Depakote (divalproex delayed-release [DR]) and Depakote ER (divalproex extended-release) are brand-name prescription medications. They’re approved by the Food and Drug Administration (FDA) to:

For these purposes, Depakote and Depakote ER are typically taken as long-term treatments.

Here are some fast facts about Depakote and Depakote ER:

  • Active ingredient: divalproex
  • Drug class: antiepileptic
  • Drug forms:
    • delayed-release (DR) oral tablets*
    • extended-release (ER) oral tablets†
    • DR sprinkle capsules‡

Like other drugs, Depakote and Depakote ER can cause side effects. Read on to learn about potential common, mild, and serious side effects. For a general overview of Depakote and Depakote ER, including details about the uses of each form, see this article.

* DR tablets have a coating that keeps the tablet from releasing the drug into your body until it has passed through your stomach.
† ER tablets release the drug slowly into your body over time.
‡ DR sprinkle capsules can be swallowed whole or opened so their contents can be sprinkled onto food.

Depakote and Depakote ER can cause certain adverse effects (side effects), some of which are more common than others. The side effects in the sections below are based on clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

These are just a few of the more common side effects reported by people who took Depakote and Depakote ER:

These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

* For more information about this side effect, see “Side effect specifics” below.

Side effects in younger adults vs. older adults

Compared with younger adults, adults ages 65 years and older may have a higher risk of certain side effects from Depakote and Depakote ER.

The side effects below were more common in older adults than in younger adults:

  • sleepiness
  • infection
  • accidental injury*
  • tremor† (uncontrollable shaking in a part of your body)

In addition, older adults may have certain health conditions that affect how their bodies respond to Depakote and Depakote ER. These include dementia (problems with thinking, memory, and communication), kidney problems, and liver problems. These conditions could raise their risk of side effects from the drug.

Due to these potential risks, older adults may be prescribed a lower starting dosage of Depakote or Depakote ER. (For more information on dosage, see this article.)

If you’re age 65 years or older, talk with your doctor before taking Depakote or Depakote ER. They can advise on the risks and benefits of taking the drug to treat your condition.

* This side effect was more common with Depakote DR tablets and Depakote ER tablets than with Depakote DR sprinkle capsules.
† For more information about this side effect, see “Side effect specifics” below.

Mild side effects can occur with Depakote and Depakote ER use. This list doesn’t include all possible mild side effects of the drug. For more information, you can refer to the prescribing information for Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

Mild side effects that have been reported with Depakote and Depakote ER include:

These side effects may be temporary, lasting a few days to weeks. However, if the side effects last longer than that, bother you, or become severe, be sure to talk with your doctor or pharmacist.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you develop a side effect while taking Depakote or Depakote ER and want to tell the FDA about it, visit MedWatch.

* This side effect was more common with Depakote DR tablets and Depakote ER tablets than with Depakote DR sprinkle capsules.
† For more information about this side effect, see the “Depakote and Depakote ER and weight gain” section below.
‡ To learn more about this side effect, see “Side effect specifics” below.

Depakote and Depakote ER may cause serious side effects. The list below may not include all possible serious side effects of the drug. For more information, you can refer to the prescribing information for Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

If you develop serious side effects while taking Depakote or Depakote ER, call your doctor right away. If the side effects seem life threatening or you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Serious side effects that have been reported and their symptoms include:

* Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules have a boxed warning for this side effect. This is the most serious warning from the Food and Drug Administration (FDA).
† To learn more about this side effect, see the “Side effect specifics” section below.
‡ For more information, see “Pregnancy and breastfeeding while taking Depakote and Depakote ER in the “Precautions for Depakote and Depakote ER” section below.
§ An allergic reaction is possible after taking Depakote and Depakote ER. However, it’s not clear whether this side effect occurred in clinical trials.

Suicide prevention

If you know someone at immediate risk of self-harm, suicide, or hurting another person:

  • Ask the tough question: “Are you considering suicide?”
  • Listen to the person without judgment.
  • Call 911 or the local emergency number, or text TALK to 741741 to communicate with a trained crisis counselor.
  • Stay with the person until professional help arrives.
  • Try to remove any weapons, medications, or other potentially harmful objects.

If you or someone you know is having thoughts of suicide, a prevention hotline can help. The National Suicide Prevention Lifeline is available 24 hours per day at 800-273-8255. During a crisis, people who are hard of hearing can use their preferred relay service or dial 711 then 800-273-8255.

Click here for more links and local resources.

Long-term side effects

Depakote and Depakote ER may cause certain long-term side effects. For example, there have been reports of pancreatitis* (swelling of the pancreas) after long-term use of the drugs.

