Discussing the risks of sodium valproate

This case study is about discussing the risks and benefits of taking sodium valproate (‘valproate’) with a patient who’s been prescribed it for several years. This case study focuses on the risk to patients who may become pregnant while taking valproate-containing medication to manage epilepsy, but the balance of risks and benefits will be different for each individual patient.

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, a medication for epilepsy and bi-polar disorder 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.  

The Medicines and Healthcare products Regulatory Agency (MHRA)’s strengthened regulatory position should mean that patients of reproductive potential should only be prescribed valproate if the following applies:

  • The patient has discussed the risks with two specialists, both of whom agree that there is no other effective or tolerated treatment
  • The patient is fulfilling the requirements of the Pregnancy Prevention Programme (PPP), where appropriate.

However, for some people already taking valproate but unaware of the risks in pregnancy this can create complex situations and difficult conversations with their healthcare providers.

This case study relates to valproate use by a female patient. In 2024, MHRA communicated the results of a retrospective observational study which indicates an association between valproate use by men around the time of conception and an increased risk of neurodevelopmental disorders in their children. The MHRA have issued a Drug Safety Update (DSU) which clarifies their advice when prescribing valproate for men. The DSU confirms that a two specialist review of medication isn’t required for men already taking valproate. MHRA also recommend that men of childbearing potential and their partners use effective contraception during valproate treatment and for at least 3 months after stopping valproate.

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Repeat prescription (GP)

Repeat prescription (GP)

Learning overview

  1. Keep up to date with guidelines and developments that affect your work.
  2. Make sure any repeat prescription you sign is safe and clinically appropriate.
  3. Don’t assume a patient has 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.

Scenario

Dr Wright receives a repeat prescription request for sodium valproate from Millie, who is new to the practice. She sees that a valproate Annual Risk Acknowledgement Form (ARAF) has 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).

In Millie’s medical record Dr Wright reads that Millie has given birth to two children. She wonders whether Millie has ever been advised about the risks of taking valproate during pregnancy. She notes that Millie’s two children were both born before 2018 when the MHRA’s strengthened regulatory position came into force, and before the MHRA issued additional regulatory measures in 2023.

Under the current MHRA regulatory measures it is the responsibility of GPs to make sure, each time a repeat prescription is issued, that people of childbearing potential on valproate: 

  • Are fulfilling the requirements of a PPP
  • Are having an annual review with a specialist.
  • Have an up to date, signed, Annual Risk Acknowledgement Form (ARAF)
  • Are aware of the risks of valproate, if taken during pregnancy
  • Are using effective contraception
  • Have been given the valproate patient guide, or know how to access it online
  • Know they must contact their GP urgently for a referral to a specialist if pregnant

Dr Wright wonders whether Millie’s valproate use throughout pregnancy may have adversely affected her children.

She asks the practice receptionist to contact Millie and ask her to attend the surgery for a medication review with Dr Wright as soon as possible.

Medication review (GP)

Medication review (GP)

Learning overview

  1. Try to anticipate whether patients will find information distressing and, if so, be considerate when sharing it.
  2. Make sure that patients of childbearing potential on valproate are aware that any benefit for them of taking valproate must be considered alongside the risk of harm of taking it during pregnancy.
  3. Make sure patients of childbearing potential on valproate are aware of the need to use effective contraception and are referred (or referred back) to a specialist for review annually.
  4. Support patients to understand that the balance of risk and benefit means that they shouldn’t stop taking valproate without medical support.

Scenario

At the review appointment Dr Wright confirms Millie’s medical history. She asks whether there have been any changes in Millie’s epilepsy management 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, it can cause some difficulties with the way a baby develops. 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 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 says that, if Millie would like, she could write a letter to the school, explaining the situation so that Millie could speak to them about whether a referral to an educational psychologist might be appropriate. Dr Wright asks a few more questions about the children and decides, with Millie’s consent, to refer them for assessment by a community paediatrician. 

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 fulfil the conditions of the valproate pregnancy prevention programme (PPP). 

Dr Wright explains that part of the PPP is to use 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’) on its own may not always prevent pregnancy. Dr Wright advises Millie that she should use an additional contraceptive method in addition to the pill, such as a condom.

Millie’s upset by this information 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 appreciates that it must be very difficult for Millie to take in all this information. She explains that it’s important for Millie to keep taking valproate until she’s had a review with the neurology department, as the medication is effectively controlling her seizures. While Dr Wright prints and signs the prescription, she asks if it’s ok if the receptionist calls Millie the next day to make an urgent follow up appointment to discuss the PPP and options for strengthening her contraception once Millie has had time to think about the information she’s been given. Millie agrees, thanks Dr Wright for her help and apologises for getting upset. Dr Wright reassures her that it’s totally understandable to be upset and emphasises to Millie that she can contact the surgery any time she needs to.

