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Depakote® (Divalproex Sodium)

Depakote® (divalproex sodium) is a valproate (anti-epiletic drug) that is indicated for the prevention of migraine in adults. It is taken by mouth as preventative therapy to reduce migraine frequency. Those with frequent migraine attacks or migraine who do not respond to acute treatment should consider preventive medications. There is no evidence that Depakote is useful in the acute treatment of migraine.

Depakote comes in 3 formulations: tablets, extended relief and sprinkles.

What are the ingredients in Depakote?

The active ingredient in Depakote is divalproex sodium.

How does Depakote work?

The precise way Depakote works to prevent migraine is unknown. It dissolves in the gastrointestinal tract, and when it reaches the brain is thought to block brain chemicals that contribute to the development of migraine symptoms.

What are the possible side effects of Depakote?

Many clinical trials evaluated the safety and efficacy of Depakote. The most common side effects experienced by those taking Depakote include:

  • Bleeding problems
  • High ammonia levels in your blood
  • Low body temperature (hypothermia)
  • Allergic reactions including rashes, hives and swelling
  • Feeling weak, drowsy, or tired
  • Stomach pain, nausea, vomiting and diarrhea
  • Vision problems
  • Increased appetite and weight gain
  • Dizziness

Pancreatitis is also potential serious side effect. According to the black box warning, “Inflammation of your pancreas that can cause death. Call your healthcare provider right away if you have any of these symptoms: severe stomach pain that you may also feel in your back, nausea or vomiting that does not go away.”

This is not an exhaustive list of all potential side effects of Depakote. For more information, consult your doctor or healthcare provider. If you notice any new or worsening side effects when taking Depakote contact your doctor or healthcare provider immediately.

Things to note about Depakote

Depakote is taken by mouth with water or other liquids. Dosing depends on the form of the medication prescribed. Depakote and Depakote ER are the two formulations generally prescribed for preventing migraine. Depakote is taken twice a day. Depakote ER is taken once a day. Both are effective in reducing the frequency of migraine. The extended release tablets supply a steady stream of medication over 24 hours. Before starting Depakote talk with your doctor if you:

  • Have a history of hypersensitivity to divalproex sodium, valproic acid or sodium valproate
  • Drink alcohol
  • Have a history of liver problems
  • Have certain genetic conditions including urea cycle disorder or Alpers-Huttenlocher syndrome
  • Take aspirin
  • Take other migraine medications
  • Take antibiotics
  • Take anti-depressants
  • Have a history of depression or suicidal ideation
  • Are pregnant or planning to get pregnant. Depakote is not recommended during pregnancy as it causes birth defects.

Individuals with the above conditions should be monitored closely while taking any form of Depakote.

Dosing information

Depakote and Depakote ER tablets can be taken with or without food and should be swallowed whole. Do not open and sprinkle on food, chew, or crush the medication.

Depakote Sprinkle Capsules may be swallowed whole, or they may be opened and the contents may be sprinkled on a small amount of soft food, such as applesauce or pudding.

Take Depakote every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose.

Depakote: Depakote is taken twice a day in a divided dose for effectiveness in reducing the frequency of migraine. The recommended starting dose is 250 mg twice daily. Some patients may benefit from doses up to 1,000 mg/day. Depakote tablets come in 3 strengths:

  • 125 mg
  • 250 mg
  • 500 mg

Depakote ER: Depakote ER is intended for once-a-day oral administration. It comes in 2 strengths, 250 mg and 500 mg tablets. The recommended starting dose is 500 mg once daily for 1 week, increasing to 1000 mg once a day in the second week. The effective dose range for Depakote ER can be from 500-1000 mg/day. As with other valproate medications, a physician will guide the dose and titration rate, based on individual medical circumstances, and clinical outcomes. Longer intervals between dose adjustments can be used. However, if a lower dose is required than that available with Depakote ER, Depakote should be used instead.

Depakote Sprinkles: Depakote sprinkles are used less often for the treatment of migraine. However, for those who have difficulty swallowing pills, the sprinkles may be an option to discuss with your physician. The sprinkles come in 125 mg capsules. Drinking fluids are important when taking this medication. Dosage may need to be adjusted if you do not get enough fluids each day.

All formulations of Depakote should be stored at room temperature.

Do not suddenly stop taking Depakote without talking to your doctor, as serious complications can arise.

Keep track of when you have migraine attacks and when you take Depakote so you can monitor its effectiveness, and communicate with your doctor about how the medication is working for you.

Before taking any form of Depakote make sure to tell your doctor about all the medicines you take, including prescription and nonprescription, vitamins, and herbal supplements. Depakote and other medicines may impact each other, causing side effects.

Because Depakote can cause dizziness, weakness, and drowsiness, do not drive a car, use machinery, or do anything requiring you to be fully alert when taking this medication.

For additional details, read the full prescribing information of Depakote products.

Written by: Linda Saxl Minton | Last reviewed: November 2019
  1. Depakote prescribing information available at: Accessed 5/4/18.
  2. Depakote ER prescribing information available at: Accessed 5/4/18.
  3. Depakote Sprinkles prescribing information available at: Accessed 5/4/18.