However, the length of side effects from Depakote and Depakote ER can vary from person to person.

If you’re concerned about long-term side effects with Depakote or Depakote ER, talk with your doctor.

* Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules have a boxed warning for this side effect. This is the most serious warning from the Food and Drug Administration (FDA). To learn more, see the “Side effect specifics” section below.

Weight gain is possible with Depakote and Depakote ER. This was a common side effect in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

Also, keep in mind that increased appetite is another possible side effect of Depakote and Depakote ER. And having an increased appetite could lead to weight gain over time.

If you’re concerned about weight gain while taking Depakote or Depakote ER, talk with your doctor. They can suggest healthy ways to manage or maintain your weight while taking the drug.

Learn more about some of the side effects that Depakote and Depakote ER may cause.

Hair loss

Hair loss is possible with Depakote and Depakote ER. This side effect was common in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

Clinical trials also suggest that the risk of hair loss with Depakote may be greater at higher doses of the drug.

What you can do

If you’re concerned about hair loss with Depakote or Depakote ER, talk with your doctor. They can advise if a lower dose of the drug can be prescribed to treat your condition. Or they may recommend a different drug that doesn’t cause this side effect.

Tremor

Some people may experience tremor (uncontrollable shaking in a part of your body) with Depakote or Depakote ER. Tremor refers to uncontrollable shaking that affects different parts of the body, such as the head, arms, and hands.

Tremor was a common side effect in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules. The side effect was more common in adults 65 years and older than in younger adults.

What you can do

If you develop a tremor while taking Depakote or Depakote ER, talk with your doctor. They can suggest ways to ease your symptoms. If your tremor is bothersome, your doctor may prescribe a different treatment for you instead.

Pancreatitis

Depakote and Depakote ER have a boxed warning for the risk of pancreatitis (swelling of the pancreas). A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

Pancreatitis wasn’t reported in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules. However, this side effect has been reported since the drugs became available for use.

Symptoms of pancreatitis can include:

  • fever
  • loss of appetite
  • sudden pain in the center of your abdomen
  • digestive problems such as diarrhea, nausea, and vomiting

In rare cases, pancreatitis from Depakote and Depakote ER may lead to serious, life threatening bleeding.

What you can do

Tell your doctor right away if you have symptoms of pancreatitis while taking Depakote or Depakote ER. They’ll likely switch you to a different treatment for your condition. If you have pancreatitis, they may prescribe medications to treat it.

Liver damage

Taking Depakote or Depakote ER may cause liver damage. In fact, Depakote and Depakote ER have a boxed warning for this risk. A boxed warning is the most serious warning from the FDA.

Liver damage wasn’t reported as a side effect in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules. However, liver damage has been reported since the drugs became available for use. Rarely, serious liver damage from Depakote and Depakote ER may be fatal.

Symptoms of liver damage while taking Depakote and Depakote ER include:

The risk of this side effect is highest in the first 6 months after you start taking Depakote or Depakote ER.* People with mitochondrial disorders are also at a higher risk of liver damage with Depakote and Depakote ER. (Mitochondrial disorders are a group of genetic conditions that prevent mitochondria from functioning as well as they should in cells.)

* The risk of liver damage with Depakote and Depakote ER is known to be highest in children ages 2 years and younger. Depakote and Depakote ER aren’t approved for use in children of this age, however.

What you can do

Before starting treatment with Depakote or Depakote ER, be sure your doctor knows about all your health conditions. They can advise if it’s safe for you to take the drug based on your health history.

Your doctor will likely give you blood tests to check your liver function before you start taking Depakote or Depakote ER. They may continue to monitor your liver function during your treatment.

Watch for symptoms of liver damage while taking Depakote or Depakote ER. Your doctor will monitor you for liver side effects as well. If you have symptoms of liver damage from Depakote or Depakote ER, tell your doctor right away. They’ll likely have you stop taking the drug.

Allergic reaction

As with most drugs, Depakote and Depakote ER can cause an allergic reaction in some people. However, it’s not clear whether this side effect occurred in clinical trials of Depakote DR tablets, Depakote ER tablets, and Depakote DR sprinkle capsules.

Symptoms can be mild or serious and can include:

  • skin rash
  • itching
  • flushing
  • swelling under your skin, typically in your eyelids, lips, feet, or hands
  • swelling of your mouth, tongue, or throat, which can make it hard to breathe

What you can do

For mild symptoms of an allergic reaction, call your doctor right away. They may recommend ways to ease your symptoms and determine whether you should keep taking Depakote or Depakote ER. However, if your symptoms are serious and you think you’re having a medical emergency, immediately call 911 or your local emergency number.

