Valproate in women and girls who could get pregnant

Sodium valproate is a medication developed in the 1970s for the treatment of epilepsy. Since the 1990s it has also been used to treat bipolar disorder.

Forms of Valproate, also called Sodium Valproate, are Valproic Acid (Semisodium Valproate) are found in the medicines called Epilim and Depakote.

Valproate is an effective medicine for the treatment of Bipolar Disorder. 

However, if it is taken during pregnancy it can harm an unborn baby.

Valproate is much more likely to harm a baby than other medicines used for Bipolar Disorder ⁽¹⁾.

The higher the dose of Valproate, the higher the risk of harm⁽²⁾.

Pregnancy does not protect you from becoming unwell with Bipolar Disorder. The risk of a relapse is high during pregnancy - and very high in the first few weeks after having a baby. The risk is particularly high if you aren’t taking medication ⁽³⁾. 

If you have a diagnosis of Bipolar Disorder, you also more likely to have a Postpartum Psychosis ⁽³⁾. This is a severe mental illness which usually starts in the first few weeks after birth (see our leaflet about Postpartum Psychosis for more information).

If you have Bipolar Disorder and want to plan a pregnancy, or are already pregnant, do see a psychiatrist - ideally a specialist Perinatal Psychiatrist - for specialist advice, care and treatment. This will help you to stay well during pregnancy, and after the birth.

In women prescribed Valproate for epilepsy, Valproate has been shown to increase the rate of polycystic ovarian syndrome ⁽⁴⁾. This can make it more difficult to become pregnant. Also, this effect can persist after stopping Valproate.

Valproate can harm babies in the womb. It can then cause problems with development and learning throughout a child’s life.  

• In women with no illness and taking no medication, around 2-3 babies in every 100 will have a birth defect.
• In women who take Valproate whilst they are pregnant, around 10 babies in every hundred (10%) will have a birth defect ^(5,6). These birth defects include:

-spina bifida (where the bones of the spine do not join up properly).

-cleft lip and cleft palate (where the upper lip or bones in the face are split).

-abnormalities of the limbs, heart, kidney, urinary tract and sexual organs.

• In women who have taken Valproate whilst they were pregnant, 30-40 children in every hundred (30-40%) are likely to have developmental difficulties. This can include delay in learning to walk and talk, lower intelligence, poor speech and language skills and memory problems ^(7,8).
• Children whose mothers were taking Valproate when they were in the womb are more likely to have Autism and Autistic Spectrum Disorders ^(8,9). They may also be more likely to have Attention Deficit Hyperactivity Disorder (ADHD) ⁽¹⁰⁾.

Folic acid is recommended for all women planning pregnancy to help protect against Spina Bifida. However, even in high doses, it does not prevent any of the increased risk of birth defects ⁽¹¹⁾. High dose folic acid can also interfere with Valproate’s effectiveness in Bipolar Disorder ⁽¹²⁾.

There are other medicines that can be used to treat Bipolar Disorder that are much less likely to harm the baby. These should be prescribed for any woman who has the potential to get pregnant, even if she is not planning a pregnancy. The National Institute for Health and Care Excellence (NICE) ⁽¹³⁾ the Scottish Intercollegiate Guidelines Network (SIGN) ⁽¹⁴⁾, and the British Association of Psychopharmacology ⁽¹⁾ say that Valproate should not be prescribed to treat Bipolar Disorder in girls or women who are able to become pregnant.

The European Medicines Agency (15) and the Medicines and Healthcare products Regulatory Agency (UK) (16) has recommended that, if you are able to have children, Valproate must not be used unless: 

• You have had a conversation with the specialist who is going to prescribe the Valproate about your chances of becoming pregnant and the need for effective contraception throughout treatment.
• You should have a pregnancy test before starting treatment with Valproate.
• You must have a review of the Valproate treatment at least once a year by a specialist. 
• At each yearly review, you and the specialist will discuss the risks to an unborn baby.
• At the start of treatment - and at each yearly review – you and the specialist must sign a risk acknowledgment form. This shows that everyone understands the risks of becoming pregnant whilst taking Valproate.

In rare cases, you might decide that, even with all the problems, the best plan for you is to continue taking Valproate. This could be because:

• You have no plans to become pregnant.
• Other treatments have not been helpful.
• You are extremely unlikely to get pregnant – e.g. because you have had a sterilisation.

If you, your family and your doctor, considering the guidance and the risk to babies, decide that Valproate is the best option to treat your Bipolar illness, then:

• You and your doctor need to be clear about the serious risks to the baby if you were to become pregnant.
• You must have written information about these risks.
• You must be sure that there is no chance of an unplanned pregnancy. If this involves using contraception, then it should be one of the more reliable forms of contraception such as an implant, coil or sterilisation.

If you could become pregnant, and you are taking Valproate to treat Bipolar Disorder, it is important that you do not stop the medication suddenly.  This will increase your risk of becoming unwell. Make an appointment with the doctor who prescribes your Valproate. Together you can think about what medicine might be safer for you to take to treat your Bipolar illness.

If you are taking Valproate for Bipolar Disorder and you think you might be pregnant, don’t stop your medication suddenly. Ask your psychiatrist, or GP, to refer you to a Perinatal Psychiatrist if there is one in your area. If not, you should see your psychiatrist, or ask your GP to refer you to one. Together you can decide what medication would be safest for you to take for the rest of your pregnancy, and after you have your baby.  

Valproate Guide for patients - Valproate pregnancy prevention programme (May 2018). www.medicines.org.uk/emc/rmm/756/Document 

Medicines and Healthcare products Regulatory Agency (MHRA) Guidance Valproate use by women and girls – a toolkit including information for professionals, a patient booklet and patient card. www.gov.uk/guidance/valproate-use-by-women-and-girls 

National Centre for Mental Health, Bipolar UK & Action on Postpartum Psychosis: Bipolar disorder, pregnancy and childbirth Information for women, partners and families www.app-network.org/wp-content/uploads/2014/09/Bipolar-Pregnancy-Childbirth-Booklet.pdf 

1. McAllister-Williams RH, Baldwin DS, Cantwell R, Easter A, Gilvarry E, Glover V  et al. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum.  J Psychopharmacol. 2017; 31: 519-552.
2. Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Perucca E et al. Dose-dependent teratogenicity of valproate in mono- and polytherapy: an observational study. Neurology. 2015 ;85 :866-72.
3. Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJ ,Kushner SA, Bergink V. Risk of Postpartum Relapse in Bipolar Disorder and Postpartum Psychosis: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2016; 173:117-27.
4. Svalheim S, Sveberg L, Mochol M, Tauboll E.  Interactions between antiepileptic drugs and hormones. Seizure. 2015; 28: 12–17.
5. Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: A systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008; 81:1–13.
6. Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK et al.  Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med. 2010; 362: 2185–2193.
7. Bromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ et al. (2014) Treatment for epilepsy in pregnancy: Neurodevelopmental outcomes in the child. Cochrane Database Syst Rev Issue 10. Article No.: CD010236

The ‘Building Capacity, Psychiatry Leadership in Perinatal Mental Health Services’ project: commissioned by NHS England in partnership with Health Education England and delivered by the Royal College of Psychiatrists.

• Expert review: Dr Gillian Strachan, Dr Sarah Jones and Dr Lucinda Green
• Service users and carers: Action on Postpartum Psychosis
• Series Editor: Dr Phil Timms 
• Series Manager: Thomas Kennedy