Sodium valproate and women - the dilemma
The headlines often speak louder than the research, but here Epilepsy Society's medical director, Professor Ley Sander discusses why some women with epilepsy are still prescribed sodium valproate and his hopes that one day genetic testing will help individuals decide whether it is safe to take during pregnancy.
'We often talk about targeted treatments and the importance of genetic research in ensuring that in the future, people with epilepsy receive the medication that suits them best, right from the point of diagnosis.
In the same way that a person's genetic blueprint can determine their risk of developing epilepsy, it can also determine the way they respond to and tolerate different anti-epileptic drugs (AEDs). At Epilepsy Society, this is one of our key areas of research.
Nothing highlights the importance of such research more acutely than the management of women and girls of childbearing years, more particularly those who have idiopathic generalised epilepsy.
Better seizure control
One of the most effective medications for all seizures in this type of epilepsy - absence, myoclonus and tonic clonic - is sodium valproate. Fifty years after it was first licensed in the early 1960s, it is still one of the most widely prescribed anti-epileptic drugs in the world. And its track record speaks for itself.
In 2007 SANAD, a major study by the University of Liverpool found that those who were treated with sodium valproate had a significantly better outcome in terms of seizure control than those who were prescribed carbamazepine, topiramate or phenobarbital.
But sodium valproate comes with a warning. It is teratogenic. This means that children whose mothers are prescribed the drug during pregnancy are at a higher risk of malformation and they may also be at risk of developing autism and other neuro-developmental disorders.
Sodium valproate and developing foetus
A study by the University of Liverpool's Institute of Translational Medicine showed that children exposed to valproate alone in the womb were six times more likely to be diagnosed with a neurological disorder than those whose mothers were taking other epilepsy drugs.
When mothers were taking valproate alongside other AEDs, children were 10 times more likely to develop a neurological disorder.
Furthermore, studies show that sodium valproate exposure during pregnancy can increase the incidence of physical defects such as a hole in the heart, cleft lip and cleft palate. The risk of spina bifida is also much higher than in the background population.
For some women, sodium valproate may be the only drug that will effectively control their seizuress. Under no circumstances should a woman suddenly stop taking her drugs without consulting her GP or neurologist.
Genetic response to drugs
At the moment we do not know why sodium valproate causes neurological disorders or physical defects in some babies but not others. We suspect that the mother's genetic make-up may determine response to the medication and the risk of their baby being adversely affected.
Research has already established a link between a person's genes and their risk of developing a severe rash from another commonly prescribed AED, carbamazepine, but we're not there yet with sodium valproate.
So why then is there not a blanket ban on prescribing sodium valproate to women and young girls? The answer is that for some women, sodium valproate may be the only drug that will effectively control their seizures, and seizures are not benign events. Under no circumstances should a woman suddenly stop taking her drugs without consulting her GP or neurologist.
The developing foetus seems generally resistant to seizures. There is no evidence that simple partial, complex partial, absence or myoclonic seizures are harmful to the unborn child. However, in some circumstances, tonic clonic seizures may cause miscarriage, trauma related to falls and blood conditions that can affect the developing baby - foetal hypoxia affecting oxygen levels or acidosis affecting acidity levels.
The risk of sodium valproate has to be assessed against the risk of seizures to both the mother and baby.
NICE guidelines for epilepsy
The NICE clinical guidelines for the diagnosis and management of the epilepsies in adults and children are very clear. Healthcare professionals should discuss the risks of sodium valproate with women and young girls, making clear the potential outcome of higher doses of the drug and the increased risk of taking several anti-epileptic drugs including sodium valproate.
If sodium valproate remains the treatment of choice then a woman should be given all the support and information necessary to help her make an informed decision about starting a family.
These are not easy decisions. As is so often the case with epilepsy, there is a delicate trade off between seizure control and side effects. For women hoping to start a family or in the early stages of pregnancy, the health of the unborn child is a pivotal part of the equation.
I look forward to the day when a simple genetic test will be able to assess a woman's risk of having a baby with developmental or physical disorders and will be able to reassure her that if sodium valproate is the only drug that will control her seizures, she won't be endangering her unborn child.'
Professor Ley Sander was writing in Epilepsy Society's magazine, Epilepsy Review, Issue 8, Autumn 2013. Find out how to subscribe.