Depakote and Depakote ER aren’t known to cause withdrawal side effects. Withdrawal side effects happen when you stop taking a drug your body has become dependent on.

But it’s possible that stopping Depakote or Depakote ER could worsen symptoms of the condition you’re taking the drug to treat. For this reason, it’s important to talk with your doctor before you stop taking Depakote or Depakote ER.

If your doctor recommends you stop taking Depakote or Depakote ER, they’ll advise you how to do so. They may switch you to a different medication to decrease the risk of your condition worsening.

Depakote and Depakote ER may cause several side effects. Here are some frequently asked questions about the drug’s side effects and their answers.

Can taking too much Depakote or Depakote ER cause overdose symptoms?

Yes, taking too much Depakote or Depakote ER may cause overdose symptoms.

Examples of symptoms that have been reported with overdose include:

In rare cases, overdose from Depakote or Depakote ER may be fatal.

To avoid overdose, it’s important that you take Depakote or Depakote ER exactly as your doctor advises you to. If you have symptoms of overdose while taking the drug, tell your doctor right away. They may need to adjust your dosage. (For more information on dosage, see this article.)

Does Depakote or Depakote ER cause sexual side effects?

Yes, it’s possible for Depakote or Depakote ER to cause sexual side effects. These weren’t reported in clinical trials of Depakote DR tablets, Depakote ER tablets, or Depakote DR sprinkle capsules. However, there have been reports of sexual side effects after the drugs became available for use.

Specifically, erectile dysfunction has been reported with Depakote and Depakote ER. However, it isn’t known if Depakote or Depakote ER affects libido (sex drive).

Tell your doctor if you have sexual side effects while you’re taking Depakote and Depakote ER. They may prescribe a different treatment for your condition that doesn’t cause these side effects.

How do the side effects of the 250-milligram (mg) and 500-mg Depakote and Depakote ER tablets compare?

The side effects of Depakote and Depakote ER are expected to be the same regardless of the dose you’re prescribed.

However, in general, your risk of side effects from Depakote may be greater with higher doses of the drug.

If you’re concerned about your risk of side effects with your dosage of Depakote or Depakote ER, talk with your doctor. (For more information on dosage, see this article.)

What are the side effects when Depakote or Depakote ER is used off-label?

The side effects of Depakote and Depakote ER are expected to be the same regardless of the condition the drug is used to treat.

Depakote and Depakote ER are FDA-approved for the following purposes in certain situations:

Depakote and Depakote ER may also be used off-label for other conditions, such as anxiety and schizophrenia. Off-label drug use is when a doctor prescribes a drug for a purpose other than what it’s been approved for by the Food and Drug Administration (FDA).

Depakote and Depakote ER’s active ingredient (divalproex) works the same way in the body no matter which condition the drugs are used to treat. So, the side effects of Depakote and Depakote ER are expected to be the same.

If you have questions about what side effects to expect with Depakote or Depakote ER, talk with your doctor.

Is tardive dyskinesia a side effect of Depakote and Depakote ER?

Yes, in rare cases, Depakote and Depakote ER may cause tardive dyskinesia.

Tardive dyskinesia is a condition that causes uncontrolled muscle movements. These movements usually affect the face and include symptoms such as frowning, sticking out the tongue, lip smacking, and excessively blinking.

Tardive dyskinesia was a rare side effect reported in clinical trials of Depakote DR tablets and Depakote ER tablets. However, this side effect was not reported in clinical trials of Depakote DR sprinkle capsules.

If you have symptoms of tardive dyskinesia while taking Depakote and Depakote ER, talk with your doctor. They may prescribe a drug to treat your symptoms. Or they may prescribe you a different drug that doesn’t cause this side effect.

Do Depakote and Depakote ER cause hallucinations?

Rarely, Depakote and Depakote ER may cause hallucinations (seeing or hearing things that aren’t really there).

Hallucinations were a rare side effect reported in clinical trials of Depakote DR tablets and Depakote ER tablets. They weren’t reported in clinical trials of Depakote DR sprinkle capsules.

If you’re concerned about hallucinations with Depakote or Depakote ER, talk with your doctor.

What are the side effects of Depakote and Depakote ER in females?

The side effects of Depakote and Depakote ER are generally expected to be the same for females* and males.*

However, females taking Depakote or Depakote ER during pregnancy may experience side effects. For details, see “Pregnancy and breastfeeding while taking Depakote and Depakote ER” in the “Precautions for Depakote and Depakote ER” section below.

If you have questions about the risk of certain side effects from Depakote or Depakote ER, talk with your doctor.

