Depakote and Depakote ER

Depakote (divalproex sodium) and Depakote ER (divalproex sodium extended release) for migraine prevention: an introduction

Depakote is an anticonvulsant medication that is used for treating several illnesses and disorders. It has been approved for preventing migraines since 1996. Depakote, which first became available in the early 1982, is also approved by the U.S. Food and Drug Administration for treating bipolar disorder and seizures. Since 1998, the medication has been available as a less-costly generic, which is sold under the names divalproex sodium and valproic acid.

How Depakote works for the prophylactic treatment of migraine

It is unsure exactly how Depakote works for migraine prophylaxis or prevention. It appears to increase proteins in the brain that turn off brain chemicals that lead to migraines. It may also decrease the substances in the brain that are related to migraine symptoms.

Depakote’s effectiveness

All migraine sufferers react differently to each medication. During the clinical trials of Depakote, it was compared to an inactive placebo or sugar pill. Patients with migraines who took Depakote ER had half as many migraines in a four-week period as those who were given the placebo.

Forms of Depakote available

  • Depakote – Enteric-coated delayed-release tablets
  • Depakote Sprinkles – delayed-release capsules
  • Depakote ER – enteric-coated extended-release tablets
  • Depakene Syrup
  • Depacon Injection

Only Depakote and Depakote ER have been approved for preventing migraines.

Enteric-coated medications are covered with a material to prevent the medicine from being broken down by the stomach acids quickly and to prevent it from irritating the stomach lining. Delayed release forms of medications postpones the release of the drug until the medicine has passed through the stomach. Extended release formulations make the medication available over a longer period of time after the tablet has been swallowed. The Depakote Sprinkles can be sprinkled on soft food, such as applesauce, that doesn’t require chewing.

Most common side effects of Depakote and Depakote ER

  • Drowsiness or insomnia
  • Rash
  • Dizziness
  • Headache
  • Diarrhea or constipation
  • Heartburn
  • Changes in appetite
  • Weight changes
  • Back pain
  • Agitation or mood swings
  • Abnormal thinking
  • Memory loss
  • Tremor, uncontrollable shaking of a part of the body
  • Loss of coordination
  • Uncontrollable eye movements
  • Blurred or double vision
  • Tinnitus, ringing in the ears
  • Stuffed or runny nose
  • Sore throat
  • Alopecia, hair loss

Serious side effects

The Food and Drug Administration requires its strongest warning on Depakote. It is called a black-box warning, because the words are in bold and outlined by a black box. Depakote, it’s other formulations and other medications in its class, may lead to life-threatening liver toxicity. This usually occurs during the first six months of treatment and very young children, under age 2 are at a much higher risk of this serious liver problem. Symptoms of liver problems include weakness, uneasiness, fatigue, facial swelling, lack of appetite and vomiting. Before beginning treatment and regularly during treatment, liver function tests should be performed when taking Depakote and similar therapies. Depakote should be prescribed with caution in people who have a history of liver disease. People who are taking more than one anti-convulsant drug, children, people with congenital metabolic disorders, those with severe seizure disorders who also have mental retardation and those with brain disease may be at higher risk.

Cases of life-threatening pancreatitis have been reported in children and adults on Depakote. Some cases occurred soon after the drug was started, while others happened after years of use. Patients and their caregivers should seek immediate medical attention if these symptoms are noticed: abdominal pain, nausea, vomiting and lack of appetite.

Who should not take Depakote for migraine prevention

Depakote should not be taken by women who are pregnant or who may become pregnant because it can cause serious deformities. People with known liver disease or liver dysfunction shouldn’t take Depakote. People who have hypersensitivity to Depakote or any of its ingredients should not be prescribed it. Also those with urea cycle disorders should not take it.



As always, the best source for advice on preventing your migraines is your own migraine specialist. These medication descriptions are provided only for informational purposes. You should begin no medication regimen without first checking with your physician. Again, this information should in no way substitute or be mistaken for medical advice.

Written by: Otesa Miles | Last review date: November 2010
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