Panel: Avoid Epilepsy Drug in Pregnancy

New Guidelines Urge Pregnant Women to Avoid Taking Valproate Because of Risk of Birth Defects

From the WebMD Archives

April 27, 2009 (Seattle) -- Women with epilepsy should avoid taking the drug valproate (Depakote) during pregnancy if possible, according to new guidelines developed by the American Academy of Neurology (AAN) and the American Epilepsy Society.

"There is good evidence that valproate, whether used by itself or in combination with other medications, increases the risk of major birth defects, including cleft palate and spinal bifida," says guideline co-author Gary S. Gronseth, MD, vice chairman of neurology at the University of Kansas Medical Center in Kansas City.

Additionally, taking valproate during pregnancy has been linked to lower IQs in children, he tells WebMD.

The guidelines come on the heels of a study showing that women with epilepsy who took valproate during pregnancy gave birth to children whose IQ at age 3 averaged up to 9 points lower than the scores of children exposed to other epilepsy drugs.

In response to the guidelines, a spokesperson for Abbott, which makes valproate, said the drug may be the only effective medication for some women, but doctors and patients should discuss risks and benefits of treatment.

Pregnant women may also want to avoid taking the seizure drugs phenytoin (Dilantin) and phenobarbital, as they too have been linked to lower IQs in children, Gronseth says.

Epilepsy and Pregnancy

Gronseth and other panel members stress that pregnancy is safe for most women with epilepsy.

"Overall, what we found was very reassuring to woman with epilepsy planning to become pregnant," says lead guideline author Cynthia Harden, MD, director of the epilepsy division at the University of Miami's Miller School of Medicine.

"Contrary to previous dogma, women with epilepsy are not at a substantially increased risk of having a cesarean section, late pregnancy bleeding, or premature contractions or premature labor and delivery," she says.

Also, if a woman is seizure-free for nine months to one year before she becomes pregnant, it's likely that she will not have any seizures during the pregnancy -- even if she switches medications, Harden tells WebMD.

About 500,000 women of childbearing age in the U.S. have some form of epilepsy, which is characterized by brief disturbances of electrical activity in the brain, according to Harden. Three to five out of every 1,000 births are to women with epilepsy.


The guidelines were prompted by a thorough review of more than 50 articles published over the last 10 years. They were presented here at the AAN's annual meeting and simultaneously published online in the journal Neurology.

Other recommendations include:

  • If possible, women with epilepsy should avoid taking more than one epilepsy drug at a time during pregnancy, as doing so raises the risk of birth defects compared with taking only one medication.
  • Pregnant women with epilepsy should have their blood tested regularly. "Pregnancy has been shown to lower the levels of anti-epileptic drugs in the blood, which may put women at risk of seizures. Checking these levels and adjusting the medication doses should help to keep the pregnant woman seizure-free," Harden says.
  • Women planning to become pregnant should take at least 400 micrograms of folic acid a day, as supplementation has been shown to be "possibly effective" in preventing major birth defects. That's the same amount of folic acid already recommended by the CDC to prevent neural tube defects, especially spina bifida.
  • Smoking during pregnancy may increase substantially the risk of premature contractions and premature labor and delivery during pregnancy.

Epilepsy Drugs and Breastfeeding

The epilepsy drugs primidone (Mysoline) and levetiracetam (Keppra) were detected in breast milk at various levels "that may be clinically important," while valproate, phenobarbital, phenytoin, and carbamazepine (Tegretol) were not, the panel says.

"We didn't find much evidence one way or another that any of the drugs caused adverse effects in babies who were breastfed, but this information can help women and their doctors to make decisions about breastfeeding," Harden says.

Women should not stop taking any drug without consulting their physician, Harden stresses.

She suggests that women with epilepsy have a discussion with their doctor about seizure medications at least six months before becoming pregnant.

Valproate is an "excellent drug," and for some women, it may be the only medication that effectively controls their seizures, Gronseth says. "Women and their doctors have to weigh the potential risk of birth defects against the potential risk of uncontrolled seizures."


Valproate Also Used to Treat Migraines

"Luckily, it's not that hard to avoid valproate during pregnancy," as there are now more than a dozen seizure drugs available, says AAN spokesman Joseph Sirven, MD, professor of neurology at the Mayo Clinic in Phoenix.

Sirven points out that many more people, including pregnant women, take valproate to relieve migraine headaches.

"Lower doses are used than for epilepsy, so the drug may not pose the same problems [as when used to treat seizures]," he tells WebMD.

Nonetheless, women who have been prescribed valproate for any reason "should have a frank discussion with their doctors if they are planning to become pregnant," Sirven says.

WebMD Health News Reviewed by Louise Chang, MD on April 27, 2009



American Academy of Neurology 61st Annual Meeting, Seattle, April 25-May 1, 2009.

Cynthia Harden, MD, director, epilepsy division, University of Miami's Miller School of Medicine.

Gary S. Gronseth, MD, vice chairman of neurology, University of Kansas Medical Center, Kansas City.

Joseph Sirven, MD, spokesman; American Academy of Neurology; professor of neurology, Mayo Clinic, Phoenix.

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