* Sex and gender exist on spectrums. Use of the terms “female” and “male” in this article refers to sex assigned at birth.

Below is important information about precautions for Depakote and Depakote ER.

Boxed warnings

This drug has the following boxed warnings, which are serious warnings from the Food and Drug Administration (FDA).

  • Pancreatitis. To learn more, see the “Side effect specifics” section above.
  • Harm to a fetus. For more information, see “Pregnancy and breastfeeding while taking Depakote and Depakote ER” below.
  • Liver damage. For details, see the “Side effect specifics” section above.

Other precautions

Be sure to talk with your doctor about your health history before you take Depakote or Depakote ER. These drugs may not be the right treatment for you if you have certain medical conditions or other factors that affect your health. The conditions and factors to consider include:

Mitochondrial disorder. Before taking Depakote or Depakote ER, tell your doctor if you have a mitochondrial disorder. These are genetic conditions that prevent mitochondria from functioning as they should in cells. Having a mitochondrial disorder can raise your risk of liver damage with Depakote or Depakote ER. If you have this condition, your doctor may prescribe you another drug.

Problems with digestion. Tell your doctor about any digestive problems you have before starting treatment with Depakote or Depakote ER. This includes having had a previous ileostomy or colostomy. These factors may cause the drug to move through your digestive system without breaking down entirely in your body. If this happens, you may notice pieces of the capsules or tablet in your stool. And this could mean your body isn’t absorbing enough of the drug to treat your condition effectively. If you have certain problems with digestion, your doctor may prescribe another treatment.

Urea cycle disorder. Before taking Depakote or Depakote ER, tell your doctor if you have urea cycle disorder. Urea cycle disorder can increase the level of ammonia in your blood when taken with Depakote or Depakote ER. If you have this condition, tell your doctor before taking the drug.

Allergic reaction. If you’ve had an allergic reaction to Depakote, Depakote ER, or any of its ingredients, your doctor will likely not prescribe you these drugs. Ask your doctor what other medications may be better options for you. (For more information, see the “Side effect specifics” section above.)

Alcohol use with Depakote and Depakote ER

There is no known interaction between alcohol and Depakote or Depakote ER.

However, your doctor may recommend you avoid alcohol while taking these drugs. This is because alcohol, Depakote, and Depakote ER can cause sleepiness and dizziness on their own. So, drinking alcohol while taking Depakote or Depakote ER may worsen these side effects.

If you drink alcohol, talk with your doctor before taking Depakote or Depakote ER. They can recommend whether how much alcohol, if any, is safe for you to drink while taking the drug.

Pregnancy and breastfeeding while taking Depakote and Depakote ER

Below is information about taking Depakote and Depakote ER during pregnancy and breastfeeding.

Pregnancy

It likely isn’t safe to take Depakote or Depakote ER while pregnant. If taken during pregnancy, the drugs may cause problems with fetal development (commonly known as “birth defects”). Children exposed to these drugs during fetal development may also have lower IQ scores.

For these reasons, Depakote and Depakote ER have a boxed warning for the risk of harm to a fetus if taken during pregnancy. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

If you become pregnant while taking Depakote or Depakote ER, tell your doctor right away. They can advise you on the risks and benefits of continuing treatment with the drug. Your doctor may also recommend a different treatment option for your condition.

If you become pregnant while taking Depakote or Depakote ER, consider enrolling in a pregnancy registry. A pregnancy registry helps gather important information about how a drug can affect pregnancy.

To learn more about the North American Antiepileptic Drug Pregnancy Registry, talk with your doctor. You can also call 888-233-2334 or visit the registry website.

Breastfeeding

It may not be safe to take Depakote or Depakote ER while breastfeeding. The drugs can pass into breast milk. This could cause side effects in a breastfed child.

If you breastfeed while taking Depakote or Depakote ER, it is important to watch the breastfed child for unusual bruising or bleeding. Also watch for signs of jaundice, such as yellowing of the skin or whites of the eyes and pale stools. These could be symptoms of side effects from Depakote and Depakote ER.

If you’re breastfeeding or planning to do so, talk with your doctor. They can discuss the risks and benefits of taking Depakote or Depakote ER while breastfeeding.

Both mild and serious side effects can happen with Depakote and Depakote ER. Most of the drugs’ side effects are mild and should go away with time. However, be sure to tell your doctor if you have bothersome side effects from Depakote or Depakote ER.

If you’d like to learn more about Depakote and Depakote ER, talk with your doctor or pharmacist. They can help answer any questions you have about side effects from taking either drug.

Besides talking with your doctor, you can do some research on your own. These articles might help:

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.