Side Effects of Depakote and Depakote ER: What You Need to Know

Depakote and Depakote ER (divalproex) are prescription drugs used to treat epilepsy, migraine, and bipolar disorder. Depakote can cause side effects that range from mild to serious. Examples include weight gain, hair loss, and tremors.

Depakote and Depakote ER* are used to:

• treat focal seizures and absence seizures caused by epilepsy in adults and children ages 10 years or older
• treat mania (episodes of intense high moods, hyperactivity, and similar symptoms) in adults with bipolar disorder
• help prevent migraine headaches in adults

* ER stands for extended release. This means the drug is released into your body gradually over time, starting right after you take a dose. The other forms of Depakote (the tablet and the sprinkle capsule) are delayed release. This means the drug is released into your body a certain amount of time after you take a dose.

The active ingredient in Depakote and Depakote ER is divalproex. (An active ingredient is what makes a drug work.)

Depakote and Depakote ER come as tablets that you swallow. Depakote also comes as a sprinkle capsule. The sprinkle capsule form is prescribed to treat focal seizures and absence seizures in adults and children ages 10 years or older with epilepsy.

Keep reading to learn about the common, mild, and serious side effects (also known as adverse effects) that Depakote and Depakote ER can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may experience mild or serious side effects during Depakote or Depakote ER treatment.

More common side effects in people taking Depakote or Depakote ER include:

• headache
• sleepiness
• weakness
• digestive side effects, such as nausea, vomiting, and diarrhea*
• tremors (uncontrolled shaking)*

These are just a few of the more common side effects reported by people who took Depakote tablets, ER tablets, or sprinkle capsules in studies. These side effects can vary depending on what condition the drugs are being taken to treat.

* To learn more about this side effect, see the “Side effects explained” section below.

Like most medications, treatment with Depakote and Depakote ER may cause mild side effects. Examples of mild side effects that have been reported with Depakote and Depakote ER include:

• belly pain
• dizziness
• headache
• increased or decreased appetite
• insomnia (problems sleeping)
• mild, reversible memory loss
• problems with coordination or walking
• sleepiness
• weakness
• vision problems, such as blurred vision or double vision
• digestive side effects, such as nausea and constipation*
• hair loss*
• tremors (uncontrolled shaking)*
• weight gain or weight loss†

* To learn more about this side effect, see the “Side effects explained” section below.
† To learn more about weight changes with these drugs, see the “Can Depakote and Depakote ER cause weight gain?” section below.

In most cases, these side effects should be temporary. And some may be easily managed, too. But if you have any symptoms that are ongoing or that bother you, talk with your doctor or pharmacist. And don’t stop taking Depakote or Depakote ER unless your doctor recommends it.

Depakote and Depakote ER may cause mild side effects other than the ones listed above. For details, see the prescribing information for the Depakote tablets, Depakote sprinkle capsules, and Depakote ER tablets.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Depakote or Depakote ER, visit MedWatch.

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

• bleeding problems and low blood platelet levels
• high blood ammonia levels
• hypothermia (low body temperature)
• suicidal thoughts and behaviors
• liver damage*†
• pancreatitis (swelling and damage of the pancreas)*†
• fetal harm, if taken during pregnancy*‡
• allergic reaction†

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 if you think you’re having a medical emergency, immediately call 911 or your local emergency number.

* Depakote tablets, Depakote ER tablets, and Depakote 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 effects explained” section below.
‡ To learn more, see “Pregnancy and breastfeeding while taking Depakote or Depakote ER” in the “Warnings for Depakote and Depakote ER” section below.

• Call 911 or your local emergency number.
• Stay with the person until help arrives.
• Remove any guns, knives, medications, or other things that may cause harm.
• Listen, but don’t judge, argue, threaten, or yell.

Get answers to some frequently asked questions about Depakote and Depakote ER’s side effects.

Do older people have a higher risk of Depakote and Depakote ER side effects compared with younger adults?

