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Gene variations explain drug dose required to control seizures

the IGSP Center at Duke University Medical Center and senior author of the study.

"In medicine today, physicians must rely on a one-size-fits-all approach when making decisions about which drug to use and in what dose," Goldstein said. "This study makes clear that such an approach is not sufficient. People with epilepsy are genetically different from one another, and some of those differences affect their responses to drugs in a predictable manner.

"We are beginning to understand how genetics can be applied to medicine in such a way as to reduce trial and error and improve quality of life for patients," he added.

Epilepsy and seizures affect 2.5 million Americans of all ages, with approximately 181,000 new cases diagnosed each year. Phenytoin and carbamazepine are important first-line anti-epileptic drugs that are widely prescribed throughout the world, Goldstein said. Both drugs commonly spur adverse reactions.

"Physicians have long recognized that patients with the same condition differ in their responses to the same drugs," said neurologist and epilepsy specialist Sanjay Sisodiya, M.D., leader of the University College London effort and co-author of the study. "This study establishes the principle that genetic differences between patients do influence variation in response to anti-epileptic drugs for patients with epilepsy.

"In time, we hope to have a number of such gene variants that together can explain and predict more and more of the variation among patients in drug response, allowing better informed treatment decisions," he continued.

Control of epilepsy with phenytoin can be a difficult and lengthy process because of the wide range of doses required by different patients and the drug's narrow therapeutic index, explained study co-author Nicholas Wood, Ph.D., of the University College London. The therapeutic index refers to the ratio between a drug's toxic and therapeutic dose, used as a measure of the drug's r
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Source:Duke University Medical Center


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