Discussing the risks of sodium valproate
We've developed this case study with the General Pharmaceutical Council and the Nursing and Midwifery Council. While the characters are fictional, the case study is based on several people’s lived experiences, which were generously shared by patients and clinicians.
It highlights the risk of harm created by taking sodium valproate (‘valproate’), a medication for epilepsy that can cause birth defects if taken during pregnancy. Valproate was one of the interventions considered by the Independent Medicines and Medical Devices Safety Review, which reported in July 2020. The review highlighted that many women had not been properly informed about the risks of taking valproate.
Theshould mean that no more women are prescribed sodium valproate without discussing the risks of harm and having a Pregnancy Prevention Plan in place.
However, for some women already taking valproate but unaware of the risks this can create complex situations and difficult conversations with their healthcare providers.
- Be familiar with guidelines and developments that affect your work.
- Make sure any repeat prescription you sign is safe and appropriate.
- Don’t assume a patient’s already been given the information they need about risks of harm. If you haven’t personally spoken to a patient about medication they’re taking, it may be particularly important to review their decision to take it.
Dr Wright receives a repeat prescription request for sodium valproate from Millie, who is new to the practice. She sees that ahas not been completed.
After reviewing Millie’s medical record, Dr Wright becomes concerned because it appears that:
- Millie has been prescribed valproate continuously since 2010
- she hasn’t seen a neurologist since 2012
- she doesn’t appear to be on the pregnancy prevention programme (PPP).
Dr Wright wonders whether Millie has been advised about the risks of taking valproate during pregnancy. She notes that Millie’s two children were both born before 2018 when thecame into force.
This made it compulsory for GPs to make sure, each time a repeat prescription is issued, that women of childbearing potential on valproate are:
- supported by a PPP
- have an up to date, signed,
- are having an annual review with a specialist.
Dr Wright wonders whether Millie’s valproate use throughout pregnancy may have adversely affected her children.
She asks the practice receptionist to phone Millie and ask her to attend the surgery for a medication review with Dr Wright as soon as possible.
- Try to anticipate whether patients will find information distressing and, if so, be considerate when sharing it.
- Make sure that female patients on valproate are aware of the risks of taking it during pregnancy.
- Make sure female patients on valproate are aware of the need to use highly effective contraception and are referred (or referred back) to a specialist for review, annually.
At the review appointment Dr Wright confirms Millie’s medical history and checks that she takes her medication in line with prescribing instructions.
She then asks whether Millie is aware of the valproate pregnancy prevention programme (PPP). Millie says that she’s never heard of the PPP and asks why pregnancy should be prevented on valproate. She then becomes anxious, asking whether taking valproate throughout her pregnancies might have harmed her children in some way.
Dr Wright gently explains that evidence shows that, if valproate is taken during pregnancy, 1 in 10 children will have physical birth defects, and 3 or 4 out of 10 children will have developmental disorders. She asks whether Millie has any concerns about either of her children’s development.
Millie begins crying and tells Dr Wright that both of her children had been slow to speak and her health visitor at the time had been really helpful with arranging speech therapy. They are both attending the local primary school but have been struggling in some lessons, particularly her older son.
Dr Wright also asks Millie’s permission to refer her to the neurology department for review, and Millie agrees to this as well. Dr Wright gives Millie a copy of the Valproate Patient Guide .
Millie thanks Dr Wright and goes to leave. Dr Wright asks her to stay and explains that they need to discuss Millie’s options for contraception because Millie will need to comply with the valproate pregnancy prevention programme (PPP).
Dr Wright explains that part of the PPP is to take highly effective contraception, such as an intrauterine device (IUD), intrauterine system (IUS) or progestogen-only implant. Millie says it’s ok as she’s on the pill. Dr Wright replies that unfortunately the combined oral contraceptive pill (‘COC’) is not considered highly effective contraception.
Millie becomes upset again and says it’s too much to think about now and she just wants to take her valproate prescription and leave. Dr Wright says she understands but, while she prints and signs the prescription, she asks if it’s ok if the receptionist calls Millie tomorrow to make an urgent appointment to discuss the PPP and changing Millie’s contraception. Millie agrees, thanks Dr Wright for her help and apologises for getting upset. Dr Wright reassures her that it’s completely reasonable to be upset and urges Millie to contact the surgery any time if she needs to.
- Reflect on the environment, and respect and take steps to maintain a person’s confidentiality and privacy.
- Show empathy and compassion, treat people with respect and safeguard their dignity.
- Always remind women and girls about the risks of taking valproate during pregnancy, even if you’ve done it before.