Yes, older people may have a higher risk of certain side effects of Depakote and Depakote ER. In studies of Depakote tablets, ER tablets, and sprinkle capsules, people ages 65 years or older were more likely to report:

• accidental injury
• infection
• pain
• sleepiness
• tremors (uncontrolled shaking)*

To learn more about your risk of side effects with Depakote or Depakote ER, talk with your doctor or pharmacist. They can tell you more about whether your health history, including your age, puts you at higher risk of side effects.

* To learn more about this side effect, see the “Side effects explained” section below.

Can Depakote and Depakote ER cause long-term side effects?

Yes, it’s possible for Depakote and Depakote ER to cause long-term side effects.

Liver damage, including liver failure, has been reported. Pancreatitis (swelling and damage of the pancreas) has also been reported, including in people who’ve taken Depakote for years. Liver damage and pancreatitis are long-term side effects.

Depakote and Depakote ER have a boxed warning for risk of liver damage and pancreatitis. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). See “Side effects explained” below to learn more.

You can also talk with your doctor or pharmacist to learn more about long-term side effects with Depakote and Depakote ER.

If I take too much Depakote or Depakote ER, will I have overdose symptoms?

Yes, taking too much Depakote or Depakote ER can cause overdose symptoms, such as:

• deep (severe) coma
• heart block (irregular heart rhythm due to a problem with the heart’s electrical signals)
• high blood sodium levels
• sleepiness

In very rare cases, death has occurred due to overdose with Depakote or Depakote ER.

Do not take more Depakote or Depakote ER than your doctor prescribes. If you think you’ve taken too much Depakote or Depakote ER, call your doctor right away. You can also call 800-222-1222 to reach America’s Poison Centers or use its online resource. If you have severe symptoms, immediately call 911 or your local emergency number. Or go to the nearest emergency room.

Can Depakote and Depakote ER cause sexual side effects in men and women?

It’s possible. Studies have found that valproic acid can affect sex hormones and cause certain sexual side effects. The active drug* in Depakote and Depakote ER, divalproex sodium, is a form of valproic acid.

Sexual side effects of valproic acid can include erectile dysfunction in males† and period irregularities in females.† Valproic acid can also decrease libido (sex drive).

If you’re concerned about sexual side effects with Depakote or Depakote ER, talk with your doctor. They may be able to recommend treatment for any sexual problems you’re having. They may also suggest stopping Depakote or Depakote ER and trying a different medication for your condition.

* The active drug is the ingredient that makes a medication work.
† Sex and gender exist on spectrums. Use of the terms “male” and “female” in this article refers to sex assigned at birth.

Does the risk of side effects increase with higher doses of Depakote or Depakote ER (125 mg, 250 mg, 500 mg)?

It’s possible. But in most of the studies of Depakote tablets, ER tablets, and sprinkle capsules, researchers didn’t compare how different doses might have impacted side effects. So it’s not known whether the risk of most side effects increases with higher doses.

It is known that if you take Depakote or Depakote ER while pregnant, the risk of fetal harm increases with higher doses. Depakote and Depakote ER have a boxed warning about risk of fetal harm. For details, see “Pregnancy and breastfeeding while taking Depakote or Depakote ER” in “Warnings for Depakote and Depakote ER” below.

You can also talk with your doctor or pharmacist for more information.

Taking Depakote and Depakote ER can cause weight gain. This side effect was reported in studies of Depakote tablets, ER tablets, and sprinkle capsules.

Weight loss, increased appetite, and decreased appetite were also reported. Appetite changes can affect your weight.

Keep in mind that appetite loss can be a sign of serious side effects from Depakote or Depakote ER. These include liver damage and pancreatitis (swelling and damage of the pancreas). Depakote and Depakote ER have boxed warnings for these side effects.*

If you’re concerned about weight gain while taking Depakote or Depakote ER, talk with your doctor. They can suggest ways to maintain a weight that’s healthy for you.

