Depakote

The Lanier Law Firm Investigating Depakote Cases

Depakote (divalproex sodium), manufactured by Abbott Laboratories, was first approved by the Food & Drug Administration (FDA) in 1978 for the treatment of epilepsy. Divalproex sodium is a compound that contains sodium valproate and valproic acid. More recently, the drug has been approved for the treatment of  seizure disorders, certain psychiatric conditions (manic phase of bipolar disorder), and to prevent migraine headaches. The drug works by restoring the balance of certain natural substances (neurotransmitters) in the brain. 

Depakote risks for pregnant women and fetus health

The drug Depakote is manufactured by Abbott Laboratories and previously was prescribed to pregnant women without label warnings until mothers from across the country began filing reports of significant birth defects related to Depakote, including spinal defects. Neural tube defects are the most common problems that have occurred as a result of the use of Depakote during pregnancy. Other birth defects can include spina bifida, cleft palate, facial dysmorphism, congenital cardiac defects, mental disability, limb reductions and other skeletal anomalies.

A study by the Neurological Effects of Antieplileptic Drugs (NEAD) Study Group published in the August 2006 issue of Neurology found that approximately 20.3% of pregnant women who took Depakote suffered serious adverse outcomes related to the birth of their children, while only 1% to 10.7% of pregnant women suffered problems after taking similar medications.

In October 2006, the FDA issued a "Black Box" warning on every Depakote prescription, warning of instances of serious adverse side effects including teratogenicity (the capability of producing fetal malformation), hepatoxicity (chemical driven liver damage), and pancreatitis (the inflammation or infection of the pancreas). "Black Box" warnings are issued by the FDA only when the agency has determined that a drug's side effects have the potential to cause serious injuries or death. 

The FDA further warned that valproate use during early pregnancy increased the risk of major malformations in unborn babies, including first trimester neural tube defect rates totaling 30 to 80 times higher than the rate for neural tube defects in the general U.S. population. 

The New England Journal of Medicine published a study in April 2009 that concluded that children born to mothers who took Depakote while pregnant had lower I.Q.s. The study, "Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs" was authored by Kimford J. Meador, M.D., Gus A. Baker, Ph.D., Nancy Browning, Ph.D., Jill Clayton-Smith, M.D., Deborah T. Combs-Cantrell, M.D., Morris Cohen, Ed.D., Laura A. Kalayjian, M.D., Andres Kanner, M.D., Joyce D. Liporace, M.D., Page B. Pennell, M.D., Michael Privitera, M.D., David W. Loring, Ph.D., for the NEAD Study Group. The study found that three-year-old children whose mothers had taken valproate during pregnancy had I.Q. scores that were nine points lower on average than children whose mothers had taken a different antiseizure medication, lamotrigine. The I.Q. scores of toddlers whose mothers took valporate also were lower than the scores of children whose mothers took two other antiseizure medications, phenytoin and carbamazepine.

Data from the North American Antiepileptic Drug Pregnancy Registry (NAAED) shows that the rate of major malformations in babies born to women with epilepsy taking valproate (monotherapy) is almost 4 times higher than the rate of major malformations in babies born to women with epilepsy taking a different antiepileptic drug. The NAAED Registry reported a major malformation rate of 10.7% (95% C.I. 6.3% - 16.9%) in the offspring of women exposed to an average of 1,000 mg/day of valproic acid monotherapy during pregnancy (dose range 500 - 2000 mg/day). The major malformation rate among the internal comparison group of 1,048 women with epilepsy who received any other antiepileptic drug monotherapy during pregnancy was 2.9% (95% CI 2.0% to 4.1%). Sixteen major malformations occurred in the offspring of 149 women who used valproate during pregnancy, and these malformations included neural tube defects, craniofacial defects, cardiovascular malformations and malformations involving other body systems.

The first generic versions of Abbott's Depakote delayed-release tablets, 125, 250 and 500 mg, were approved by the FDA in 2008. The generic tablets have the same safety warnings as Depakote (divalproex sodium), including a black box warning that cautions about the risk of risk of birth defects, liver damage and pancreatitis. Sun Pharmaceutical, Genpharm, Nu-Pharm, Upsher-Smith Laboratories, Sandoz, Teva Pharmaceuticals USA, Dr. Reddy's Laboratories and Lupin Limited all received approval to market the generic drug.

In April 2009, the FDA approved additional language to the Warnings section of the Depakote label in order to warn patients of an increased risk suicidal thoughts and behaviors associated with the drug's use.

Most recently, in December 2009, the FDA released a reminder for healthcare professionals that women of childbearing age should be informed that the use of Depakote could cause a wide variety of birth defects.  The FDA cited an increased risk of neural tube defects and other major birth defects, such as craniofacial defects and cardiovascular malformations, in babies exposed to Depakote during pregnancy. 

The FDA alert said that the agency is working with manufacturers to update label warnings and develop a Medication Guide to be provided to each consumer receiving the prescription.