- Make sure the person isn’t left without medication as people mustn’t suddenly stop taking valproate. If you’re not sure whether it’s safe to prescribe, contact the person’s GP or specialist to discuss urgently.
- Use the as a reminder of the necessary steps to take.
Millie takes her prescription for valproate to the pharmacy next door to the GP surgery. Manav is the responsible pharmacist on duty.
As Manav steps into the front of the dispensary to speak to Millie he can see that she’s been crying. Knowing he needs to ask her some potentially upsetting questions he decides to offer to speak to her in private. He explains to Millie that he needs to ask her some questions before he can dispense her medicine and suggests that they go into the consulting room. Millie agrees.
After he closes the door, Manav asks Millie whether her GP has talked to her about the risks of taking valproate during pregnancy and the need for highly effective contraception and an annual specialist review. Millie says that she’s just been told all about it, unfortunately for the first time.
She explains to Manav that she took valproate throughout both her pregnancies and has only just found out that this might have harmed her children. Manav expresses sympathy and asks whether there’s any indication that her children might have been affected. Millie says she thinks they might have been, and that she feels sick with guilt that her actions might have caused her children harm. She feels that she ought to have known about the risks.
Manav expresses sympathy and says he hopes Millie knows it’s not her fault. He tells her that hundreds of women had found themselves in a similar position over the years, despite the risks being known about for a long time.
Manav tells Millie about a public inquiry that investigated harm caused to women by three treatments, including sodium valproate. The ‘First do no harm’ in 2020. Manav offers to give Millie the details. Millie says she’d be interested to learn more about it so Manav writes down the website address together with some details of support groups and information for Millie to take away., chaired by Baroness Julia Cumberlege published its report,
Manav then goes through the questions he needs to ask when dispensing valproate:
- Is Millie on highly effective contraception?
- Is she under the care of a specialist who reviews her every year?
- Has she read the Patient Guide?
Manav can sometimes feel awkward asking these questions, especially if a woman has been coming into the pharmacy for years. But women’s circumstances may change, and he knows how important it is to check that they are fully informed about the risks.
Millie confirms that:
- She’s currently taking the combined oral contraceptive pill
- She will be booking an appointment with Dr Wright as soon as possible to discuss and arrange to have more effective contraception
- Dr Wright is referring her to the neurology department of the local hospital.
- Dr Wright gave her a copy of the Patient Guide and she will read it carefully as soon as she gets home.
After the discussion with Millie, Manav is reassured that it is safe to dispense valproate to her. If he hadn’t been sure he would have checked how much valproate Millie had left to take at home and contacted her GP or specialist urgently if necessary. This is because it’s important not to stop or change valproate abruptly as doing this can risk status epilepticus and sudden unexpected death in epilepsy.
Manav uses the Dispensary A4 poster on the wall to remind himself of the steps he must take every time he dispenses valproate to any female patient.
Millie thanks Manav for his time and for the information he’s given her and leaves the pharmacy.
- Treat people with kindness, respect and compassion.
- Encourage and empower people to share decisions about their treatment and care.
- Make sure that any information or advice you give is evidence-based.
The following week, after a telephone consultation with Dr Wright, Millie decides to have an Intra Uterine System (‘IUS’ - a Mirena coil) fitted and makes an appointment at the Family Planning Clinic. In the meantime, she attends her neurology appointment at the local hospital.
Millie is called into the consultation room by Alyssa, who explains that she’s an epilepsy specialist nurse in the neurology department. She says she understands that Millie has been referred to her by Dr Wright for an annual risk assessment and to make sure that Millie fulfils the requirements of the PPP.
Millie confirms that’s the case and says that she has an appointment later in the week to have the IUS fitted. But that she’s worried because her period is five days late. She wouldn’t usually worry about being a few days late but, while she was sitting in the waiting room, she remembered that she’d had an upset stomach about three weeks ago and wonders whether her contraception (the combined oral contraceptive or ‘COC’) might have failed. She explains to Alyssa that she’s only just found out about the harm valproate can do to a baby during pregnancy. She’s convinced that because of her actions her children may be damaged, and she can’t bear the thought she might have unintentionally harmed them.
Millie is clearly distressed, so Alyssa asks whether it would be helpful if she requested a pregnancy test to carry out today and, while they wait, outline what the next steps would be if a test were to confirm that Millie is pregnant. Millie says yes please, that would help a lot.
Alyssa says that, first of all, it’s very important that Millie doesn’t stop taking valproate suddenly because she may have a seizure. A seizure could seriously damage a baby in utero, as well as the risk to Millie herself of sudden unexpected death in epilepsy (‘SUDEP’).
