The anti-seizure drug Depakote (search) has been linked to birth defects and lower IQs among children exposed to it in the womb, but millions of American women may be taking it without knowing the risks, a group of epilepsy experts warned Tuesday.

Officials with the Epilepsy Foundation and the American Epilepsy Society said as many as 15 million prescriptions for anti-seizure drugs are written each year to women in their childbearing years. The drugs are commonly used to treat migraine headaches (search) and bipolar disorder (search) in addition to epilepsy (search).

Depakote is one of the most widely prescribed anti-seizure drugs. In one ongoing study, one in four children born to mothers who took the drug during pregnancy experienced serious adverse events including birth defects and developmental delays. That compared to an adverse event rate of around 10 percent in children exposed in the womb to the antiseizure drug Tegretol and a 1 percent adverse event rate among children exposed to the drug Lamictal (search).

“While our study is not definitive, it certainly raises serious concerns,” principal investigator Kimford J. Meador, MD, said at a news conference on Tuesday. The briefing was held at the American Epilepsy Society’s annual meeting in New Orleans.

Meador said six other studies and national registries of anti-seizure drug users found that the highest rate of birth defects occurred among children born to Depakote users. He added that the clinical evidence is strong enough to argue against the drug’s use as an initial treatment for women who might become pregnant.

“That is not to say that [Depakote] shouldn’t be used by these women at all,” he said, adding that the drug may be the only option for some women since it is often prescribed for the most hard-to-control seizures.

Getting the Answers

In addition to Depakote, there are increasing concerns about the safety of the barbiturate phenobarbital (search), which is also used to control seizures. The panel of experts said these two drugs are the most “worrisome” of the large group of medications used in the treatment of epilepsy, but they added that the safety of most other drugs is not known.

Studies do suggest that the risk of birth defects and mental problems among babies born to women taking Lamictal is no greater than among the general population of pregnant women. Lamictal manufacturer GlaxoSmithKline sponsored Tuesday’s news briefing. GlaxoSmithKline is a WebMD sponsor.

The news conference was held, in part, to urge pregnant women on anti-seizure drugs to participate in a national registry designed to clarify the risks and benefits of the medications. So far, 4,000 women taking 21 different medications have enrolled in the North American Antiepileptic Drug Pregnancy Registry, but conference organizers said much larger numbers are needed to get the answers they need.

The toll free number for the registry is (888) 233-2334, and the hotline is available in both Spanish and English-language versions.

Neurologist Martha J. Morrell, MD, has been treating women with epilepsy for 18 years. She said Tuesday that for years she had no answer when her pregnant patients asked if the drugs they were taking would harm their babies.

“So much of our decision making has been based on poor data and on our own experiences,” she said. “This is the first time that we have had real information to give our patients, and the information on [Depakote] is extremely concerning.”

Most Babies Are OK

Neurologist Gregory L. Barkley, MD, of Wayne State University, emphasized that most women taking anti-seizure drugs during pregnancy give birth to normal children. And he added that for many women the benefits of treatment clearly outweigh the risks.

“We don’t want women to abruptly stop taking these drugs,” he said.

Morrell said while Depakote may be the only appropriate treatment for some women, many others who are taking it for epilepsy, bipolar disorder, or migraine headaches may do just as well on another medication.

“Any woman taking [Depakote who might become pregnant] should talk to her physician about whether it is appropriate to continue,” she said.

By Salynn Boyles, reviewed by Charlotte E. Grayson, MD

SOURCES: News conference, American Epilepsy Society’s 58th Annual Meeting, New Orleans, Dec. 3-7, 2004. Gregory L. Barkley, MD, associate professor of neurology, Wayne State University; chairman, Professional Advisory Board, The Epilepsy Foundation. Lewis Holmes, MD, director, North American Antiepileptic Drug Pregnancy Registry. Kimford Meador, MD, Melvin Greer Professor of Neurology, University of Florida. Martha J. Morrell, MD, clinical professor of neurology, Stanford University, California.