The drug Depakote, while useful as a treatment for epilepsy and other conditions, has a dangerous tendency to cause debilitating birth defects.

What is Depakote?

Depakote
is also known by the name of its active ingredient valproic acid, or valproate. The same ingredient is sold under the trade names Depakene and Stavzor. It’s not known exactly how Depakote works, but scientists believe its mechanism may have to do with an increase in concentration of the neurotransmitter gamma-aminobutyric acid, or GABA.

First approved by the FDA in March 1983, Depakote is now approved as a treatment for epilepsy and the manic episodes associated with bipolar disorder. The FDA also approved it later for the prevention of migraines. It is currently manufactured by AbbVie, a division of Abbott Laboratories.

Depakote and Birth Defects

Studies show that children of mothers who took Depakote while pregnant are up to four times more likely to have major congenital defects than children of mothers who used other comparable medications.

The North American Antiepileptic Drug Pregnancy Registry reports that major malformations occur at a rate of 9 to 11 percent in the children of mothers who took valproate during pregnancy at an average dose of 1,000 milligrams per day.

The congenital defects most strongly associated with Depakote are neural tube defects, which are malformations of the brain, spine, or spinal cord. The two most common such defects are spina bifida, in which the spinal column does not completely close, and anencephaly, which is a failure of the brain and skull to develop. Children exposed to valproate in utero are estimated to have a risk of spina bifida of 1 to 2 percent, compared to 0.06 to 0.07 percent in the general population.

Other Depakote birth defects may include:

• Cardiovascular malformations
• Cleft lip and cleft palate
• Craniosynostosis (where the bones of the skull fuse prematurely, causing malformation of the head and preventing proper growth of the brain)
• Hypospadias (a condition in boys in which the urethra opens on the underside of the penis instead of at the end)
• Limb malformations such as club foot and supernumerary digits

Studies also show that some children exposed to valproate in-utero end up with lower IQ scores than children exposed to other antiepileptic drugs. Another study shows that fetal exposure to valporate may increase the risk of developing autism spectrum disorders. The observational study found that autism and related disorders occurred almost three times as often in children exposed to valproate in utero.

FDA Depakote Warnings

Because the risks of Depakote birth defects is so severe, it is not indicated for women of childbearing potential unless it is essential for managing their medical condition.

As a treatment for migraine, Depakote is in FDA pregnancy category X, meaning that there is positive evidence of human fetal risk when an expecting mother takes this drug during pregnancy, and the risk is great enough that it clearly outweighs the potential benefits.

For treating the more serious conditions of epilepsy and manic episodes of bipolar disorder, the FDA places Depakote in pregnancy category D, meaning the benefits may warrant use of the drug in pregnant women despite the risks.