July 21, 2008 -- The epilepsy and migraine prevention drug Topamax has been linked to an increased risk of birth defects in babies born to epilepsy patients who took it during pregnancy, a small study shows.
In a study published in the latest issue of the journal Neurology, taking Topamax (topiramate) during pregnancy was associated with a birth defect risk within the range of risk seen in other anti-epileptic drugs, researchers reported.
But the incidence of birth defects seen when Topamax was taken with other anti-epileptic drugs was higher than expected.
The study was small, but it is among the first to link Topamax to birth defects in humans, confirming what has been seen in previous animal studies.
"More research needs to be done to confirm these results, especially since it was a small study," researcher John Craig, MRCP, of the Royal Group of Hospitals in Belfast, Northern Ireland said in a news release.
He added that although the study included only epilepsy patients, the results may be of particular relevance for migraine patients "since [Topamax] is also used for preventing migraines, which is an even more common condition that also occurs frequently in women of childbearing age."
Topamax Is a Top Migraine Drug
In the four years since receiving FDA approval for the treatment of migraines, Topamax has become one of the most widely prescribed drugs for the condition, which affects almost 30 million Americans.
Women are three times more likely to suffer from migraines than men; women in their childbearing years are particularly vulnerable.
If the study findings are confirmed, they suggest that Topamax may not be an appropriate migraine treatment for women who are considering pregnancy, neurologist Shlomo Shinnar, MD, PhD, of New York's Montefiore Medical Center tells WebMD. Shinnar is a spokesman for the American Academy of Neurology.
"The tolerance for risk is different for epilepsy patients, because uncontrolled seizures are a clear risk to the fetus," he says. "Migraines can be quite debilitating for the mother, but they do not generally pose a risk to a fetus."
The study included 203 women with epilepsy who became pregnant while taking Topamax, either alone or in combination with other anti-epilepsy drugs.
Of the 178 live births that occurred, three babies whose mothers took Topamax alone and 13 whose mothers took Topamax along with other anti-epilepsy drugs had major birth defects.
Four of the babies had cleft palates or cleft lips, which was 11 times higher than would be expected among women not taking epilepsy medication. Four male babies had genital birth defects, with two of these classified as major birth defects.
The birth defect rate was highest among women who took Topamax in combination with the epilepsy drug valproate, which has been linked to birth defects in numerous studies and epilepsy databases.
NYU professor of neurology Jacqueline A. French, MD, tells WebMD that the birth defect rate among women taking Topamax alone was within the realm of what has been seen with epilepsy drugs considered safer than valproate. French is a spokeswoman for the American Academy of Neurology.
"It was somewhat surprising that the rate was so high when Topamax was used with valproate," she says. "But the risk associated with valproate is well known, and this drug is already avoided whenever possible during pregnancy."
French tells WebMD that the study was too small to accurately assess the risk to babies born to mothers who take Topamax alone.
Kara Russell, a spokeswoman for Topamax manufacturer Ortho McNeill Neurologics, expressed similar concerns. "The sample sizes in this study were small, so more work needs to be done to really understand the results," she tells WebMD.
"We continue to support studies to provide clarity on the use of our drug in this population," she adds. "But it is really hard to reach a conclusion based on the small sample sizes in this study."
Three major databases currently track birth defects among babies born to women taking epilepsy drugs, but only one has so far provided information on Topamax, French says.
"We should know more soon when the other databases report on this drug," she says.
Like Shinnar, French emphasizes that for pregnant women with epilepsy, uncontrolled seizures have proven to be a much greater risk to the fetus than any epilepsy drug, including valproate.
The American Academy of Neurology recommends that women with epilepsy considering pregnancy take only one drug, if possible, to control seizures and that they take epilepsy drugs in the lowest effective dosages.
But discontinuing treatment during pregnancy can be very dangerous for a patient and her baby, she adds. During a mother's seizure and for the immediate period following the seizure, the level of oxygen being delivered to the placenta and fetus is low. This effect causes a drop in the infant's heart rate -- a sign of fetal distress. There are addition concerns of fetal and placental injury during the mother seizure which can lead to an increased risk of miscarriage.
"It's a double whammy," French says. "The baby has already been exposed and with withdrawal there is the added risk that a woman will suffer a seizure."