Valproate, an anti-seizure drug used for epilepsy, bipolar disorder and sometimes migraine, now has stricter UK prescribing rules. The UK regulator, the MHRA, limits starting it in women and men under 55. That is because some babies are still exposed to it in the womb each year. The update raises the question of whether US rules should follow.
Summary: The UK MHRA recently updated its guidelines. They make it quite hard for doctors to prescribe valproate to women and men under age 55. Valproate is often used to treat epilepsy, bipolar disorder and sometimes even migraine. The update came because a small number of newborns are still exposed to the drug in the womb each year.
Experts are raising safety concerns about a common anti-seizure drug. UK guidelines now bar prescribing valproate to men or women younger than 55 years of age. So should the US also update its guidelines?
The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has issued new guidance. It bans valproate in male and female patients under age 55 unless two independent experts find it necessary.
Valproate is used for more than seizures or epilepsy. It is also used for bipolar disorder. It may sometimes be used for migraine headaches too.
There is a reason UK regulators updated their guidelines. Evidence keeps growing that this drug causes birth defects, including neural tube defects (defects of the brain and spine), in children of mothers exposed to it. It also seems to raise the risk of these birth defects even if the father took the drug within three months before conception.
But not everyone agrees with such strict guidelines. The drug works well to control seizures. Some researchers think UK regulatory agencies have gone too far without weighing other factors.
In the US, guidelines do not seem to be changing. Experts say it has long been known that valproate causes congenital disabilities, and some of the most reliable studies came out more than 15 years ago.
Also, the American Epilepsy Society (AES) already has very clear guidelines. They bar giving the drug to women planning to get pregnant.
So why did UK regulators make these recommendations? There seems to be a reason. Earlier guidelines to avoid prescribing it to women planning pregnancy helped, but not as much as hoped. Experts say valproate use has dropped in women of childbearing age, yet it is still a major issue. Two to three babies are still born in the UK each month who were exposed to this toxic drug in the womb.
So women are still not being told enough about the risks of this drug. It is vital to know that valproate has been used for bipolar disorder and epilepsy for several decades. It is generally quite safe. It is unsafe only for one specific group.
Health experts in the US think a strict ban like the UK’s is a bad idea. They say a ban would make things hard for doctors, who often prescribe this drug when other options have failed. So a strict valproate ban may also have harmful effects.
US experts say they know the risks well. The first evidence of neural tube defects in babies of mothers exposed to valproate came out in the 1980s. So good guidelines are already in place to keep this drug away from women who plan to get pregnant. Since these side effects were found, valproate use has dropped a lot in women with epilepsy.
Experts also note that a UK-style ban would make it hard for doctors to prescribe the drug to women who do not plan to have more children. Many women with epilepsy may not want to get pregnant at all, for many reasons.
US experts also doubt such rules for men. There is growing evidence of more brain development disorders in children of men who took valproate three months before conception. But most of that data comes from weak look-back studies.
In short, US experts say they do not need a ban like the UK’s. But they agree that valproate needs stronger warnings.
Frequently asked questions
What is valproate used for?
Valproate is an anti-seizure drug used to treat epilepsy and seizures. It is also used for bipolar disorder, and doctors sometimes consider it for migraine headaches. It has been used for bipolar disorder and epilepsy for several decades, and it is generally quite safe. The danger is limited to one group: babies exposed to the drug before birth.
Who should not take valproate?
Women who plan to get pregnant should not take valproate. The American Epilepsy Society guidelines bar giving it to them. In the UK, the MHRA now bars prescribing it to men and women under 55 unless two independent experts find it necessary. The UK rule covers men because exposure within three months of conception also seems to raise the risk to the child.
What birth defects can valproate cause?
Valproate taken during pregnancy can cause birth defects, including neural tube defects, in the baby. The first evidence of neural tube defects in babies of mothers exposed to valproate came out in the 1980s. There is also growing evidence of brain development disorders in children of fathers who took valproate in the three months before conception. But most of that data comes from weak look-back studies.
Is valproate banned in the United States?
No. US guidelines are not changing. US experts say the risks have been known for decades. Rules already keep the drug away from women planning pregnancy, and use in women with epilepsy has dropped a lot. They warn that a UK-style ban would make it hard to prescribe valproate when other treatments have failed. But they agree it needs stronger warnings.
Related reading
Opioid Exposure in Pregnancy and Fetal Brain Size · Once-daily anti-epileptic drug for Alzheimer's · Drug Addiction Treatment, St. Louis