Study finds more risks to unborn in epilepsy drug
One in four women who took the widely used epilepsy drug valproate while pregnant gave birth to children who were mentally retarded, double the rate among women who took other epilepsy medicines, researchers said Thursday.
The report, presented at the annual meeting of the American Academy of Neurology in Boston, was the latest to document the potential dangers of valproate to the unborn.
Last summer, researchers reported that 1 in 5 women who took the drug, sold as Depakote by Abbott Laboratories, had pregnancies that resulted in fetal death or birth defects, including malformed hearts and genitals, cleft palates and artery deformities.
Dr. Jacqueline French, a professor of neurology at the University of Pennsylvania, who was not involved in the study, said the latest findings were of great concern and that women of childbearing age should be informed of the risks, which are not included on the drug’s warning label.
“It is time to have a different kind of conversation with our patients,” French said.
An estimated 2.7 million Americans have epilepsy, a disorder in which clusters of nerve cells in the brain signal abnormally, causing seizures. Valproate has long been the preferred drug for treating generalized epilepsy, which affects up to one-half of patients.
The drug is also used to treat migraine headaches and some psychiatric conditions, including bipolar disorder. Abbott reported Depakote sales of $1.2 billion last year in the United States.
The latest study, led by Dr. Kimford J. Meador of the University of Florida in Gainesville, compared the IQs of 185 2-year-olds whose mothers had taken one of four epilepsy drugs while pregnant.
In addition to valproate, the drugs were carbamazepine, sold as Tegretol, lamotrigine (Lamictal) and phenytoin (Dilantin).
IQs were determined using the Bayley Scale for infant and toddler development. Researchers said a score of 100 was average and below 70 was mentally impaired.
Children whose mothers had taken valproate had an average IQ of 81, compared to an average of 96 for children in the carbamazepine group, 94 for the lamotrigine group and 95 for the phenytoin group.
Twenty-four percent of children whose mothers took valproate had IQs below 70, compared to 13% for carbamazepine, 11% for lamotrigine and 12% for phenytoin.
In the general population, an average of 2% of children have IQs below 70.
Meador said the research, funded by the National Institutes of Health, did not support a conclusion that all four drugs might cause mental retardation because the study was small and lacked a control group.
“The big thing is the difference between valproate and the other drugs,” he said.
Abbott said in a statement that all epilepsy drugs posed serious risks, and Depakote’s label made clear that the drug should not be a first-choice treatment for women of childbearing age.
Abbott said it was important to follow the progress of children in the study to see if they displayed cognitive impairments at age 6, when the study was scheduled to end.
The Food and Drug Administration had no comment on the study.
Women who must rely on valproate because they don’t respond to other drugs should take the lowest possible dose if they become pregnant, Meador said. He stressed that pregnant women should not stop their epilepsy medication because a seizure could be dangerous for them and their fetuses.
French called for a mandatory informed consent process in which women of childbearing age would have to sign a document saying they were informed of the dangers before receiving prescriptions for valproate.