Study Ties Epilepsy Drug to Fetal Risk

One in five women who took the widely used epilepsy drug valproate in a clinical trial had pregnancies resulting in birth defects or fetal death, researchers said Monday.

The drug, sold as Depakote by Abbott Laboratories Inc., was substantially riskier to unborn children than three competing medicines examined in the study. The researchers found cases of malformed hearts and genitals, cleft palate and artery deformities among children born to women taking the drug.

The report in the journal Neurology was the latest to document the potential dangers of valproate to fetuses. The drug is also used to treat headaches and some psychiatric conditions, including bipolar disorder.

Dr. Brien J. Smith, a neurologist at Henry Ford Hospital in Detroit, said that the study was convincing and that doctors should now avoid prescribing valproate for women of childbearing age.

Epilepsy is a disorder in which clusters of nerve cells in the brain signal abnormally, causing seizures. An estimated 2.7 million Americans are affected. Valproate has long been the preferred drug for treating generalized epilepsy, a form that affects half of patients.

The researchers, led by Dr. Kimford J. Meador of the University of Florida in Gainesville studied 333 pregnant women at 25 centers in the U.S. and England.

The women had been taking one of four drugs -- valproate, carbamazepine, phenytoin or lamotrigine -- when they became pregnant and continued use during their pregnancy.

Twenty percent, or 14, of the 69 women on valproate had pregnancies that resulted in fetal deaths or birth defects.

For phenytoin, which is sold as Dilantin, six of 56 women, or 11%, had pregnancies ending in fetal death or congenital malformations.

Nine of the 110 women who took carbamazepine (Tegretol), or 8%, had pregnancies that ended in fetal death or birth defects. The rate for lamotrigine (Lamictal), was 1% -- one of 98 women on the drug.

Meador said the results showed that valproate should not be the drug of first choice for women of childbearing age.

But he added that it was less clear what the alternative should be.

He was reluctant to declare Lamictal the safest drug of the four because other studies had found a higher rate of birth defects associated with its use.

He also said pregnant patients should continue to take their epilepsy medicine because seizures could be dangerous for them and their unborn children.

Women of childbearing age who must take valproate -- because they don’t respond to other drugs, for example -- should take the lowest dosage possible, Meador said.

Researchers will monitor the children of the women in the study for six years to see whether they have cognitive problems related to the drugs, he said.