In view of the news that have appeared in different media and the questions we receive from our patients, our Epilepsy Program would like to clarify some of the risks of valproic acid (Depakine®) when used during pregnancy.
What is valproic acid?
Valproic acid is an antiepileptic drug that has been widely used since the 1970s throughout the world. It is also effective in other neurological and psychiatric conditions, such as migraine and bipolar disorder. In a 2013 Spanish study, it was the most widely used drug in generalized epilepsies and the third in adult focal epilepsies. These utilization data are similar to those of other European and American countries. However, some studies show that its use is decreasing slightly in recent years.
What problems can valproic acid cause in pregnancy?
The relationship between the possible occurrence of malformations in the newborn with the intake of valproic acid during pregnancy has been known since the 1980s. These malformations can be of various kinds (neural tube defects, facial anomalies, congenital heart disease, etc.), and are related to the dose of the drug. With doses of less than 700 mg of valproic acid per day, and taken without being associated with other drugs (in monotherapy), the frequency of these malformations in published studies is similar to that of children born to women taking other antiepileptic drugs.
Since 2013 several scientific publications, mainly from Scandinavian countries, have linked valproic acid treatment during pregnancy with cognitive problems and increased frequency of autism spectrum disorders. This relationship was not known before 2013. According to these publications, the alterations can appear with all doses of the drug, being more probable and severe with high doses. However, these studies do not specifically analyze what happens when low or very low doses are administered.
Can it cause problems if taken outside pregnancy?
Taking valproic acid outside of pregnancy has been shown to be safe, and is not associated with an increased likelihood of problems in future pregnancies. Similarly, it has been shown that taking this drug by the father does not carry any risk for the pregnancy.
Why is valproic acid still used?
Despite the risks of taking it during pregnancy, valproic acid is still widely used for the treatment of epilepsy. This is because it is the most effective drug for numerous types of epilepsy, such as juvenile myoclonic epilepsy or absence epilepsy. Despite constant research and development of new drugs, recent studies have shown that a significant proportion of patients have their seizures controlled only with valproic acid.
In addition, it has been observed that in some patients its withdrawal during pregnancy has produced status epilepticus, a complication of epilepsy that consists of a very prolonged epileptic seizure, which puts the patient’s life at risk and can also cause oxygen deprivation in the fetus and thus permanent neurological damage.
Valproic acid is also indispensable for seizure control in some patients with refractory focal epilepsy, especially when combined with lamotrigine and other drugs. In addition, in other severe epilepsies of pediatric age, such as Lennox-Gastaut syndrome or Dravet syndrome, valproic acid is the cornerstone of treatment.
What can we do to avoid these problems?
In women of childbearing age, valproic acid should only be used in those situations in which there are no other safer effective treatments in pregnancy, or these have previously failed to control the patient’s seizures. In this situation, the patient should be informed and be aware of the benefits and risks. Currently there are informative documents from different medical societies and from the manufacturer of valproic acid that can be administered to the patient in the office. In addition, it is always preferable to use the drug alone (since the combination with other drugs increases the risk of malformations) and with the minimum effective dose.
Please note that this general information is not a substitute for information provided by your physician.
If you have any further questions, please contact us and the Epilepsy Program Team.
