Understand the needs of women with epilepsy, or risk OC failure

Increasing estrogen dose can compensate for effect of anti-epileptic drugs

Most providers are unaware of potential interactions between common anti-epileptic drugs and oral contraceptives (OCs) that can lead to OC failure, according to a national survey.1 This problem can be addressed easily: Increasing the estrogen dosage of OCs can compensate for the clearance caused by those anti-epileptic drugs that affect the hepatic cytochrome P450 (cyP450) enzyme system. However, many providers do not follow this guideline. Less than half of the physicians responding to the survey reported adjusting their patients' OC prescriptions. Some providers even said they reduced the estrogen dosage, which can only increase the risk of contraceptive failure.

While 91% of the physicians said they treated women with epilepsy of childbearing age, only 4% of the neurologists and none of the obstetricians knew the interaction between the most common anti-epileptic drugs and OCs. However, 27% of the neurologists and 21% of the obstetricians reported OC failures in their patients taking anti-epileptic drugs.

The issues of seizure control and birth control often can place women with epilepsy in a revolving door between family planners and neurologists in an effort to achieve contraceptive efficacy while continuing use of anti-epileptic drugs. A united effort is under way to stop the spinning through clear communication among providers, says Georgia Montouris, MD, medical director of the EPI-CARE Center at the Semmes-Murphey Clinic in Memphis and clinical associate professor of neurology at the University of Tennessee. This cooperation is key in treating the estimated 700,000 to 1.2 million U.S. women of childbearing age with epilepsy.

Providers are gaining a better understanding of women with seizure disorders through the Women and Epilepsy Initiative, says Mark Yerby, MD, MPH, associate clinical professor of neurology, public health, preventive medicine, and OB/GYN at Oregon Health Sciences University in Portland. The initiative, sponsored by the Epilepsy Founda tion of America, a nonprofit national organization in Landover, MD, is developing educational material to raise awareness of epilepsy's effects.

Hormones and epilepsy

It is important to understand how hormones influence seizure disorders, says Montouris. For a woman with epilepsy, this influence begins at puberty, with the onset of menarche having a significant bearing on seizure frequency.

An estimated 10% to 75% of women with epilepsy have catamenial epilepsy, categorized by seizure activity only at the time of menses. Partial seizures may increase during the two weeks from ovulation to menses, the follicular phase, while absence seizures may intensify during the luteal phase, from menses to ovulation. Menopause brings on more hormone fluctuations, which may trigger changes in seizure activity. For women who started their periods later in life and have easily-controlled catamenial epilepsy, menopause may result in less seizure activity, Montouris says.

"Interestingly enough, there are two peak times for the onset of epilepsy," she notes. "The first peak time is under age 10, and the second is over age 60, so in essence you are going to have patients who are going to be post-menopausal who conceivably can develop epilepsy for the first time."

Providers need to understand how anti-epileptic drugs impact the efficacy of hormonal contraceptives in prescribing birth control for their patients. These drugs increase the breakdown of contraceptive hormones in the body due to their effect on the cyP450: carbamazepine (Tegretol, Novartis Pharmaceutical Corporation, East Hanover, NJ ), phenobarbital (Donnatal, Robins Co., Richmond, VA ), phenytoin (Dilantin, Parke-Davis, East Hanover, NJ ), primidone (Mysoline, Wyeth-Ayerst, Philadelphia), and topiramate (Topamax, Ortho-McNeil, Raritan, NJ ).

Two recent drugs, gabapentin (Neurontin, Parke-Davis, Morris Plains, NJ ) and lamotrigine (Lamictal, Glaxo Wellcome, Research Triangle Park, NC), have no effect on this enzyme system and do not interfere with hormonal contraceptive effectiveness. Valproate (Depakote, Abbott Laboratories, North Chicago, IL) and felbamate (Felbatol, Carter Laboratories, Cranbury, NJ ) do not increase breakdown of hormones and may even increase hormone levels, which may require an adjustment in the contraceptive dose.

Women with epilepsy who use cyP450-inducing drugs may need to use oral contraceptives with higher levels of estrogen to overcome the increased clearance, Yerby says. A pill with 50 mcg of estrogen may be a suitable choice. Low-dose pills and the mini-pill are not effective choices for those women taking the cyP450 anti-epileptic drugs. These same cyP450 drugs also may cause problems for women with Norplant levonorgestrel implants. Backup methods of contraception such as condoms or foam are encouraged to protect against unplanned pregnancy.

Women with epilepsy who receive depomedro- xyprogesterone (DMPA) injections may need to have their injections given more frequently due to the effects of cyP450 anti-epileptic drugs. Some providers are now using DMPA for control of true catamenial epilepsy, Montouris says.

There is no "best" medication, says Yerby, so go for the one that gives the best control. Women with epilepsy, especially those who are hormonally sensitive, may fear their chosen birth control method will worsen their seizures, he says. Help them understand this generally is not the case.

OCs are a very effective method of birth control for women with epilepsy, stresses Aashit Shah, MD, assistant professor and residency coordinator in the department of neurology at Wayne State University in Detroit. Even with the need for balance among some of the anti-epileptic drugs, OCs still offer effective contraception, Shah says.

"There is no contraindication to the use of birth control pills, and I say that because that there are a lot of people who still believe you can't take them because they think they will make your seizures worse," Montouris agrees. "It will not affect the seizures. It just might compromise the efficacy of the contraceptive."

Family planners who provide prenatal care should help patients with epilepsy understand the condition is not a contraindication to pregnancy. Well over 90% of epileptic women on medication will have a normal pregnancy outcome, she says. Women of childbearing age should take folic acid daily as a neural tube protectant, especially if they are on drugs known to have an increased risk of neural tube defects, such as carbamazepine and valproic acid, she notes.

Women with epilepsy may have some difficulty in becoming pregnant, she observes. Higher rates of infertility are seen in this population, as compared with the general population, she says. Anovulatory cycles are common, and polycystic ovary disease also is noted in this population.

The national average for congenital malformations is 2% to 3%, but for women on anti-epileptic drugs, it is 4% to 6%, she says. To assess the drugs' effect on pregnancy, the first North American registry for pregnant women on anti-epileptic drugs has been established at Massachu setts General Hospital in Boston. Participants will be given educational materials on preconception planning and prenatal care. Findings will be analyzed to assess the fetal risk from all anti-epileptic drugs in pregnancy. Montouris is directing a similar registry sponsored by Parke-Davis for those who use Neurontin. (See box at left for registry phone numbers.)

"It is important that we know the effects of these newer drugs on the outcome of pregnancy," she says. "Animal studies say that they are safe, but we don't know anything else."


1. Krauss GL, Brandt J, Campbell M, et al. Antiepileptic medication and oral contraceptive interactions: a national survey of neurologists and obstetricians. Neurology 1996; 46:1,534-1,539.