Rx CARE

Newer antiepileptics may be better choice for women

Are women with epilepsy receiving adequate health care? A review of a new survey reported in the Journal of Women's Health and Gender-based Medicine revealed a low level of knowledge and high degree of uncertainty among healthcare professionals about best practices in caring for women with the disorder.

The more than one million American women and girls with epilepsy face a barrage of medical concerns, including reproductive problems, sexual dysfunction, excessive weight gain, and osteoporosis.

However, the survey of more than 3,500 health professionals conducted by the Epilepsy Foundation found that fewer than a third knew about menstrual cycle-related seizures, only 11% knew about epilepsy-related sexual dysfunction, and 73% could not identify which antiepilepsy drugs (AEDs) are known to interfere with oral contraceptives. Further complicating matters is the recent upsurge in utilizing AEDs to treat other conditions that affect an even greater number of women, such as migraines, pain, depression, and bipolar disease.

Speaking at a press briefing held by the Epilepsy Foundation in New York, Martha Morrell, M.D., director of the epilepsy center at Columbia University's medical school, questioned whether psychiatrists or other physicians prescribing these medications are counseling patients on their method of birth control because some of the older liver-enzyme-inducing AEDs (carbamazepine, phenytoin, primidone, phenobarbital) may result in a failure of hormonal contraception. Pharmacists should counsel women receiving AEDs on this possible interaction.

Studies have also shown a reduction in bone mineral density and impaired calcium metabolism during treatment with enzyme-inducing AEDs. Vitamin D and calcium supplementation are recommended for symptomatic and high-risk patients.

Over the past decade, there have been eight new drugs approved for the treatment of epilepsy, including gabapentin (Neurontin, Parke-Davis), lamotrigine (Lamictal, GlaxoSmithKline), topiramate (Topamax, Ortho-McNeil), and oxcarbazepine (Trileptal, Novartis).

"Many of the newer AEDs do not cause changes in hormones, do not seem to be associated with bone disease, do not seem to cause sexual dysfunction or polycystic ovary syndrome, and may be safer to use during pregnancy," remarked Morrell.

Specifically, gabapentin and lamotrigine have no effect on the cytochrome P-450 system and have not been reported to result in failure of hormonal contraception. However, many physicians may be unwilling to use new agents in monotherapy without supportive FDA labeling. Only two new agents—felbamate (Felbatol, Wallace) and oxcarbazepine—are approved for monotherapy, and lamotrigine received an indication for withdrawal to monotherapy in refractory patients.

Treatment with some of the older AEDs has also been shown to impair folate absorption. Folic acid supplementation, which helps prevent neural defects, is key for women with epilepsy. Yet, a recent study found that most of these women are not informed of this by their doctors.

In the 1998 guidelines issued by the American Academy of Neurology, single-drug therapy at the lowest possible dose is recommended for women with epilepsy of childbearing age who wish to become pregnant, unless seizure control requires more than one drug. More than 90% of these women who receive optimal care can expect good pregnancy outcomes.

The guidelines suggest that therapy be optimized before conception. Preferably, AED therapy changes should be completed at least six months before planned conception, and folic acid supplementation started with at least 0.4 mg per day. Additionally, the patient should be counseled on the importance of medication compliance and have AED-level monitoring done during the pregnancy.

Morrell also reported on a study that confirmed that taking two medications during pregnancy endangers the fetus more than taking just one and makes the new point that switching drugs during pregnancy is as dangerous as taking two drugs at once.

Another important consideration for women with epilepsy is the need to reassess their doses of AEDs once they experience menopause.

"Research now shows there is a relationship between estrogen levels and seizure activity," stated Morrell. Many women with epilepsy develop seizures around the time of puberty. One-third to one-half of women have hormonally sensitive seizures, which happen more during the premenstrual period, pregnancy, or perimenopause. When these women reach menopause, the decision to place them on hormone therapy requires careful consideration of the risks versus benefits and close monitoring.

Treating women with epilepsy poses many challenges, but Morrell emphasized the importance of selecting an AED that preserves reproductive and bone health. "With the right information, women with epilepsy and [their healthcare team] can manage some of these problems by adjusting treatment or trying different medications altogether," she said.

Tammy Chernin, R.Ph.

Tammy Chernin. Newer antiepileptics may be better choice for women.

Drug Topics

2001;15:16.