Why ARE women with migraines being treated with a drug linked to birth defects?
TWELVE weeks into her fifth pregnancy, Nikki Mason, then 28, was prescribed a drug that would change her life for ever. She had been diagnosed with bipolar disorder the previous year, but had come off her treatment — the antipsychotic drug Risperdal — because she was trying to conceive and was worried about sideeffects for the baby.
However, once she was pregnant, her psychiatrist prescribed a different, moodenhancing drug: sodium valproate (despite the fact that she had no symptoms of depression).
The decision has had devastating consequences for Nikki’s daughter, Naomi. Now 12, Naomi has learning difficulties, poor language skills, a thin top lip and a double squint — classic signs of what’s known as foetal valproate syndrome.
Although valproate can be a very effective drug for treating symptoms of epilepsy and bipolar disorder, it can have serious detrimental effects on a growing foetus.
Babies exposed to the drug have a 30 to 40 per cent risk of serious developmental disorders, including low IQ, and an 11 per cent risk of physical defects.
Exactly how valproate harms the baby is unclear: it may trigger changes in heart rhythm, starving the unborn baby of oxygen, or cause a deficiency in folic acid, linked to spina bifida.
Campaigners claim that regulators knew of the problems as far back as 1973 — yet it was not until 2015 that clear warnings were published.
In the meantime, valproate has been prescribed, without any warnings, to women of childbearing age with epilepsy — it is estimated that 20,000 British children have been harmed because their mothers took the drug during pregnancy.
Despite the risks, the use of valproate in women aged 15 to 49 has remained widespread, with one in five of the 2,298,000 prescriptions issued between 2010 and 2012 in the UK — nearly half a million — given to women in this age group, according to figures from the manufacturer Sanofi.
To date, the focus on the risks of valproate in pregnancy has centred on women prescribed it for epilepsy.
But now, Good Health can reveal that tens of thousands of other women who have bipolar disorder and migraine have also been prescribed it and put at risk.
This is despite official guidelines that the drug should not be routinely prescribed to women and girls with epilepsy or bipolar ‘ unless other treatments are ineffective or not tolerated’.
JUST like women with epilepsy, many of these patients have not been told of the dangers, either. Almost one in five women taking the drug for epilepsy still don’t know that it can harm their unborn child if they become pregnant, according to a survey by a group of epilepsy charities.
Also, twothirds of these women have not received a valproate leaflet issued in February 2016 by drug regulator the Medicines and Healthcare products Regulatory Agency (MHRA) to raise awareness of the risks.
Alarmingly, some women still receive repeat prescriptions of the drug from their pharmacist in a plastic bag with no patient information leaflet, it was claimed at a European Medicines Agency (EMA) hearing last September.
With some doctors still not warning women of the risks, the EMA launched an inquiry last year into whether further regulatory action was needed.
But tens of thousands of other women have also not been warned of the dangers.
Between 2010 and 2012, more than 87,000 prescriptions of one brand of valproate were issued to women aged 15 to 49 for bipolar disorder and more than 3,000 for migraine. Indeed, as many as one in four women under 50 with bipolar disorder was prescribed valproate, according to a survey by the Prescribing Observatory for Mental Health UK.
In the vast majority of cases, this was at a dose ‘associated with a substantial risk of harm to an unborn child’, said the survey, published by the Royal College of Psychiatrists in 2016. ‘This suggests that not all prescribers may be aware of the teratogenic potential of valproate’ — i.e., the damage to unborn babies.
Furthermore, 45 per cent of these women received no ‘documented evidence’ of the importance of using contraception while on the drug; half were not warned of the congenital defects it can cause; and 76 per cent were not warned of the longterm developmental problems. The survey reveals ‘poor compliance’ with official prescribing guidelines.