* Boxed warnings are the most serious warnings from the Food and Drug Administration (FDA). See “Side effects explained” below for more information.

No, withdrawal symptoms haven’t been reported with Depakote tablets, ER tablets, or sprinkle capsules. These are side effects that can happen when you stop taking a medication your body is dependent on.

Depakote and Depakote ER aren’t known to cause dependence or withdrawal. (With dependence, your body needs the drug to feel like it usually does. And withdrawal symptoms are side effects that can occur when you stop taking a drug that your body has become dependent on.)

But stopping Depakote or Depakote ER could cause symptoms of your condition to return. For example, if you’re taking the drug to help prevent migraine headaches, stopping the medication could cause your migraine headaches to return.

Talk with your doctor if you’re interested in stopping Depakote or Depakote ER. They can advise you on how to do it safely. They can also discuss other treatment options for your condition.

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

Hair loss

It’s possible to have hair loss as a side effect from taking Depakote or Depakote ER. This side effect was reported by people taking the medication to treat seizures or help prevent migraine headaches. It wasn’t common, though.

Hair loss wasn’t reported by people taking Depakote or Depakote ER to treat mania caused by bipolar disorder. (Mania refers to episodes of intense high moods, hyperactivity, and similar symptoms.)

Hair lost during treatment will usually grow back after you stop taking Depakote or Depakote ER.

What might help

Contact your doctor if you have hair loss that bothers you while taking Depakote or Depakote ER. They may recommend a treatment for this side effect. Or they may recommend trying a different treatment for your condition.

Tremors

Tremors are a possible side effect of Depakote and Depakote ER. Having tremors means you have shaking that you can’t control, which might affect one body part (such as one hand).

This side effect was most common in people taking the medication to treat seizures. Also, people ages 65 years or older may have a higher risk of tremors than younger adults.

What might help

If you have tremors that bother you while taking Depakote or Depakote ER, talk with your doctor. They can evaluate your symptoms for causes besides Depakote. If they determine that stopping Depakote is best for you, they can also recommend other treatments for your condition.

Digestive side effects, such as nausea and constipation

Digestive side effects are possible with Depakote and Depakote ER. These may include:

Nausea, vomiting, and diarrhea were some of the more common side effects of Depakote and Depakote ER.

What might help

Contact your doctor if you have digestive side effects while taking Depakote or Depakote ER. They can suggest treatment depending on the symptoms you have. If you have symptoms that bother you or don’t go away, your doctor may suggest a different treatment for your condition.

Liver damage

Liver damage is a rare side effect of Depakote or Depakote ER. These drugs have a boxed warning about risk of liver damage.

Boxed warnings are the most serious warnings from the Food and Drug Administration (FDA). They alert doctors and patients about drug effects that may be dangerous.

Liver damage from Depakote or Depakote ER can cause liver failure. This can be life threatening in extreme cases. But liver damage and liver failure weren’t common in studies of Depakote tablets, ER tablets, or sprinkle capsules.

Liver damage is more likely to happen during your first 6 months of taking Depakote or Depakote ER. But this side effect can happen at any time during treatment. And liver damage caused by Depakote can be long term.

Symptoms of liver damage can include:

• appetite loss
• extreme tiredness or fatigue (low energy)
• generally feeling unwell
• jaundice (yellowing of the skin or the whites of your eyes)
• pain in your upper right belly
• swelling in your face
• weakness
• vomiting

Due to the risk of liver damage, doctors usually will not prescribe Depakote or Depakote ER if you have liver problems. They also won’t prescribe Depakote or Depakote ER to people with certain mitochondrial disorders.*

While taking Depakote or Depakote ER, your doctor will closely monitor your liver health using blood tests. Your doctor can tell you more about how often you’ll have these tests while taking Depakote.

* See the “Warnings for Depakote and Depakote ER” section below for details.

