The cardiac risk of the drugs for ADHD have attracted interest recently following the recommendation by the Drug Safety and Risk Management Advisory Committee of the FDA to include a black-box warning describing the cardiovascular risks of stimulant drugs used to treat this condition. However, this recommendation has subsequently been toned down by the Pediatric Advisory Committee of the FDA.
ADHD (attention deficit hyperactivity disorder) is a disorder mainly diagnosed in school age children. It is characterized by increased activity, an inability to concentrate and poor school performance. Stimulant drugs have been the mainstay of treatment of ADHD. These include amphetamine and related drugs like methamphetamine and methylphenidate (Ritalin).
It is estimated that 2.5 million children now take stimulants for ADHD in the USA. A growing number of adults also take the drug, with a diagnosis of "adult ADHD", which has recently come into vogue. However, the numbers are quite small in Europe and elsewhere.
Now let us come to the crux of the matter. Why are these drugs supposed to cause heart problems?
These stimulant drugs belong to the class of sympathomimetic amines. Cardiovascular effects of these compounds have been well studied. They act by stimulating the sympathetic nervous system and increase heart rate and blood pressure significantly. One study with a commercially marketed formulation showed an increase in systolic BP by about 5 mm Hg in treated adults. Such a rise of BP, argues the Drug Safety and Risk Management Advisory committee, can cause definite adverse effects on long term therapy.
The induced increase in heart rate also has well-described adverse effects on the heart. Persistent increase in heart rate may induce chronic heart failure as demonstrated in animal models of dilated cardiomyopathy.
The Committee also cites the examples of Ephedra (ma huang), marketed as a dietary supplement and phenylpropanolamine, an over the counter nasal decongestant, which belong to the same class. They have been known to have caused several well publicized adverse effects. Studies have reported that ephedra containing supplements accounted for 64% of the serious adverse reactions to supplements reported to the Centers for Disease Control and Prevention, although their sales represented less than 1% of all dietary-supplement sales. A 16-fold increase in the risk of stroke has been reported among women taking phenylpropanolamine as a weight loss drug.
Drug Safety and Risk Management Advisory committee studied cases of myocardial infarction, stroke and sudden death in children and adults taking ADHD stimulants which have been reported to the FDA's Adverse Event Reporting System (AERS). This could represent only a tip of the iceberg as only 1 to 10 percent of serious adverse events are actually reported. Some had evidence of undiagnosed heart disease on autopsy and the documentation was frequently incomplete.
Despite these difficulties, the advisory committee decided to recommend strong preemptive action. Factors which the committee cited as the reason for the action included the tendency of these drugs to raise blood pressure and heart rate, the history of serious adverse effects associated with two drugs of the class (ephedra and phenylpropanolamine) and the rapid increase in exposure,particularly among adults. Though the committee noted important potential benefits of these drugs for certain highly affected children, they felt that the administration of these potent sympathomimetic agents to millions of Americans is inappropriate. The recommendations emphasize more selective and restricted use of these drugs while increasing the awareness of potential hazards.
However, FDA's Pediatric Advisory Committee was of the opinion that adding strong black-box warnings could cause more harm than good and may frighten patients. They, on the other hand, called for new information about health risks on the labels of attention deficit drugs. This would benefit doctors, patients and parents. They said that patients and parents should know about the reports even though it is unclear if the drugs contributed to the problems.
Now, the FDA has to decide on the difficult problem of how to communicate the potential risks associated with ADHD drugs. The FDA will consider both panels' recommendations before making a final labeling decision.
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