Commonly Prescribed Medications Linked to Birth Defects

By Ann Scherer
Special to EpilepsyUSA
Posted: October 24, 2005

Millions of American women use anticonvulsant drugs to treat a variety of chronic health problems, including epilepsy, migraine, nerve pain, and mood disorders. Recent research on the long term effects of some anticonvulsants on women's health and during pregnancy has sparked a national educational campaign to alert healthcare providers to the new information and encourage women to be more involved in decisions about their health care.

Sometimes, pregnancy is the starting point. When 23-year-old Liz Wood, of Calera, AL, became pregnant with her son, she knew her life would change. As a single mom-to-be, she knew she'd face special challenges. What she didn't expect was an entirely new medical diagnosis.

During the ninth month of her pregnancy, Liz experienced a seizure, a grand mal convulsion that stopped her breathing. "I almost died, and I almost lost the baby," she recalled.

After both survived delivery, the doctors sent them home. The seizures, they assured her, would more than likely stop. But they didn't stop, and after months of tests to find the cause, Liz got her diagnosis: temporal lobe epilepsy, a neurological condition that requires long term use of seizure-preventing (anticonvulsant) medication.

Epilepsy can begin at any age and, in many cases, no single cause can be found. While equal numbers of men and women develop this neurological condition, its unique effects on women and its links to female hormones are only now being recognized.

Research shows that many women are more likely to experience seizures (and even the onset of epilepsy itself) at puberty, at specific points of the menstrual cycle, at menopause and, as Liz discovered, during pregnancy.

"Thirty percent of women with epilepsy have seizures around their periods," said Cynthia L. Harden, M.D., associate professor of neurology and neuroscience at Cornell University, who has studied the phenomenon. "They may occur right before the period or at ovulation, two weeks earlier. Hormonal changes influence the timing of the seizures, but do not cause epilepsy."

For Liz, however, the question of what led her to have seizures was of less immediate importance than the need to stop them. And that, she learned, meant long term treatment with one of the more than 20 anticonvulsant drugs, some newly approved by the U.S. Food and Drug Administration, others in use for more than 50 years.

Three Million Women

Until recently, most anticonvulsants were used primarily to treat the more than two and a half million Americans with epilepsy, including one million women. Now as many as two million other women may be taking them to treat such conditions as mood disorders, nerve pain and migraine.

"Anticonvulsants are used by a large number of women of childbearing age who do not have epilepsy and many are not aware of the side effects of these drugs on themselves or their offspring," says Gregory L. Barkley, M.D., who chairs the professional advisory board of the Epilepsy Foundation. "The best use of any medicine is to know its effects."

New research is showing that those effects may have both short term and long term consequences for women. While not all women who use the drugs are affected, and not all drugs carry the same risk, the cumulative list is a formidable one: weight gain, thinning bones, mood changes, bad skin, less hair on the head, more hair on the face, irregular periods, difficulty in conceiving, higher levels of male hormones, a more masculine appearance, and reduction in the effectiveness of hormone-based birth control.

Risks during Pregnancy

Potential effects on children whose mothers take anticonvulsants during pregnancy are even more troubling – and that's of continuing concern to 29-year-old Julie Thomas, of Laurenceville, Ga.

Now pregnant with her first child, Julie has had seizures since childhood and has taken anticonvulsants for years. She hopes for the best, but is concerned about what effects the medication may be having. "I do worry constantly about it," she said, "even though my pregnancy has gone a lot smoother than I thought."

For the most part, the odds are comforting. Most babies born to women taking anticonvulsant drugs are born normal and healthy. However, rates of major malformations affecting the heart, skeletal or nervous system in children born to women on anticonvulsants are at least double the rate in the general population, occurring in 4–6 per hundred births vs the 2-3 per hundred births risk that all pregnant women face.

Those are average figures. What is harder to determine is how much risk individual drugs pose. Is drug A safer than drug B? Or would drug C be a better choice? Until recently, it was hard to say, and therapy was selected solely on the basis of potential to control a medical problem. Now new results from pregnancy registries, which track the effects of individual drugs on the developing child, are beginning to pinpoint some of the differences among the wide array of treatment options.

The North American Pregnancy Registry, based at Massachusetts General Hospital, has reported higher rates of fetal malformations among women taking phenobarbital or valproate (Depakene/Depakote) during pregnancy. Both drugs have a long history of effectiveness and are widely used. Reports from international registries and research groups have shown similar results in pregnancy, though based on fewer patients. Early research is also pointing to lowered childhood IQ and other developmental problems when these anticonvulsants are taken during pregnancy.

