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Depakote side effects and how to avoid them

Depakote treats a variety of conditions but it can produce side effects such as tremors, weight changes, hair loss, and depression

Depakote side effects | Tremors | Weight changes | Rash | Depression | Hair loss | Sexual side effects | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Depakote is a brand-name prescription medicine for the generic drug divalproex sodium or valproic acid. Depakote is in a class of medications called antiepileptic drugs, or anticonvulsants. It works by calming hyperactivity in the brain. It is approved by the Food and Drug Administration (FDA) to prevent and treat seizures, especially in people with epilepsy. Depakote is generally recommended for adults and children 10 years of age and older. It is also used to treat manic episodes associated with bipolar disorder, and to prevent migraine headaches

Depakote has a black box warning for hepatotoxicity and should not be taken by people with liver problems. It can cause serious pancreas damage, so people with a history of pancreatitis should not take it. Pregnant women should not take Depakote either. Like any other medication, it is important to be aware of Depakote side effects and its interactions. Let’s look at what you need to know before taking Depakote. 

RELATED: What is Depakote? 

Common side effects of Depakote

Like all medications, Depakote may cause minor and temporary side effects. In patients taking Depakote, the most common side effects include:

  • Headache
  • Nausea
  • Tiredness
  • Swelling of the arms and legs
  • Loss of appetite
  • Abdominal pain 
  • Skin rash
  • Weight gain
  • Vomiting 
  • Weakness
  • Hair loss
  • Tremor
  • Diarrhea 
  • Blurred vision
  • Increased appetite 
  • Decreased platelet count 
  • Confusion
  • Lightheadedness 


Tremors are a known side effect of Depakote. According to a study, about 4% of patients taking Depakote report developing a tremor, which may affect the hands, arms, head, or eyelids. In rare cases, the lower body is affected. The tremor may not affect both sides of the body equally. If patients develop a tremor and it is affecting their ability to function or their quality of life, they should discuss dosage options with their healthcare provider. Tests may be done to rule out other causes of a tremor.

Weight changes 

Depakote often causes an increased appetite, which can lead to weight gain. People taking it to treat migraine headaches may have decreased serotonin levels, which can also lead to cravings and overeating. Depakote can also cause drowsiness, which may decrease activity level. If weight gain is a concern, patients are encouraged to eat a balanced diet and engage in regular physical activity. If the weight gain continues, patients can discuss other medication options with their healthcare provider. 


A mild rash is a common side effect of Depakote and is often not of concern. However, patients should seek immediate medical attention if they develop fever, a red or purple skin rash, hives, sores in the mouth, blistering and peeling of the skin, swelling of the lymph nodes, swelling of the face, eyes, lips, tongue, or throat, trouble swallowing or breathing, as these may be signs of a serious allergic reaction.  

Serious side effects of Depakote

Some side effects of Depakote are more serious and may require medical attention. These include:

  • Pancreatitis
  • Severe liver damage 
  • Suicidal thoughts and depression
  • Severe rash
  • Rapid weight gain
  • Elevated ammonia in the blood
  • Hypothermia (low body temperature) 
  • Bleeding problems 


Patients taking anticonvulsants for any reason may develop depression, and people with a history of mental illness are at an increased risk of worsening depression while taking Depakote. Patients should talk to their healthcare provider if they notice an increase in depressed thoughts, suicidal thoughts, new or worsening irritability, new or worsening anxiety, panic attacks, trouble sleeping, dangerous impulses, or other changes in their mood or behaviors. 

Other Depakote side effects

Hair loss

According to one study, Depakote has been reported to cause hair loss in less than 3% of patients taking it. It is primarily reported in women who are between 40 and 49 years old. If patients are concerned about Depakote and hair loss, they should discuss this with their healthcare provider. Lowering the dosage of Depakote may alleviate this symptom.

Sexual side effects

Depakote interferes with the endocrine system and, according to one study, can cause reproductive and sexual dysfunction in both men and women. The most common sexual side effects were erectile dysfunction and decreased libido. If patients experience bothersome sexual side effects, they should discuss this with their healthcare provider. 

How long do Depakote side effects last? 

Most side effects of Depakote are temporary and will go away on their own after the medication is stopped. Since everyone metabolizes medications differently, their bodies will adjust to side effects in their own way. Most common side effects, including nausea and tiredness, will improve after two to four months of taking Depakote. 