What might help

If you notice symptoms of liver damage, contact your doctor right away. They’ll likely want to examine you. If they determine that you might have liver damage, they’ll likely have you stop taking Depakote.

Pancreatitis

Pancreatitis is a rare possible side effect of Depakote or Depakote ER. These drugs have a boxed warning about this side effect.

Pancreatitis refers to inflammation (swelling and damage) in your pancreas. Symptoms of this condition can include:

• nausea or vomiting that doesn’t go away
• severe belly pain, which might spread to your back
• appetite loss

This side effect was very rare in studies of Depakote tablets, ER tablets, and sprinkle capsules. It can be life threatening or fatal in extreme cases.

What might help

Call your doctor right away if you notice symptoms of pancreatitis. Or call your local emergency number or go to the closest emergency room.

If your doctor confirms that you’re experiencing pancreatitis, they’ll have you stop taking Depakote or Depakote ER. They’ll also treat the pancreatitis. This may require treatment in the hospital.

Allergic reaction

Like most drugs, Depakote and Depakote ER can cause an allergic reaction in some people. This side effect wasn’t common in studies of Depakote tablets, ER tablets, or sprinkle capsules.

Symptoms can be mild or serious and can include:

• skin rash
• itchiness
• flushing (temporary warmth, redness, or deepening of skin color)
• swelling under your skin, usually in your eyelids, lips, hands, or feet
• swelling of your mouth, tongue, or throat, which can make it hard to breathe

Rarely, Depakote and Depakote ER can also cause a kind of allergic reaction called drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS is most likely to occur within 2 to 6 weeks of starting treatment. DRESS can be life threatening or fatal in very rare cases.

DRESS often begins as a rash on the face and upper body. Other symptoms can include:

• burning pain in your skin
• swelling in your face
• fever
• itchiness
• swelling in your lymph nodes (such as in your armpits or your neck)
• organ damage

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. They may suggest an over-the-counter antihistamine you take by mouth, such as Benadryl (diphenhydramine). Or they may suggest a product you apply topically (to your skin), such as hydrocortisone cream.

If your doctor confirms you had a mild allergic reaction to Depakote or Depakote ER, they’ll decide if you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you had a serious allergic reaction to Depakote or Depakote ER, they may have you switch to a different treatment.

• what dose you were taking when you had the side effect
• how soon after starting that dose you had the side effect
• what your symptoms were
• how your symptoms affected your daily activities
• what other medications you were also taking
• any other information you feel is important

There are certain warnings to consider before taking Depakote or Depakote ER.

Boxed warnings

Depakote and Depakote ER have several boxed warnings . Boxed warnings are the most serious warnings from the Food and Drug Administration (FDA). Depakote and Depakote ER’s boxed warnings are for risks of:

• Liver damage. Depakote or Depakote ER can cause life threatening liver damage.
• Pancreatitis (swelling and damage of the pancreas). Depakote or Depakote ER can cause pancreatitis, which can be life threatening.
• Fetal harm. Taking Depakote or Depakote ER while pregnant can cause fetal harm.

For details about liver damage and pancreatitis, see the “Side effects explained” section above. And for more about fetal harm, see “Pregnancy and breastfeeding while taking Depakote or Depakote ER” below.

Other warnings

Depakote and Depakote ER may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take Depakote or Depakote ER. The list below includes factors to consider.

Mitochondrial disorder. Having certain mitochondrial disorders can raise your risk of serious side effects, including liver damage, with Depakote or Depakote ER. Mitochondrial disorders are rare conditions caused by genetic changes that affect mitochondria (structures inside cells that produce energy). Due to the risk of liver damage, doctors usually won’t prescribe Depakote if you have certain mitochondrial disorders, such as Alpers-Huttenlocher syndrome. Your doctor can tell you about other treatment options that may be safer for you.