Community pharmacy (pharmacist)

Community pharmacy (pharmacist)

Learning overview

  1. Reflect on the environment, and respect and take steps to maintain a person’s confidentiality and privacy.
  2. Show empathy and compassion, treat people with respect and safeguard their dignity whilst providing patient-centred care.
  3. Give the person all relevant information in a way they can understand, so they can make informed decisions and choices. This could be the paper patient card and patient guide, or the QR code on some patient information leaflets.
  4. Always remind patients of child bearing potential about the risks of taking valproate during pregnancy and check that they’ve been made aware to always use effective contraception, even if you’ve done it before.
  5. 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 dispense, contact the person’s GP or specialist to discuss urgently.
  6. Dispense all valproate prescriptions in their original packaging as they include specific warnings and pictograms, including a patient card and Patient Information Leaflet. Pharmacists can supply up to 10% more or less than the prescription so that they can dispense a manufacturer’s original full pack.
  7. In exceptional circumstances where a patient needs to receive their medication in different packaging, always provide a copy of the package and Patient Card, and add a valproate warning sticker to the outer box.
  8. Display the Pharmacy A4 Poster in the dispensary and use as a reminder of the necessary steps to take.

Scenario 

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 a Pregnancy Prevention Programme 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 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 have 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 Independent Medicines and Medical Devices Safety Review, chaired by Baroness Julia Cumberlege published its report, ‘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. 

Manav then goes through the questions he needs to ask when dispensing valproate:

  • Is she under the care of a specialist who reviews her every year?
  • Does Millie know the risk of taking valproate during pregnancy?
  • Is she taking effective contraception?
  • Has she read the valproate Patient Guide?

Manav can sometimes feel awkward asking these questions, especially if a patient has been coming into the pharmacy for years. But circumstances may change, and he knows how important it is to check that patients are fully informed about the risks.

Millie confirms that:

  • She’s currently taking the combined oral contraceptive pill and will use condoms as well, following Dr Wright’s advice
  • 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 pharmacy A4 poster on the wall to remind himself of the steps he must take every time he dispenses valproate to any female patient. This includes giving Millie the patient guide.

Millie thanks Manav for his time and for the information he’s given her and leaves the pharmacy.

Neurology (epilepsy specialist nurse)

Neurology (epilepsy specialist nurse)

Learning overview

  1. Treat people with kindness, respect and compassion.
  2. Encourage and empower people to share decisions about their treatment and care.
  3. Make sure that any information or advice you give is evidence-based.

Scenario

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.

Later, 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. She says that once they’ve gone through the Annual Risk Acknowledgement Form (ARAF) together, a second specialist will need to independently consider and document on the form whether valproate remains appropriate because there is no other effective or tolerated treatment. Millie won’t need another consultation as Alyssa will send the form electronically to the consultant neurologist.

As they talk through the risks of valproate to unborn babies, Alyssa asks if Millie is fulfilling the PPP requirements. Millie confirms that’s the case and says that she has an appointment later in the week to have the IUS fitted.

But Millie says 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 have been affected, 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, to discuss what the different options would be if a test were to confirm that Millie is pregnant. Millie says yes please, that would help a lot.  

Alyssa says that, if Millie is pregnant, it’s very important that Millie doesn’t stop taking valproate suddenly because she may have a seizure. A seizure could raise Millie’s risk of sudden unexpected death in epilepsy (‘SUDEP’), as well as potentially harming a baby in utero.

Millie panics at the mention of stopping valproate and having a seizure – she realises that she can’t afford to lose seizure control as she needs to drive for her work. She tells Alyssa that 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. She says that, if Millie were pregnant, then whatever she 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 could be to gradually taper down the amount of valproate she was taking and gradually introduce an alternative anti-epileptic medication such as levetiracetam. If she chose to change medication, she may need to stop driving temporarily.

Through the specialist review and second ARAF check, Millie's team will assess whether Valproate remains an option for her. Alyssa, her consultant neurologist and Dr Wright will support Millie to understand the evidence and information about the options. They will then help Millie to weigh up the risks and benefits of the options available, and decide what to do. This may be remaining on valproate or exchanging it – gradually and under medical supervision – for another medication.

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 Millie that there’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. 

Alyssa is well aware that untreated epilepsy can itself cause harm to both a woman and her unborn baby, so it wouldn’t necessarily be a straightforward decision for Millie. It would be crucial to carefully consider all the relevant, up-to-date, evidence-based information about the options available before supporting Millie to decide about what medication would be best for her specific circumstances. 

There’s a knock at the door and Alyssa’s colleague comes in with the pregnancy test for Millie.

Patient resources and support

Patient resources and support

Patient support groups

Anti-convulsant Syndrome support groups

INFACT/FACSA

This website hosts both:

OACS Charity

The Organisation for Anti-convulsant Syndrome charity is for those that have been touched by the effects of medications such as sodium valproate.

Valproate Victims UK

A membership organisation, Valproate Victims UK is for those affected by valproate in pregnancy.

Epilepsy patient support groups

Epilepsy Action

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. 

Epilepsy Society

A national charity, Epilepsy Society carries out epilepsy research and support. 

SUDEP Action

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.

SUDEP Action manages the Epilepsy Deaths Register and provides specialist support to bereaved families.

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
  • EpSMonis an award-winning app that helps people with epilepsy self-monitor in between visits to the doctor.

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Reports reviews and guidance

Reports, reviews and guidance

Reports and reviews

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