12 Depakote Side Effects You Should Know About

Depakote (divalproex sodium) is a medication that treats seizures in adults and children who are at least 10 years old. Other Depakote uses include treating bipolar disorder and preventing migraines in adults. It’s available as a delayed-release (DR) tablet (Depakote) and an extended-release (ER) tablet (Depakote ER). It’s also available as a DR sprinkle capsule (Depakote Sprinkles), but this formulation is only approved to treat seizures.

Though Depakote products can be very effective, they also have risks. Knowing what to watch out for can help you prevent or manage Depakote side effects.

Depakote side effects at a glance

Depakote has been on the market since the 1980s, so we have a lot of information on potential Depakote side effects. Some are considered common and others are more rare. Side effects may vary between the different formulations.

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Common side effects include:

• Nausea and vomiting

• Stomach pain

• Diarrhea

• Headache

• Weakness

• Tiredness

• Tremor

• Dizziness

• Vision problems

• Hair loss

• Infection

• Weight loss or weight gain

More rare side effects include:

• Liver damage

• Birth defects if used during pregnancy

• Inflammation of the pancreas (pancreatitis)

• Bone loss

• Suicidal thoughts and actions

• Bleeding problems

• High ammonia levels, leading to brain problems

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome

Many common side effects — such as nausea, tremor, and tiredness — are more likely to occur with higher doses. And while most of the research we have is with the DR tablet, there’s some evidence that Depakote ER may be less likely to cause side effects than Depakote DR formulations.

1. Gastrointestinal side effects

Gastrointestinal (GI) side effects are the most common Depakote side effects. These include:

• Nausea and vomiting

• Diarrhea or constipation

• Abdominal pain

• Upset stomach

• Loss of appetite that can lead to weight loss

To help prevent GI side effects, your prescriber will start you at a low dose. They’ll slowly increase it until you reach a dose that’s right for you. If you have nausea and vomiting with Depakote, taking your doses with food can help. If you decide to take Depakote with food, it’s best to do this consistently with each dose. 

If this doesn’t help, talk to your prescriber. Many over-the-counter (OTC) and prescription medications can help with GI side effects like nausea and vomiting, diarrhea, and indigestion. But don’t start any medication, even if it’s OTC, without talking to your prescriber first.

Additionally, GI side effects may be less common with Depakote ER versus Depakote DR forms, although research on this is mixed. Talk to your prescriber about which form is right for you.

In rare cases, GI side effects that don’t go away may be a sign that something else is going on. Liver damage or pancreatitis are rare side effects of Depakote that may also cause GI symptoms. Other medical problems unrelated to Depakote can also cause these symptoms. So if you experience GI side effects that are severe or won’t go away, contact your prescriber to discuss next steps.

2. Headaches

Headaches are another common Depakote side effect. This might seem confusing since the DR and ER tablets are FDA approved to prevent migraines in adults. In studies of Depakote, headaches were most often seen in people taking it for seizures. But having a seizure disorder is linked to a higher risk of headaches. So in some cases, experiencing headaches may be due to seizures versus Depakote.

If you have a headache while taking Depakote, talk to your prescriber. They may recommend an OTC pain reliever, like ibuprofen (Advil, Motrin) or acetaminophen (Tylenol). Drinking enough water, exercising, and getting enough sleep can also help.

3. Drowsiness and dizziness

Depakote can cause drowsiness, dizziness, and a lack of energy. This is one reason it’s best to avoid alcohol or other medications that can make you tired or dizzy while taking Depakote. These include opioids, benzodiazepines, and sleep medications. Even some OTC medications like Benadryl (diphenhydramine) are best avoided.

When you first start Depakote or after a dose increase, avoid activities that require alertness, including driving. Once you see how Depakote affects you, talk to your prescriber about whether it’s safe to resume these activities.

If you’re over 65 years old, you may be more affected by drowsiness and dizziness. This can increase your risk of falls, which can cause injuries. You can prevent falls by clearing your floors of anything you might trip on, using bright lighting in your home, and keeping everyday items within easy reach. Still, pay close attention to how you feel and let your prescriber know if these side effects are affecting your ability to complete your daily tasks.

4. Tremors

Tremors (shaky hands) are another common Depakote side effect. In fact, valproate medications are the most likely seizure medications to cause this side effect. Tremors may be more likely in women and adults over 65. They’re also more likely with higher doses. And they can happen at any point during treatment.

If you have bothersome tremors, talk with your prescriber. They may consider lowering your Depakote dose or switching to another medication entirely. Or they may recommend treating your tremor with a medication like propranolol, which is known to help some people with tremors.

5. Double or blurry vision

Several vision problems can occur with Depakote use. These include:

• Blurry vision

• Double vision (diplopia)

• Repetitive, uncontrolled eye movements (nystagmus)

• Lazy eye (amblyopia)

Along with dizziness and drowsiness, vision changes cause balance problems and increase your risk of accidents. So talk to your prescriber if you’re experiencing changes to your vision.

6. Hair loss

Hair loss (alopecia) can also happen with Depakote. And some studies have shown it’s not dose-related. This means that lower doses are as likely as higher doses to cause alopecia. But the research on this is mixed, as some research shows that higher doses are more likely to cause alopecia. 

