SUNDAY, June 5, 2011 (HealthDay News) -- Four of the most frequently prescribed epilepsy drugs appear to increase the risk of serious birth defects when taken early in pregnancy, a new study finds.
And the higher the dosage, the greater the risk, the international team of researchers reported in the June 6 online edition of The Lancet Neurology.
"Our results show that dose selection is as crucial as the choice of drug," the authors said in a journal news release. Their study gives doctors the opportunity to prescribe the safest anti-seizure medication at the safest level for women with epilepsy who want to get pregnant, they said.
The drugs studied were carbamazepine (Tegretol, Epitol), lamotrigine (Lamictal), valproic acid (Depakote), and phenobarbital.
The rate of birth defects was higher with increased dose for all the drugs, the researchers said, but they emphasized that the vast majority of women in their study delivered healthy children.
Most women with epilepsy need to take anti-seizure medication or risk harming themselves or their baby. Previous studies found that valproic acid, in particular, might increase the risk of birth defects, but those studies didn't look at individual doses. Nor did they take into account other influential factors, such as family history of birth defects or severity of epilepsy.
"Present guidelines caution on the use of valproic acid during pregnancy, but offer little guidance on alternative options and how to manage women whose seizures cannot be controlled by other drugs," Dr. Torbjorn Tomson, of the Karolinska Institute in Stockholm, Sweden, and colleagues, said in the news release.
For their 11-year study, the researchers used data from the International Registry of Antiepileptic Drugs and Pregnancy on nearly 4,000 pregnancies in 33 countries.
In all, 230 pregnancies resulted in major birth defects by the end of the first year after birth.
Low doses of lamotrigine (less than 300 milligrams [mg] per day) and carbamazepine (less than 400 mg per day) carried the smallest risk, the investigators found.
The greatest risk to the fetus was seen with the highest doses of valproic acid (1,500 mg a day or more) and phenobarbital (150 mg or more a day), the researchers said.
A family history of major birth defects quadrupled the risk, they found.
"The findings are important to the clinician treating people with epilepsy because they provide specific information not only on the drug but also on the dose," Dr. W. Allen Hauser, a professor of neurology and epidemiology at Columbia University in New York City, said in an accompanying editorial.
"It is easy to recommend against use of a specific drug (valproic acid, for instance) because of a higher risk of malformations, but if seizure control is not possible with alternative therapeutic regimens, such recommendations are difficult to implement," he continued.
"Incidence of major congenital malformations associated with a low dose of a higher-risk drug might be lower than that associated with a high dose of a lower-risk drug," Hauser added.
Commenting on the study, Dr. Jennifer Wu, an obstetrician/gynecologist with Lenox Hill Hospital in New York City, said: "This new study gives doctors and epileptic patients more information about safer drug choices. Patients with epilepsy should always try to plan their pregnancies. Some patients will be able to come off their medications, some patients will lower their dosages, and some patients will switch medications. This should all be done in the non-pregnant state."
For more about epilepsy, visit the U.S. National Library of Medicine.