August 28, 2013
Uninformed Neurologists Could Mean Inappropriate Prescribing of Antiepilepsy Drugs

Baltimore, MD—Some 20% of U.S. neurologists are unaware of drug safety concerns associated with antiepilepsy drugs, and their patients are at risk of receiving prescriptions for inappropriate medications, according to new study from the Johns Hopkins University School of Medicine.

The report, which appeared recently in the journal Epilepsy and Behavior, suggests that FDA information about newly discovered safety risks is not getting through to prescribers.

Study authors suggest that, while this research focused on neurologists and drugs to control epilepsy, the findings could have broader implications.

“There is poor communication from the FDA to specialists, and there’s some risk to patients because of this,” said study leader Gregory L. Krauss, MD, a professor of neurology at Johns Hopkins. “Unless it's a major change requiring the FDA to issue a black box warning on a product, important information appears to be slipping through the cracks. We need a more systematic and comprehensive method so that doctors receive updated safety warnings in a format that guarantees they will see and digest what they need to protect patients.”

For the national study, Krauss and his colleagues surveyed 505 neurologists in different types of medical practices between March and July 2012. Questions concerned issues such as new safety risks for antiseizure drugs recently identified by the FDA: increased suicidal thoughts or behavior with newer agents; high risks for birth defects and cognitive impairment in offspring of mothers taking divalproex, marketed as Depakote; and risks for serious hypersensitivity reactions in some patients of Asian descent starting treatment with carbamazepine, marketed as Tegretol.

While neurologists treating 200 or more epilepsy patients a year were most likely to know all of the risks, one in five of the neurologists who responded overall said they were aware of none of the risks.

Krauss said one area that concerned him was a lack of understanding of the potential dangers for certain Asian patients who take carbamazepine to control their seizures. In 2007, the FDA recommended that neurologists screen Asian patients for a specific haplotype before initiating treatment with the medication. In response to the survey, only 70% of the neurologists said they knew of the recommendation.

Carbamazepine treatment was initiated in Asian patients by 147 neurologists responding to the survey, but only 33 of them said they performed haplotype screening. In fact, 18 neurologists reported that, during the time period, some of their Asian patients developed carbamazepine-related hypersensitivity reactions—severe skin rashes that can lead to scarring, blisters in the mouth, and shredding of the skin.

“If their doctors were more educated about the risks,” Krauss says, “these patients may have avoided these severe hypersensitivity reactions.”

In terms of pregnancy risks related to divalproex, fewer than half of the respondents said that they were aware a warning had been issued about high risks of birth defects and of developmental risks in offspring, resulting in an 8- to 9-point drop in IQ. Awareness was higher, 80%, about the FDA’s warning that the risk of suicide with newer drugs is 4.3 per 1,000, double what had previously been believed, and 70% of the neurologists said they counseled patients about the risk.

“Many neurologists commented that the FDA's findings and recommendations are controversial and that knowing the exact risk of ‘suicidality’ (itself a nebulous concept) is not essential to good clinical care,” according to the journal article.

Part of the problem is that neurologists get safety information from a variety of sources, according to the report. “The FDA needs to do better getting the warnings to prescribing doctors,” Krauss said. “There has to be a direct way to communicate risks without overwhelming physicians with messages.”

In general, according to the survey, neurologists said they would prefer receiving FDA safety updates through their specialty organizations.

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