Depakote Pregnancy Use Linked to Developmental Disorders, Study Warns

New data adds to growing evidence linking the epilepsy drug to an increased risk of neurological and attention disorders in children exposed to Depakote in utero.

New research has uncovered what appears to be more evidence linking the use of Depakote and similar anti-seizure medications during pregnancy with an increased risk of a child developing disorders like autism and attention-deficit hyperactivity disorder (ADHD).

A team of researchers from Brigham and Women’s Hospital, Harvard Medical School and Stanford published a report in The BMJ on March 11, warning that children exposed to Depakote in the womb were found to have higher rates of neurotypical disorders. They also warn that similar signals from Zonegran may call for a closer look by the scientific community as well.

Depakote Pregnancy Risks

The U.S. Food and Drug Administration (FDA) approved Depakote (valproate) in 1983 to treat epilepsy, bipolar disorder, depression and migraine headaches. However, growing safety concerns led the agency to add a “black box” warning in 2006, after data showed that about 20% of children born to mothers who took the drug during pregnancy had birth defects or malformations. 

In May 2013, the FDA strengthened those warnings, contraindicating Depakote use during pregnancy for migraine treatment.

Concerns about long-term neurodevelopmental risks have continued to mount. A 2020 study by Indiana University researchers found that prenatal exposure to Depakote doubled the risk of autism or ADHD. A 2022 study reported that epilepsy drugs such as Depakote and Topamax may increase the likelihood of autism and intellectual disability when taken during pregnancy.

More recently, a 2024 Harvard study reinforced those findings, linking Depakote use during pregnancy to a higher risk of autism. Late last year, another study suggested the risks may extend further, finding that children of men who used Depakote had a 50% higher risk of neurodevelopmental disorders.

This latest study was headed by Loreen Straub, an instructor at Brigham and Women’s Hospital. Her research team conducted a cohort study using data on insured beneficiaries in the U.S. from 2000 to 2021. They analyzed data involving nearly 2.5 million pregnancies, finding 7,245 cases where women with epilepsy did not take antiseizure medications and 10,345 pregnancies where the expecting mother took at least one such medication during her term.

The research team looked at data on pregnant women who used a variety of epilepsy drugs, including Depakote, Zonegran, Keppra, Tegretol, Epitol, Vimpat, Lamictal, Topamax, Dilantin and phenobarbital. Of those, researchers found signals of an association between pregnancy use and neurodevelopmental disorders (NDDs) between Depakote and Zonegran.

According to the findings, Depakote was linked to an increased risk of all neurodevelopmental disorders, as was Zonegran. However, the study noted that Zonegran’s numbers were uncertain due to a low number of children exposed to it, whereas Lamictal and some other medications only saw slight rises in the risk of increased intellectual disability.

Researchers found no increased risks linked to either Keppra or Dilantin.

“The observed risk increase for all NDDs after valproate exposure aligns with previously described fetal neurotoxic effects of the drug. For levetiracetam, lamotrigine, phenytoin, and topiramate, our findings indicate no substantial risk increase. One potential exception is intellectual disability, for which a risk increase was observed for lamotrigine and topiramate, as well as for oxcarbazepine, valproate, zonisamide, and phenobarbital.”

– Loreen Straub, Prenatal antiseizure drug exposure and risk of neurodevelopmental disorders in children: population based cohort study

The authors determined that the findings support previous scientific evidence linking Depakote to an increased risk of neurodevelopmental risks and suggested that Zonegran requires further scientific evaluation. They called for continued monitoring of newer antiseizure mediations to understand and better detect pregnancy use risks.

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