More needs to be done to protect women, says Dr Sarah Jones, a consultant perinatal psychiatrist at Wythenshawe Hospital in Manchester. ‘ NICE [National Institute for Health and Care Excellence] guidelines issued in 2007 and 2014 state that valproate should only be prescribed to women of childbearing potential in exceptional circumstances; if they haven’ t responded to other medication and are aware of all of the risks in pregnancy. Despite this, there are still women taking valproate without an awareness of the risks in pregnancy.’
Janet Williams, chief executive of InFACT, the Independent Fetal AntiConvulsant Trust charity, which supports victims of the drug, adds: ‘We already know valproate is prescribed for thousands of women for epilepsy, however there is a high prescription rate for bipolar, too.
‘ The risks of valproate in pregnancy have been known of by governing bodies since 1973, yet we know that around 70 per cent of female valproate patients are still not warned about the risks to women of childbearing age and we are very concerned about the outcome this may have for women prescribed it for bipolar disorder.’
According to the charity Bipolar UK, valproate is a ‘continuing issue’ for women with bipolar. ‘Some say they were warned of the risks years before and some say they have never received any information,’ said a spokeswoman.
In April, the MHRA announced it had changed the licence of valproate so it can no longer be prescribed to women of childbearing age unless they sign a form saying they understand the risks.
A new warning will also appear on the packet and the drug will be distributed in smaller packs, to encourage monthly prescribing.
It comes after the EMA endorsed a similar ban earlier this year.
But, while this is a welcome move, there are still many who’ve been given the drug and who are living with the consequences of the failure to warn them of the potential risks. Their situation bears similarities to other medical devices and treatments regulated by the MHRA, where women have reported ongoing problems, but their complaints have fallen on deaf ears.
Following a campaign led by the Mail, Baroness Julia Cumberlege, a former health minister, has been asked to chair a review into the official response to patients’ concerns in three areas — vaginal mesh (used to treat incontinence), birth defects caused by Primodos ( a hormonebased pregnancy test) and birth defects linked to sodium valproate.
(Campaigners are also hoping the review will look at Essure, a birth control implant, which, as Good Health has reported, has been known to disintegrate and cause debilitating allergic reactions.)
With valproate, the focus has been on women with epilepsy. However, as we reveal today, a proportion of women with other conditions have been affected — such as Nikki Mason.
SHE says: ‘ From a baby, I could tell that something wasn’t quite right with Naomi. She didn’t babble and her speech was delayed.
‘All her problems were attributed to learning difficulties. I felt there was something more — but my concerns were always dismissed.’
She is convinced that valproate is to blame. ‘ There is no other possible explanation. I have four other children, aged 16 to 24, none of whom has these problems,’ says Nikki, now 41, of Bishop Auckland, County Durham, who is married to David.
She was prescribed valproate by her psychiatrist as a ‘safe option’ during pregnancy. ‘I didn’t have any symptoms, but he wanted to put me on medication to keep me stable,’ says Nikki. ‘ As the pregnancy developed and I got heavier, the doses of valproate got higher.’
She took the drug for eight years.
‘I stopped taking it because it felt like it was turning my brain to mush. That’s when I looked up the drug and its sideeffects online and I first found out about the risks during pregnancy. I feel so guilty and angry.
‘When I raised foetal valproate syndrome with my GP, he didn’t seem to know anything about it. However, when I mentioned it to a paediatrician, he said Naomi’s problems could be caused by the drug.’
In the past six months, solicitor David Gazzard, of Swindonbased firm BLB, has been contacted by 50 people affected by valproate, including women who took it for epilepsy and bipolar disorder and who have affected children.
He will check what advice they were given by doctors.
Meanwhile, campaigners want a compensation scheme for the victims — and a public inquiry into the regulation and licensing of medical products within the UK.
Speaking at the EMA hearing last year, Dr Eric Teo, who is in charge of drug safety at Sanofi, said: ‘Sanofi has always provided the most uptodate scientific information, with the approval of the health authorities. There is a consent form for doctors to review with patients, there are patient cards to take home and there is also a prominent warning on the outside of the box.’
The MHRA says patients should not stop taking the medicine without consulting their doctor.