For many of the newer drugs, approved within the last 15 years, the level of risk is still unknown, although researchers expect it to be lower because some of the new drugs differ from the older, pre-1990 drugs in the way they affect the body's metabolism. That is somewhat reassuring for Julie Thomas, who's taking oxcarbazepine (trade name: Trileptal), approved within the last five years.

So far, however, the only major research study of a newer drug during pregnancy was reported earlier this year by the International Lamotrigine Pregnancy Registry in the U.K. The registry is supported by GlaxoSmithKline, which manufactures the drug under the trade name Lamictal. Based on its results, the registry reports that the risk of birth defects in women taking Lamictal during pregnancy is about the same as the normal risk in the population. The Epilepsy Foundation is calling for more research on this and on all the anticonvulsant drugs approved in the last 15 years, however.

Birth of a Campaign

Last year, the Epilepsy Foundation, concerned about emerging information on the effects of anticonvulsants on women's lives, convened an international forum of experts in New York to encourage further research and the sharing of information by pregnancy registries around the world. Earlier this year, the Foundation organized a follow up forum, joined by representatives of a variety of groups concerned with women's health and medical research. As a result of those deliberations, the Foundation has launched Anticonvulsants & Women: A Call to Action, a major educational campaign targeted to women and the health care community.

"We want women to be more informed about the medicines they're taking and to have a better sense of what the risks and benefits really are," said Debbie Carr, the Epilepsy Foundation's vice president for quality of life and research.

"We want women to talk with their healthcare providers about the various options among anticonvulsants. Some women may only be able to get seizure control or medical relief with a drug that carries a higher risk, and that may still be the best choice, given that seizures during pregnancy are also damaging to the baby. The key is to have the information and to make an informed choice," she said.

"We also want to encourage pregnant women who are taking anticonvulsants for any reason to sign up with the North American Pregnancy Registry. That's where the new information about the safest drugs will come from. It's absolutely vital to get more women signed up."

Value of Pregnancy Registries

Pregnancy registries enroll women who are taking specific medicines early in their pregnancy. The registries then receive confidential reports on infant health or problems from the women's physicians after the babies are born. In this way, anticonvulsants that are the safest (or riskiest) in pregnancy can be identified. Julie Thomas is looking forward to the time when women like herself will have that kind of information about each of the anticonvulsants that they may need to take during pregnancy. "It would be wonderful," she says.

"Currently we have 4,600 women on the registry and about 60 women are enrolled every month." said Lewis B. Holmes, M.D., professor of pediatrics at Harvard, who runs the North American Pregnancy Registry. "But we have to do a better job of getting the word out."

Given so many concerns, however, and the fact that 50 percent of all pregnancies are unplanned, should women on anticonvulsants stop taking the meds when they learn they are pregnant? The answer, from all the experts, is a resounding "No!"

"Suddenly stopping an anticonvulsant risks severe rebound seizures or return of the condition for which the medication has been prescribed," said Dr. Barkley.

Instead, women should contact their health care providers who will, in most cases, urge continuation of the treatment, with careful monitoring. In general, use of a single anticonvulsant at the lowest effective dose, combined with use of folic acid and other vitamin supplementation, is considered safest.

The Foundation's Anticonvulsants & Women: A Call to Action campaign also urges women to meet with their healthcare team and discuss any medicine changes before the pregnancy begins. They are also being advised to explore ways of preventing other negative effects on quality of life (like thinning bones, mood disturbances, or unwelcome changes in weight.

Women may keep current on emerging research in this area through the Epilepsy Foundation's website and, if they become pregnant, register with the North American Pregnancy Registry online or by calling (888) 233-2334.

Looking Ahead

Liz Wood is now 28 and her son is a sturdy 5-year-old. Newly graduated from the University of Montevallo with a degree in mass communications, Liz would like to have another baby some time in the future. She is one of the millions of women who stand to benefit as research yields new information on the relative safety of anticonvulsant drugs.

"I know it would be a high risk pregnancy," she said. "But I would seek out a lot of information. I have already been given names of specialists in pre-conception planning if I ever do make the decision."

In the meantime, she volunteers with the Epilepsy Foundation of North and Central Alabama, and counsels other women. "I say, you have to find out the most you can. Go to the Epilepsy Foundation and get the best doctor you can find."

For more information about the Anticonvulsants & Women: A Call to Action campaign, contact (800) 332-1000 or visit the Epilepsy Foundation's online Call to Action section.