Valproate for Migraine - Contraindicated Due to Decreased IQ Scores in Exposed Children
Vital safety information for pregnant women who are using or considering using valproate medications for Migraine prevention was released by the FDA today. The results of studies have now provided enough strong evidence that exposure to valproate medications while the mother is pregnant results in decreased IQ scores. This has resulted in the FDA changing the pregnancy category of these drugs from D to X, which means that the risk of use during pregnancy outweighs any possible benefits.
Valproate medications include:
- Depakote CP
- Depakote ER
- Depakote Sprinkles
- divalproex sodium
- valproate sodium
- valproic acid
Here's the full statement issued by the FDA today:
The U.S. Food and Drug Administration (FDA) is advising health care professionals and women that the anti-seizure medication valproate sodium and related products, valproic acid and divalproex sodium, are contraindicated and should not be taken by pregnant women for the prevention of migraine headaches. Based on information from a recent study, there is evidence that these medications can cause decreased IQ scores in children whose mothers took them while pregnant.1 Stronger warnings about use during pregnancy will be added to the drug labels, and valproate’s pregnancy category for migraine use will be changed from "D" (the potential benefit of the drug in pregnant women may be acceptable despite its potential risks) to "X" (the risk of use in pregnant women clearly outweighs any possible benefit of the drug).
With regard to valproate use in pregnant women with epilepsy or bipolar disorder, valproate products should only be prescribed if other medications are not effective in treating the condition or are otherwise unacceptable. Valproate products will remain in pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder.
With regard to women of childbearing age who are not pregnant, valproate should not be taken for any condition unless the drug is essential to the management of the woman's medical condition. All non-pregnant women of childbearing age taking valproate products should use effective birth control.
Valproate products include: valproate sodium (Depacon), divalproex sodium (Depakote, Depakote CP, and Depakote ER), valproic acid (Depakene and Stavzor), and their generics.
This alert is based on the final results of the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study showing that children exposed to valproate products while their mothers were pregnant had decreased IQs at age 6 compared to children exposed to other anti-epileptic drugs (see Data Summary).1 The difference in average IQ between the children who had been exposed to valproate and the children who had been exposed to other antiepileptic drugs varied between 8 and 11 points depending on the drug to which valproate was compared.
FDA previously communicated initial findings about this risk in a June 2011 Drug Safety Communication. At that time, FDA also worked with valproate manufacturers to revise the drug labels after interim results from the NEAD study showed lower cognitive test scores at age 3 in children exposed to valproate compared to children exposed to other antiepileptic drugs.2
Women who are pregnant and taking a valproate medication should not stop their medication but should talk to their health care professionals immediately. Stopping valproate treatment suddenly can cause serious and life-threatening medical problems to the woman or her baby.
It is not known whether there is a specific time period during pregnancy when valproate exposure can result in negative cognitive effects. Similarly, there is no known time during pregnancy in which exposure may be considered to have less risk for decreased IQ in children. Because the women in the NEAD study were exposed to antiepileptic drugs throughout pregnancy, whether the risk for decreased IQ was related to a particular time period during pregnancy could not be assessed.
FDA is working with manufacturers to change the drug labels for valproate products with this updated risk information. FDA continues to evaluate information about the potential risks of valproate use during pregnancy and will update the public as more information becomes available.
Pregnancy Category X means that studies in animals or humans have shown positive evidence of fetal risk, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefits. Category D means there is positive evidence of risk to a baby based on data from studies or other experience in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.
- Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurology 2013; 12 (3): 244-252.
- Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009; 360:1597-605.
- IMS, Total Patient Tracker (TPT). July 2009 – June 2012. Extracted February 2013.
- Encuity Research, LLC., Physician Drug & Diagnosis Audit (PDDA) with Pain Panel. 2012. Extracted March 2013.
Summary and comments:
This is vital information for women in childbearing years. If you are pregnant and taking any valproate medication, please contact your physician immediately. If you are not pregnant and taking any of these medications, FDA stresses the importance of effective birth control.
If you are taking valproate medications, do not discontinue them without the guidance of your doctor. Abruptly discontinuing these medications can be dangerous.
If you're taking these medications and could become pregnant, please make an appointment to discuss this issue with your doctor.
Drug Safety Announcement. "FDA Drug Safety Communication: Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children." ood and Drug Administration. May 6, 2013.
The American Society of Health-System Pharmacists. "Valproic Acid." Medline Plus. May 2, 2013. "
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