Epilepsy Drug Linked to Lower IQ

Birth Defects Also Greater in Children Born to Women Taking Valproates

From the WebMD Archives

Oct. 13, 2004 -- A widely used group of epilepsy drugs already linked to birth defects is now being blamed for lowering IQ and causing developmental delays in the offspring of women who take them during pregnancy.

Researchers from the U.K. reported significant reductions in IQ scores among children whose mothers took the epilepsy drug sodium valproate (Depakon) during pregnancy. These children's IQs were found to be "in the low average" range.

"The differences between the children exposed to sodium valproate and those exposed to other drugs were not insignificant," epilepsy physician and researcher David W. Chadwick, MD, tells WebMD. "Some of these children were quite disabled in terms of learning and behavioral problems."

A separate study, reported last month by Boston University researchers, strongly linked a similar epilepsy drug - Depakote -- to birth defects. Babies born to mothers taking a generic version of the drug were three to four times as likely to be born with birth defects as babies whose mothers took other epilepsy drugs.

The epilepsy drugs sodium valproate and Depakote are both valproates, but Depakote is prescribed more often in the U.S. Depakote is also used to treat bipolar disorder and migraine headaches.

Clearly More Dangerous

Approximately 25 million women worldwide have epilepsy, and most give birth to healthy children. But because uncontrolled seizures can endanger both mother and child, many pregnant women are advised to stay on their epilepsy drugs during pregnancy.

The two newly published studies clearly showed valproates to be more dangerous for developing fetuses than the other epilepsy drugs evaluated.

The study by Chadwick and colleagues included 41 children between the ages of 6 and 16 who were exposed to valproate in the womb -- 52 were exposed to the epilepsy drug carbamazepine (Tegretol) and 21 were exposed to phenytoin (Dilantin). Forty-nine children were exposed to more than one epilepsy drug; another 80 children were not exposed to any epilepsy drugs.

IQ scores were lower in the valproate children than in those whose mothers took other epilepsy drugs and in unexposed children. Valproate-exposed children had IQ levels that averaged seven points lower than normal, and they were three times as likely as unexposed children to have low verbal IQ scores. The study is published in the latest issue of the Journal of Neurology, Neurosurgery, and Psychiatry.


Researchers also found that women who had frequent tonic-clonic (grand mal) seizures in pregnancy were also significantly more likely to have children with a lower IQ.

Folic Acid May Help Counter Epilepsy Drug Effect

Chadwick and colleagues acknowledged the potential for problems in their findings, and in an accompanying editorial neurologist Simon Shorvon, MD, also urged caution in interpreting them. But he added that women of childbearing years who have epilepsy should be counseled about the potential risks associated with the epilepsy drug valproate.

"The problem is that this is the only drug that works for some types of seizures, so it is not as simple as just switching to another medication," Shorvon tells WebMD. "While the news about valproate is disturbing, it is not absolutely conclusive. Right now all we can do is inform women fully about these studies and their inadequacies."

Diego Wyszynski, MD, PhD, who headed the Boston University research team, tells WebMD that taking large amounts of folic acid may help women who take valproate protect their unborn children from birth defects. He recommends that all women of childbearing age who take the epilepsy drug also take 10 times the recommended daily dose of folic acid -- 0.4 milligrams instead of 400 micrograms.

But he says there is little evidence to support the idea that taking mega doses of folic acid helps protect against the IQ impairment and other developmental delays reported by Chadwick and colleagues.

"If a woman can switch to another drug and control her seizures it might make sense to do so at any time during pregnancy," he says. "The potential damage in terms of malformations occurs early in pregnancy, but this may not be the case with IQ."

WebMD Health News


SOURCES: Adab et al. Journal of Neurology, Neurosurgery and Psychiatry, 2004; vol 75: pp 1575-1583. David W. Chadwick, MD, Walton Centre for Neurology and Neurosurgery, Liverpool, U.K. Simon Shorvon, Institute of Neurology, London. Diego Wyszynski, MD, PhD, assistant professor of medicine, epidemiology and biostatistics, Boston University School of Medicine.
© 2004 WebMD, Inc. All rights Reserved.