Depakote Birth Defect Risk Highlighted in New Study

The side effects of Depakote, a popular anti-seizure medication, and other valproate-based drugs could be linked to a number of major birth defects when used by pregnant women, according to the findings of a new study. 

European researchers published the results of a new study on the Depakote birth defect risk in the most recent issue of the New England Journal of Medicine. The researchers found that using Depakote increased the risk of six major types of birth malformation, including spina bifida, cleft palate, abnormal skull development, malformed limbs, holes in the heart, and problems with the urinary tract.

Depakote (dilvalproex) and other valproate-based anti-seizure medications, usually used to treat epilepsy, have long been associated with birth defects. Late last year the FDA added more stringent warnings about birth defects to Depakote and other drugs in the same class, which also includes Depacon, Depakine and Stavzor.

The latest study helped to quantify risks based on different types of birth defects from Depakote. Researchers looked at data collected from eight published cohort studies where women were exposed to valproic acid during their first trimester. Their results indicated that exposure to Depakote during early pregnancy could cause significant increased risk of a variety of birth defects. They found that taking the epilepsy drug resulted in a 12-fold increased risk of spina bifida, and a 7-fold increased risk of craniosynostosis (abnormal skull). There was also a five-fold increased risk of cleft palate, and 2.5 times the risk of atrial septal defect (a hole in the heart).

Earlier data gleaned by FDA from the North American Antiepileptic Drug (NAAED) Pregnancy Registry found that the use of valproate during pregnancy increases the risk of major birth defects and malformations. In particular, the risk of giving birth to a child with a neural tube defect was 1-in-20 for women who took valproate during the first 12 weeks of pregnancy. The risk for mothers not taking valproate was 1 in 1500 in the U.S.

The NAAED Registry reported that more than 10% of women who took an average of 1,000 mg per day of Depakene or Stavzor during pregnancy gave birth to children with some kind of major malformation. Other birth defects whose risks are increased include craniofacial defects, cardiovascular malformations and malformations of other body systems.

Pregnancy problems with Depakote have been long recognized. A “black box” warning has been on the medication’s label since 2006, warning about potential Depakote birth defects associated with use of the drug during pregnancy. A study done that year found that about 20% of babies born to mothers taking Depakote suffered serious problems, as opposed to other drugs which only had rates of between 1% and 10.7.

Researchers in the most recent study concluded that use of Depakote and similar antiepilepsy drugs significantly increased the risks of specific birth defects during the first trimester, meaning that the damage could be done before a woman is aware she is even pregnant.

Abbott Laboratories, the creator of Depakote, is currently being probed by the U.S. Department of Justice (DOJ) over its sales and marketing of the drug. Federal investigators are looking into whether the company violated Medicare or Medicaid reimbursement laws. Depakote was first approved by FDA in 1983. Depakene, the first drug of the class, was approved in 1978.