As experts voice concerns over new UK guidelines that restrict valproate use in women and men younger than 55 years owing to safety risks, the question arises: Should the US consider updating its own guidelines in response?
On January 31, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has issued new guidance, banning the use of valproate in new female patients under 55 unless two independent specialists agree that no other effective or tolerated treatment is available. This same level of agreement is also required for existing female patients to continue current valproate treatment.
These requirements were introduced due to substantial research showing an increased risk of major congenital malformations in offspring when mothers use the drug during pregnancy. The restrictions also apply to men, because there is a potential increased risk for neurodevelopmental disorders in offspring if fathers take the medication within 3 months of conception.
However, an editorial published in February in The Lancet Neurology says the guidance goes too far and omits key information.
“In a drastic move that no other country has taken yet, the [MHRA] has introduced new stringent guidelines for valproate use,” the editorialists write. “The move…will create multiple challenges for healthcare providers and people with epilepsy.”
Contacted for comment on the UK initiative, the American Epilepsy Society (AES) told Medscape Medical News in a statement that the “teratogenic risks of valproate are well established, and this [UK] regulatory change is not based upon new evidence.”
Therefore, the organization “is not recommending any changes to current valproate prescribing regulations in the United States,” the AES said. Its current position statement was last updated in 2021.
Why Now?
Although valproate is primarily used to manage epilepsy, it is also approved for the treatment of bipolar disorder.
The Lancet Neurology editorial notes that recent data show that from 2018 to 2022, there was a significant reduction in the number of pregnant women prescribed the drug in the UK.
So why did the MHRA take the decision to update its guidelines? What prompted the agency to proceed with what the editorial describes as a “controversial decision”?
In a written response to Medscape Medical News, the agency explained that despite a 38% reduction in valproate use among women of childbearing age since 2018, approximately two to three babies a month continue to be born with in utero exposure to the medication.
“Evidence from patient support groups makes it clear that some women on valproate are still not being [adequately] informed about the risks by their healthcare professionals,” the MHRA noted.
“The new measures will provide additional scrutiny on the prescribing of valproate, which should ensure that valproate is only initiated when there are no other effective or tolerated treatment options,” the agency added. On the basis of substantial research, “there is no safe dose of valproate in pregnancy.”
In response to concerns raised in the Lancet Neurology editorial — including the lack of recommendations on alternative medications and the potential burden of requiring two independent specialists, which could strain already busy neurology clinics — the MHRA explained that it had engaged in extensive discussions with the Commission on Human Medici
