What are the risks and benefits of using divalproex sodium (Depakote) for treating seizures? Are there people who should avoid this drug?
Martha J. Morrell, M.D., Fellow of the American Academy of Neurology, is a clinical professor of neurology at Stanford University in CA and a specialist in epilepsy care. Dr. Morrell also serves as the chief medical officer of NeuroPace, Inc., a company that focuses on the treatment of neurologic disorders with responsive brain stimulation.
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Q What are the risks and benefits of using divalproex sodium (Depakote) for treating seizures? Are there people who should avoid this drug?
DR. MARTHA J. MORRELL RESPONDS:
A Divalproex sodium (Depakote, Depakote ER) is an effective and well-tolerated antiepileptic drug (AED) for many people with seizures. It has been available in the United States since 1983 for the treatment of complex partial, myoclonic, and absence seizures. During a complex partial seizure, an individual loses awareness; myoclonic seizures are brief, shock-like jerks of a muscle or group of muscles; and absence seizures are characterized by lapses of awareness that begin and end suddenly, lasting only a few seconds.
Many doctors also use the medication for generalized tonic clonic seizures, which involve the entire body. Divalproex sodium is a particularly useful medication because it is effective for so many types of seizures.
However, as with any medication, side effects are possible. Rare but potentially serious side effects include inflammation of the pancreas (pancreatitis) and liver toxicity. More commonly, divalproex sodium has the potential to cause weight gain, disturbances in reproductive health, and, if used during pregnancy, birth defects and neurodevelopmental delay (the omission or arrest of a stage of early development). Divalproex sodium can slow the metabolism of carbohydrates and increase levels of the hormone insulin and testosterone. As a result, women may develop polycystic ovaries and experience irregular menstrual cycles. In turn, these effects can cause weight gain, increased facial or body hair, thinning of scalp hair, and acne. Let your doctor know if any of these symptoms occur.
Divalproex sodium is also known to increase the risks for birth defects, including defects of the brain and spinal cord. In the general population, approximately 3 percent of babies are born with birth defects. This rate is even higher for infants exposed to divalproex sodium during pregnancy. According to a North American registry of pregnancies in women taking AEDs, the risk of birth defects in infants born to mothers who had taken valproate (very similar to divalproex sodium) is 9.3 percent. A larger European Registry found the risk for birth defects to be 5.6 percent for women taking less than 700 mg a day of divalproex sodium, and 24 percent with doses of 1500 mg or more a day.
In addition, an ongoing study in the United States and United Kingdom—the Neurodevelopmental Effects of Antiepileptic Drugs, or NEAD, study—indicates that children exposed to divalproex sodium during pregnancy have lower IQ scores, poorer motor functioning, and may also have poorer social skills. Higher doses of divalproex sodium appear to be associated with higher risks for these developmental problems.
Based on these safety concerns, divalproex sodium is generally not considered to be the AED of choice for women in their reproductive years. Your doctor may suggest other AEDs based on your seizure type. However, for some patients, divalproex sodium may be the only medication able to control seizures. In this situation, divalproex sodium is used at the lowest possible dose to control seizures. If a pregnancy occurs, a special type of ultrasound will be performed in order to look at the baby's brain and spinal cord. Many doctors recommend that women taking divalproex sodium also take folic acid at doses of 0.4 mg to 5 mg a day, although it is not known whether this effectively protects against birth defects.
Seizures also cause a risk to the fetus, so for most women with epilepsy, not taking an AED during pregnancy is not a safe option. If you are planning a pregnancy, speak to your doctor about the best medication options. If you find that you are pregnant and taking divalproex sodium, do not stop your medication. Meet with your doctor to discuss the best pregnancy management.