Mood problems, including depression or suicidal thoughts. Like all drugs prescribed to treat epilepsy, taking Depakote and Depakote ER can increase your risk of suicidal thoughts or behaviors. They can also cause or worsen depression. If you have mood problems or have had them before, be sure to tell your doctor. They can help decide whether Depakote or Depakote ER is safe for you to take.

Urea cycle disorder. If you have urea cycle disorder, your doctor usually won’t prescribe Depakote or Depakote ER. Rarely, life threatening or fatal blood levels of ammonia have been reported when people with this condition took Depakote tablets, ER tablets, or sprinkle capsules. Talk with your doctor about other treatments for your condition that may be safer for you to take..

Allergic reaction. If you’ve had an allergic reaction to Depakote or Depakote ER or any of their ingredients, your doctor will likely not prescribe any form of Depakote for you. Ask your doctor what other medications are better options.

Alcohol, Depakote, and Depakote ER

It may be best to avoid or minimize drinking alcohol while taking Depakote and Depakote ER.

Alcohol can worsen some side effects of Depakote and Depakote ER. These include dizziness, sleepiness, and liver damage. It’s important to note that Depakote and Depakote ER have a boxed warning for liver damage.*

If you drink alcohol, talk with your doctor about how much, if any, is safe for you to drink while you’re taking Depakote or Depakote ER.

* A boxed warning is the most serious warning from the FDA. See “Side effects explained” below for more information.

Pregnancy and breastfeeding while taking Depakote or Depakote ER

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

Pregnancy

Depakote and Depakote ER have a boxed warning about fetal harm (commonly known as birth defects) if the drug is taken during pregnancy.

Studies of Depakote tablets, ER tablets, and sprinkle capsules have shown that taking these drugs while pregnant can result in serious problems in a fetus. These problems may include brain and spinal cord problems, and physical abnormalities of the heart, head, arms, or legs. It may also increase the risk of developmental conditions, including autism.

Your doctor will likely recommend that you don’t take Depakote or Depakote ER if you’re pregnant or planning to become pregnant. If you can become pregnant, your doctor will recommend using effective birth control during Depakote or Depakote ER treatment.

If Depakote or Depakote ER are the only medications that work to manage your seizures, your doctor may prescribe the drug even if you’re pregnant or planning pregnancy. In this case, you and your doctor will discuss your treatment plan and the risks and benefits of Depakote treatment.

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

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

Talk with your doctor if you have questions about Depakote or Depakote ER and pregnancy.

Breastfeeding

Depakote and Depakote ER are known to pass into breast milk if taken while breastfeeding. These drugs may cause side effects in a child who’s breastfed. Side effects may include unusual bruising or bleeding, and jaundice (yellowing of the skin or the whites of the eyes).

Talk with your doctor about feeding options for your child if you’re prescribed Depakote or Depakote ER. Together you can discuss risks and benefits of Depakote treatment while breastfeeding. If you are breastfeeding while taking Depakote or Depakote ER, be sure to watch for any side effects in the child.

Like most medications, taking Depakote or Depakote ER can result in side effects. In most cases, side effects are mild. But serious side effects are possible.

If you’re considering treatment with Depakote or Depakote ER, talk with your doctor. Ask questions that help you feel comfortable with your treatment choices. Some examples to help get you started are:

• Can Depakote or Depakote ER cause side effects related to the nervous system, such as hallucinations or tardive dyskinesia?
• Are there treatments I can take for the common side effects of Depakote or Depakote ER?
• How do the side effects of Depakote and Depakote ER compare with other medications that might treat my condition?
• If I have side effects while taking Depakote or Depakote ER, will I need to stop taking it?

To learn more about Depakote and Depakote ER, see these articles:

• Depakote and Depakote ER (divalproex sodium)
• Depakote and Cost: What You Need to Know
• Depakote and Depakote ER Interactions: Alcohol, Medications, and Others
• Dosage Details for Depakote and Depakote ER

To get information on different conditions and tips for improving your health, subscribe to any of Austra Health’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.