Millie panics at the thought of this – she can’t afford to lose seizure control as she needs to drive for her work. She’s the only one earning since her husband’s contract ended, and they could lose their house if she couldn’t work.
Alyssa reassures Millie that, even if she made a decision to come off valproate, this would be done gradually and she wouldn’t suddenly stop being prescribed it. Whatever Millie decided to do, the neurology team (Alyssa and her consultant) would do their best to make absolutely sure her seizures remained under control. One option would be to gradually taper down the amount of valproate she was taking and then gradually introduce an alternative anti-epileptic medication such as lamotrigine or levetiracetam.
It wouldn’t be a straightforward decision. With Alyssa’s help, Millie would need to weigh the risks and benefits of remaining on valproate against the risks and benefits of exchanging it for another medication. While the final decision would be Millie’s to make, Alyssa, her consultant and Dr Wright would support Millie to understand the evidence and information about the options and would help her decide what to do.
If the test today confirms that Millie is pregnant, and she wants to continue with the pregnancy, Alyssa will refer her to a joint maternity and neurology service at the local Trust. This unit allows for early referral, particularly if a pregnancy is unplanned, to optimise anti-epileptic drug regimes. She assures her that here’s a great multidisciplinary team there and, as well as Alyssa’s neurology team, Millie would be cared for by specialist midwives, obstetricians and other healthcare professionals.
Untreated epilepsy can cause harm to both a woman and her unborn baby, so it wouldn’t necessarily be a straightforward decision for Millie. It will be crucial to carefully consider all the relevant, up-to-date, evidence-based information about the options available before reaching a decision together about what medication would be best for the patient’s specific circumstances.
There’s a knock at the door and Alyssa’s colleague comes in with the pregnancy test for Millie.
Patient support groups
Anti-convulsant Syndrome support groups
A not for profit community interest company, Connate support supports families affected by substances that have harmed the foetus.
This website hosts both:
- the which provides information and support to patients, parents, carers and health professionals
- and their sister support organisation, the National Helpline 01253 799 161.
The Organisation for Anti-convulsant Syndrome charity is for those that have been touched by the effects of medications such as sodium valproate.
- UK Helpline: 07904 200364
- Email: email@example.com
Valproate Victims UK
A membership organisation, Valproate Victims UK is for those affected by valproate in pregnancy.
- Public Facebook page containing regular updates
Epilepsy patient support groups
A national charity and community of people fighting for a better, fairer future for all people with epilepsy. Epilepsy Action provides support and expert advice, improves healthcare and campaigns for change.
- Helpline: 0808 800 5050
- email: firstname.lastname@example.org
A national charity, Epilepsy Society carries out epilepsy research and support.
- Helpline: 01494 601400
- email: email@example.com
A national charity and community of families and clinicians, SUDEP Action works to tackle issues around SUDEP (sudden unexpected death in epilepsy) and all epilepsy-related deaths.
- Tel. 01235 772850
- email: firstname.lastname@example.org
They have also developed standardised safety tools for clinicians and women to support positive conversations about minimising epilepsy risks and SUDEP:
- SUDEP and seizure safety checklist is a free evidence based tool supporting clinicians in discussing risk with people with epilepsy
- EpSMon is an award-winning app that helps people with epilepsy self-monitor in between visits to the doctor.
Guides and resources for patients
Reports and reviews
- First do no harm - published by The Independent Medicines and Medical Devices Safety Review in 2020
- Antiepileptic drugs: review of safety of use during pregnancy - published January 2021
- Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2016-18 - published by the Maternal, Newborn and Infant Clinical Outcome Review Programme (MBRRACE-UK) on the website of Oxford University’s National Perinatal Epidemiology Unit (NPEU) in January 2021.
Guidance and resources
For all health professionals
The 2020 ‘pan-college’ Guidance document on valproate use in women and girls of childbearing years. This informs all healthcare professionals of best practice and supports them to navigate situations that could arise. Further updates will be available on the websites of both:
- MHRA Booklet: Guide for healthcare professionals
- Annual Risk Acknowledgement Form
- MHRA press release
- Drug Safety Update
- Good medical practice, in particular paragraphs 11 and 12
- Decision making and consent, in particular paragraphs 58, 12 and 20
- Standards for Pharmacy Professionals
- A4 dispensary poster for use in pharmacies . This has key information about the Pregnancy Prevention Programme (PPP)
- General Pharmaceutical council statement on supplying valproate safely to women and girls
- Focus on supplying medicines safely: sodium valproate. General Pharmaceutical council article published in 2018
- Royal Pharmaceutical Society guidance: Valproate and the pregnancy prevention programme