Depakote contraindications and warnings 

Liver damage

Depakote should not be taken by people with compromised liver function. It can cause serious liver damage, especially in children younger than two years of age. Children younger than 2 years and patients with hereditary mitochondrial disease are at a considerably increased risk of developing fatal hepatotoxicity. Patients should tell their healthcare provider immediately if they experience stomach pain, dark urine, yellowing of the eyes or skin, decreased appetite, itching, skin rash, vomiting, and/or swelling in their feet, as these are symptoms of liver damage. The risk of getting this serious liver damage is more likely to happen within the first six months of treatment. In some cases, liver damage may continue even after stopping the drug.


Depakote can cause pancreatitis in both children and adults, and should not be taken by people with a history of pancreas disease. Patients should tell their healthcare provider if they experience severe stomach pain, sudden change in body temperature, constipation, or lightheadedness.

Pregnancy and breastfeeding

Depakote has been known to cause serious birth defects, such as spina bifida, and should not be taken by women who are pregnant. According to the manufacturer, these defects occur in 1-2 out of every 100 babies born to mothers who use this medicine during pregnancy. Depakote should not be taken by women who plan on becoming pregnant while taking the medication.

Depakote can be passed through breast milk and should not be taken by women who are breastfeeding.

Other restrictions 

  • Some men have become infertile while taking Depakote.
  • People who have had an allergic reaction to valproate, valproic acid, divalproex sodium, or any of the ingredients in Depakote should not take it. 
  • Patients with certain metabolic diseases such as urea cycle disorders should not take Depakote. 
  • Depakote has the potential to cause blood thinning and should not be taken by people with a history of bleeding problems.


Depakote is generally not considered habit-forming. However, stopping Depakote suddenly can cause serious problems. Patients with epilepsy who suddenly stop a seizure medicine can trigger seizures that will not stop. To avoid withdrawal symptoms, patients should discuss slowly stopping treatment with their healthcare provider. Everyone reacts to medications differently, but possible withdrawal symptoms of Depakote may include seizures, dizziness, tremors, irritability, anxiety, and depression. Patients should seek medical advice if these symptoms worsen. 


Patients should take the dose of Depakote prescribed by their healthcare provider. While everyone responds to medication differently, the maximum recommended dose of Depakote is 60 mg/kg/day. 

It is possible to overdose on Depakote if too much is taken. Symptoms of overdose include sleepiness and irregular heartbeat. A rare symptom of an overdose is a coma. Patients should seek immediate medical attention if they take more than their prescribed dose or experience any of these symptoms. 

Depakote interactions

Like any other medication, there are certain drug interactions that should be avoided. Do not take Depakote with: 

  • Anticoagulants, such as warfarin 
  • Other anticonvulsants, including carbamazepine, ethosuximide, lamotrigine, phenytoin, phenobarbital, and topiramate
  • Antidepressants and anxiolytics, including amitriptyline, bupropion, nortriptyline, and phenelzine
  • Antiemetics, including metoclopramide and over-the-counter medications such as antacids
  • Multiple sclerosis agents, including dalfampridine and amifampridine

How to avoid Depakote side effects

1. Take Depakote as prescribed

Read all drug information before starting Depakote, and follow all directions on your prescription label. Depakote is taken orally and comes as a capsule, extended-release tablets called Depakote ER, a delayed-release tablet, a Depakote sprinkle capsule (capsule that contains small beads of medication that can be sprinkled on food), and a syrup (liquid) to take by mouth. 

Dosage will depend on a number of factors including your age, sensitivity to side effects, other medications you are taking, and the reason you are taking Depakote. Take the amount of medication that your healthcare professional has prescribed. The most common Depakote doses are 125 mg tablets, 250 mg tablets, and 500 mg tablets. Take Depakote with food to help prevent the medication from causing stomach pain. 

Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. 

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. 

Do not stop taking Depakote without talking to your healthcare provider. 

2. Discuss your full medical history with your healthcare provider

Tell your doctor of any medications you are taking, including prescription and over-the-counter drugs, vitamins, and herbal supplements. Discuss any medical conditions you have. Let them know if you are pregnant or breastfeeding or planning on becoming pregnant while taking Depakote. Tell your provider if you have a history of pancreas or liver disease, bleeding problems, or certain metabolic diseases such as urea cycle disorder. It’s also important to discuss a history of depression or mental illness and if you’ve ever experienced suicidal ideation as Depakote may increase these thoughts. While taking Depakote, tell your doctor about any side effects or other symptoms you may develop as he or she may want to adjust the dosage. 

3.  Avoid other medications and substances that could make you drowsy

Depakote may make you drowsy. Do not drive or operate heavy machinery until you know how it will affect you. Some people may also experience impairment in thinking and judgment. Do not drink alcohol while taking Depakote, as this may increase your drowsiness. Do not take sleeping pills, narcotic pain medication, or any other substance that may make you drowsy until you know how Depakote will affect you. Keep Depakote and all medications away from children.