures, and consultation with a cardiologist, even patients with heart risk who also have significant ADHD symptoms can be effectively treated with the medicines.
Dr. Turner also said strategies that don't involve taking drugs can help some patients. Among these are educating patients to better organize their lives or to ask at school or work for assistance in helping with detailed assignments and projects. That "can mean the difference between doing well or doing poorly," he said.
Reviewed / Posted by: Scott W. Yates, MD, MBA, MS, FACP
