Sodium valproate: Risk of neurodevelopmental delay in children following maternal use
- Medicines and Healthcare products Regulatory Agency
- 14 November 2013
- Therapeutic area:
- Neurology, Obstetrics, gynaecology and fertility, and Psychiatry
Not for use in pregnancy unless there is no effective alternative.
Article date: November 2013
This article has been superseded. Please see the article published in February 2016 for the latest advice
Sodium valproate (brand name Epilim) has been authorised since 1973 for the treatment of epilepsy. Depakote is the brand of sodium valproate authorised for the treatment of the manic phase of bipolar disorder.
Risks during pregnancy
It is well established that women who take antiepileptics during pregnancy have a higher risk of having a child with a birth defect than do women in the general population—this risk is estimated to be 2 to 3 times higher. This risk is further increased if a woman takes more than one antiepileptic medicine during pregnancy.
The use of sodium valproate is associated with a greater risk of some types of these malformations (in particular neural tube defects) than with some other antiepileptic drugs. This risk is clearly reflected in the product information provided for patients and prescribers.
In recent years, results of further studies have emerged that indicate a risk of long term neurodevelopmental effects after in uteroexposure to sodium valproate. These studies have highlighted that in some children the effects appear to persist and manifest as a range of neurodevelopmental abnormalities and autism spectrum disorders. These emerging data also suggest that these risks may be independent of maternal confounders.1 2 3 4
The most recent publications on an association between fetal valproate exposure and neurodevelopmental delay or autism spectrum disorder have prompted a re-evaluation of the balance of benefits and risks of this medicine. The review is now underway in Europe, and further updates will be issued in due course. In the meantime, healthcare professionals are reminded of the following advice:
Advice for healthcare professionals:
- sodium valproate should not be used during pregnancy and in women of childbearing potential unless clearly necessary
- women of childbearing potential should not start treatment with sodium valproate without specialist neurological or psychiatric advice as appropriate depending on the indication
- adequate counselling should be made available to all women of childbearing potential to weigh the risk of teratogenic and neurodevelopmental effects against the benefits of treatment
- in the bipolar disorders indication, cessation of sodium valproate treatment should be considered if there is an effective alternative
- if sodium valproate is to be used during pregnancy, the lowest effective dose is recommended divided over the day or controlled-release tablets to avoid rapid peaks in plasma level
- folate supplementation should be started before pregnancy as appropriate
- specialist prenatal monitoring should be instigated to detect possible occurrence of neural tube defects or other malformations when valproate has been used
Article citation: Drug Safety Update volume 7 issue 4, November 2013: A2.
Published: 14 November 2013