If hair loss occurs, it’s expected to grow back after stopping Depakote. Interestingly, it can also make your hair more curly, though this is rare. 

Depakote is one of the most likely seizure medications to cause alopecia. So your prescriber may switch you to another medication if this happens to you.

7. Weight changes

Weight gain and weight loss are possible with Depakote. Weight gain can occur with or without fluid buildup (peripheral edema), another Depakote side effect.

In general, most research on weight gain from valproate products is with another medication called valproic acid. This medication is closely related to Depakote. For example, one small study compared valproic acid to lamotrigine (Lamictal), another common seizure medication. The study found that weight gain was more likely with valproic acid and that it occurred in about the first 2 months of treatment, and continued throughout the 8-month study.

On the other hand, taking Depakote can also lead to weight loss. This may be related to its ability to cause drowsiness and weakness, which can make it harder to eat as you usually would.

If you experience any weight changes while taking Depakote, let your prescriber know. They can check to figure out the cause and give you tips to maintain a healthy weight.

8. Liver failure

Depakote has a few boxed warnings. This is the most serious type of warning the FDA can assign a medication. And while these risks aren’t common, they’re important to know about. They can be severe if they occur.

One of these boxed warnings is for liver failure. It’s most likely to happen within the first 6 months of treatment. Symptoms include tiredness, vomiting, or losing weight. Weakness or facial swelling may also occur.

Many symptoms of liver failure are similar to common Depakote side effects. For example, if you’re experiencing tiredness, it may be hard to tell if this is a typical Depakote side effect or a sign of liver issues. Additionally, other serious conditions can also mimic symptoms of liver failure. For example, facial swelling can also be a sign of DRESS syndrome, another serious Depakote side effect.

People with existing liver disease or certain types of mitochondrial disease shouldn’t use Depakote. The risk of liver failure is higher in these groups of people. 

Your prescriber will monitor your liver function using blood tests before and during Depakote treatment. Make sure to complete any blood work that’s ordered for you. If you’re experiencing facial swelling, severe nausea and vomiting, or extreme weakness, these could be signs of liver damage. Seek medical care by going to the nearest emergency room or calling 911.

9. Birth defects

Taking Depakote during pregnancy can cause birth defects in your unborn fetus. These include neural tube defects, heart problems, and abnormalities in bone formation. Some research also shows that taking valproic acid during pregnancy may lead to reduced cognitive abilities in children later on.

Depakote shouldn’t be used to prevent migraines in women who are currently pregnant (or who are able to become pregnant and don’t use birth control). For seizures or bipolar disorder, Depakote should only be used in pregnant women or those who are able to become pregnant if no other medications are suitable.

Women who could become pregnant should use at least one form of birth control while taking Depakote. If you become pregnant during Depakote treatment, contact your prescriber right away. But don’t stop taking Depakote without talking to them first.

Good to know: To make matters more complicated, Depakote may interact with birth control containing estrogen. Birth control containing estrogen (like several types of birth control pills) may lower Depakote levels, making Depakote less effective. So let your prescriber know what form of birth control you’re taking before starting Depakote. Depending on what you’re using, they may adjust your Depakote dose, or suggest another form of birth control that doesn’t contain estrogen.

10. Pancreatitis

Pancreatitis (inflammation of the pancreas) can occur with Depakote. This side effect can happen at any point during treatment, and with any dose. Symptoms of pancreatitis may look like common GI side effects of Depakote, including abdominal pain, nausea and vomiting, and weight loss. However if your abdominal pain is severe, you have vomiting that doesn’t improve, or you’re experiencing severe weight loss, these are possible symptoms of pancreatitis. This requires emergency care, so call 911 or go to the nearest emergency room.

11. Suicidal thoughts and behavior

An increase in suicidal thoughts or behaviors may occur while taking Depakote. This can happen with any seizure medication.

When you first start Depakote (or if your dose increases), watch for any changes in mood or behavior. If you experience signs of new or worsening depression or anxiety, talk to your prescriber immediately.

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the 988 Suicide and Crisis Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.

12. Bleeding problems

Depakote may cause low platelet levels. Platelets are a type of blood cell that helps your blood clot to prevent bleeding after an injury. Having low platelet levels (thrombocytopenia) can increase your risk of bleeding.

Thrombocytopenia may be more likely in women or people 60 years or older. It’s also more likely with higher Depakote doses. Signs of low platelet levels include unusual bruising or bleeding that lasts longer than normal. This may include:

• Gums bleeding while brushing your teeth

• Blood in your stool

• Nose bleeds

• Unusual bruising

If you see an increase in any of these types of bleeding or bruising and it doesn’t stop, go to the emergency room or call 911 to get immediate care.

Your prescriber may ask you to complete blood tests to check your platelet levels. So make sure to complete any blood work they order for you.

When should you seek medical care for Depakote side effects?

If you experience any bothersome Depakote side effects, contact your prescriber. They can help you determine whether your side effects represent something more serious. But know that in most cases, Depakote side effects are mild and can be managed at home.

If you’re experiencing severe side effects, you may need emergency care. Some serious symptoms include:

• Severe mood changes

• Any type of bleeding that won’t stop

• Severe vomiting

• Severe abdominal pain

• Facial swelling

• Extreme weight loss

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Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

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