Valproate Teratogenicity: A Moving Target

Within several years after receiving U.S. Food and Drug Administration (FDA) approval in the late 1970s, valproate was shown to increase the risk for major congenital malformations and learning disabilities in the offspring of women who used the drug during pregnancy. Nonetheless, its use in pregnant women has persisted for more than four decades, recently resulting in numerous lawsuits and, in countries other than the United States, criminal indictments of the manufacturers of valproate. The use of valproate in pregnancy persisted and extended beyond its original indication for the treatment of epilepsy. Several recent studies indicate that the drug is more often prescribed to treat pregnant women with bipolar depression and migraine than for seizure control. Especially concerning is the absence of valproate from the list of more than 60 drugs for which the FDA has implemented Risk Evaluation and Mitigation Strategies to prevent or limit untoward consequences associated with specific drugs. Until this step is taken, avoidance of the teratogenic effects of valproate will rely on the vigilance of those caring for women and people with the potential to get pregnant.