A new review suggests that men taking the epilepsy drug valproate do not appear to increase the risk of birth defects or developmental disorders in their children. Valproate is known to cause these issues when taken by pregnant women, but this study, published in the Journal of Neurology Neurosurgery & Psychiatry, indicates a different outcome for paternal use.
The research team, led by Professor Piero Perucca from the University of Melbourne, Australia, conducted a systematic review of 10 studies. Their analysis revealed that "evidence for any risk to the offspring resulting from paternal exposure to anti-seizure medications is scarce and inconsistent, with most studies showing no increased risk compared with unexposed controls." They concluded that the available evidence does not justify major concerns.
Concerns and Regulatory Responses
Previous experimental animal studies have raised concerns, linking anti-seizure drugs to male infertility, birth defects, and developmental delays. This led the U.K.’s Medicines and Healthcare Products Regulatory Agency to prohibit valproate use for anyone under the age of 55 who might become a new parent.
The researchers, however, questioned the wisdom of these regulatory changes. They argue that restricting valproate could result in the prescription of less effective medications, particularly for individuals with generalized epilepsies where valproate is often the most effective option. The team noted that not prescribing valproate to men could increase the risk of disease and death, including sudden unexpected death in epilepsy (SUDEP).
Expert Commentary
Torbjorn Tomson, with the Karolinska Institute, agreed that the pooled evidence provides essential and mainly reassuring information, indicating no increased risks for developmental disorders with paternal valproate exposure. In an editorial published alongside the study, Tomson stated, "It is questionable to refer to the [U.K.’s] restriction as a precautionary measure when they place male patients with generalized epilepsies at risk of inadequate seizure control with potentially fatal consequences."
Need for Further Research
Despite the reassuring findings, the researchers emphasized the need for more investigation. "While the findings summarized in our systematic review are overall reassuring for males taking anti-seizure medications including valproate, it is clear that the potential reproductive implications of anti-seizure medication exposure in males remain an under-investigated area of research that should be prioritized over the next decade," the study authors wrote.
