Study Warns About Autism from Depakote, Similar Antiseizure Drugs When Used During Pregnancy

The findings of a new study appear to add to the growing body of evidence that antiseizure medications, like Depakote, can increase the risk of a child developing autism following exposure before birth.

Harvard researchers report that children with prenatal exposure to antiseizure medications faced an increased risk of autism spectrum disorder, with the highest risk being linked to Depakote. The findings were published on March 21 in The New England Journal of Medicine.

Drugs like Depakote (valproate), Topamax (topiramate) and Lamictal (lamotrigine) are often prescribed to women suffering from epilepsy, especially during pregnancy, where a sudden seizure could result in injury to the mother and child. However, side effects of using the drugs during pregnancy, particularly Depakote, have previously been linked to a number of potential health concerns, primarily involving unborn children who suffer birth defects after being exposed to the medication before birth.

Abbott Laboratories and AbbVie, a subsidiary it spun off, have faced hundreds of Depakote lawsuits in prior years, involving allegations that the drug maker failed to warn women and the medical community about the risks associated with using Depakote during pregnancy.

In this latest study, researchers looked at data from a population-based cohort of pregnant women and their children from 2000 through 2020, looking for exposure to Topamax, Depakote or Lamictal from the 19th week of gestation until delivery.

According to the findings, the estimated incidents of autism spectrum disorder diagnoses for children eight years of age was 1.9% out of data on more than 4 million children. Among mothers with epilepsy, that rate increased to 4.2%, even when the children had no exposure to antiseizure medication.

However, when the antiseizure medications were accounted for, that number changed significantly, with 6.2% of those exposed to Topamax developing autism, and those exposed to Depakote prenatally facing a 10.5% risk. Those whose mothers took Lamictal faced a 4.1% increased risk.

“The incidents of autism spectrum disorder was higher among children exposed to the studied antiseizure mediations than in the general population,” the researchers concluded. “However, after an adjustment for indication and other cofounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate.”

Depakote Pregnancy Risks

The findings are the latest in years of research linking Depakote to birth defects and other pregnancy complications.

A study published in JAMA Neurology in 2022 found significantly increased risks of children developing autism and other intellectual disabilities after exposure to Depakote and Topamax during pregnancy. Overall, the two drugs were linked to a two to four-fold increased risk of ASD and intellectual disability.

In April 2018, the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) barred doctors in that country from prescribing Depakote to women of childbearing age unless they are on a pregnancy prevention program.

According to the MHRA, up to 40% of babies born to mothers who take Depakote are at risk of developmental disorders, and 10% are at risk of birth defects.

Another epilepsy drug study published in February 2018 in JAMA Neurology, by researchers from Denmark again, found that children who were exposed to Depakote in the womb scored lower on language and math tests in the sixth grade, when compared to their peers.

In 2006, the FDA added a “black box” warning about potential Depakote pregnancy side effects, after a study found that 20% of pregnant mothers who gave birth while on Depakote had a child with malformations or a birth defect.

In May 2013, the FDA put new restrictions on Depakote pregnancy use, contraindicating it for pregnant women, but only when it was used for the treatment of migraines. The agency did not contraindicate it for pregnant women using it to treat epilepsy. The FDA changed all valproate-based drugs from a class “D” to a class “X” pregnancy drug, but only as they pertain to migraines.

Before the drug’s patent expired in 2007, Depakote was a blockbuster drug generating about $1.5 billion in annual sales for AbbVie’s predecessor.