The US Food and Drug Administration (FDA) has announced that the children of mothers who took medications including or related to valproate(Drug information on valproate) sodium during pregnancy show decreased IQ scores, and that these drugs are now contraindicated for pregnant women.
Contraindicated valproate products include valproate sodium (Depacon), divalproex sodium(Drug information on divalproex sodium) (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics.
While valproate-containing medicines already have a boxed warning for fetal risk, the FDA’s strengthened recommendations are based on the results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, which showed that children exposed to valproate products in utero had decreased IQ at age 6 when compared to children who were exposed to other antiepileptic drugs. The IQ difference varied between 8 and 11 points.
Valproate products have several FDA-approved uses, including the prevention of migraine headaches, treatment of epilepsy seizures, and treatment of manic episodes associated with bipolar disorder (manic-depressive disorder). For bipolar disorder and seizures valproate may have value in pregnant women, but it should only be taken if other medications have not controlled the symptoms or are otherwise unacceptable.
“Valproate medications should never be used in pregnant women for the prevention of migraine headaches because we have even more data now that show the risks to the children outweigh any treatment benefits for this use,” said Russell Katz, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.
The FDA is working with manufacturers to make changes to the drug labels to reflect the new information and change the pregnancy category for prevention of migraine headaches to category X (the drug’s risks outweigh the drug’s benefits for this use) from category D (the drug’s benefits outweigh the drug’s risks for this use). Valproate products will remain category D for the other two approved indications—epilepsy and manic episodes associated with bipolar disorder.