There have been multiple recent reports indicating that the use of valproate during pregnancy may be associated with lower IQ, cognitive problems, and developmental delays in exposed children.  This has prompted the FDA to issue a warning regarding the use of valproate-containing drugs, including Depakote and Depakene, during pregnancy:

FDA is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant. Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from “D” (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to “X” (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).

Valproic acid is the first psychotropic medication to be labeled category X.  Interestingly, the category X label only applies to the treatment of migraines; the report states that treaters may consider the use of valproate-containing patients in certain women, including women with bipolar disorder and epilepsy.

RECOMMENDATION: Valproate products should not be used in pregnant women for prevention of migraine headaches and should be used in pregnant women with epilepsy or bipolar disorder only if other treatments have failed to provide adequate symptom control or are otherwise unacceptable.

In their report, the FDA also emphasized the importance of effective contraception in women taking valproic acid in order to reduce the risk of unplanned pregnancy.  There are certainly women with bipolar disorder who respond better to valproic acid than other mood stabilizers; however, given the significant risks associated with the use of valproic acid during pregnancy, many women taking valproic acid may want to consider other options for mood stabilization prior to conception.

Ruta Nonacs, MD PhD

Valproate Anti-Seizure Products: Drug Safety Communication – Contraindicated for Pregnant Women for Prevention of Migraine Headaches