Valproate (Depakote)

Brand names:


  • Capsules (immediate release): 250 mg
  • Syrup: 250 mg/5mL


  • Tablets (delayed release): 125 mg, 250 mg, 500 mg
  • Sprinkle capsules (delayed release): 125 mg

Depakote ER®

  • Tablets (extended release): 250 mg, 500 mg


  • Capsules (delayed release): 125 mg, 250 mg, 500

Generic names: valproate (val PROE ate); also divalproex sodium and valproic acid

Note: For the purpose of this document, the medication will be referred to as valproate. Even though valproate is available in different names, strengths, and formulations, all provide the same active medicine.

Medication class: mood stabilizer, anticonvulsant

All FDA black box warnings are at the end of this fact sheet. Please review before taking this medication.

What is Valproate and what does it treat?

Valproate is a mood stabilizer medication that works in the brain. It is approved for the treatment of bipolar disorder (also known as manic depression),seizures (epilepsy), and migraine headaches. Bipolar disorder involves episodes of depression and/or mania.

Symptoms of depression include:

  • Depressed mood, feeling sad, empty, or tearful
  • Feeling worthless, guilty, hopeless, or helpless
  • Loss of interest or pleasure in normal activities
  • Sleep and eat more or less than usual (for most people it is less)
  • Low energy, trouble concentrating, or thoughts of death (suicidal thinking)
  • Psychomotor agitation ('nervous energy')
  • Psychomotor retardation (feeling like you are moving in slow motion)

Symptoms of mania include:

  • Feeling irritable or 'high"
  • Having increased self esteem
  • Feeling like you don't need to sleep
  • Feeling the need to continue to talk
  • Feeling like your thoughts are too quick (racing thoughts)
  • Feeling distracted
  • Getting involved in activities that are risky or could have bad consequences (e.g. excessive spending)

What is the most important information I should know about Valproate?

Bipolar disorder requires long-term treatment. Do not stop taking valproate, even when you feel better.

Only your healthcare provider can determine the length of valproate treatment that is right for you.

Missing doses of valproate may increase your risk for a relapse in your mood symptoms.

Do not stop taking valproate or change your dose without talking to with your healthcare provider first.

In order for valproate to work properly, it should be taken everyday as ordered by your healthcare provider.

Periodically, your healthcare provider may ask you to provide a blood sample to make sure the appropriate level of medication is in your body and to assess for side effects, such as changes in blood cell counts.

Are there specific concerns about Valproate and pregnancy?

If you are planning on becoming pregnant, notify your healthcare provider to best manage your medications. People living with bipolar disorder who wish to become pregnant face important decisions. This is a complex decision since untreated bipolar disorder has risks for the fetus as well as the mother. It is important to discuss the risks and benefits of treatment with your doctor and caregivers.

Valproate has been associated with an increased risk of spinal cord defects (spina bifida). Bleeding, liver problems, decreased IQ scores, developmental delays, and other birth defects have also been reported. There may be precautions to decrease the risk of these effects. Discontinuing mood stabilizer medications during pregnancy has been associated with a significant increase in symptom relapse.

The American Academy of Pediatrics and the World Health Organization consider valproate compatible with breastfeeding.

What should I discuss with my healthcare provider before taking Valproate?

  • Symptoms of your condition that bother you the most
  • If you have thoughts of suicide or harming yourself
  • Medications you have taken in the past for your condition, whether they were effective or caused any adverse effects
  • If you experience side effects from your medications, discuss them with your provider. Some side effects may pass with time, but others may require changes in the medication.
  • Any other psychiatric or medical problems you have
  • All other medications you are currently taking (including over the counter products, herbal and nutritional supplements) and any medication allergies you have
  • Other non-medication treatment you are receiving, such as talk therapy or substance abuse treatment. Your provider can explain how these different treatments work with the medication.
  • If you are pregnant, plan to become pregnant, or are breast-feeding
  • If you drink alcohol or use illegal drugs

How should I take Valproate?

Valproate is usually is taken 1-3 times daily. It may be taken with or without food.

Typically patients begin at a low dose of medicine and the dose is increased slowly over several weeks.

The dose usually ranges from 1000 mg to 2500 mg. Only your healthcare provider can determine the correct dose for you.

Valproate tablets: Swallow whole. Do not crush, chew or split tablets.

Depakote Sprinkle capsules: Swallow whole or sprinkle onto food, such as applesauce or pudding and eat immediately. Do not chew the sprinkle capsule or contents.

Valproate syrup: Measure with a dosing spoon or oral syringe which you can get from your pharmacy.

Use a calendar, pillbox, alarm clock, or cell phone alert to help you remember to take your medication. You may also ask a family member a friend to remind you or check in with you to be sure you are taking your medication.

What happens if I miss a dose of Valproate?

If you miss a dose of valproate, take it as soon as you remember, unless it is closer to the time of your next dose. Discuss this with your healthcare provider. Do not double your dose or take more than what is prescribed.

What should I avoid while taking Valproate?

Avoid drinking alcohol or using illegal drugs while you are taking valproate. They may decrease the benefits (e.g., worsen your condition) and increase adverse effects (e.g., sedation) of the medication.

What happens if I overdose with Valproate?

If an overdose occurs call your doctor or 911. You may need urgent medical care. You may also contact the poison control center at 1-800-222-1222.

A specific treatment to reverse the effects of valproate does not exist.

What are the possible side effects of Valproate?

Common Side Effects

Nausea, diarrhea, weight gain, feeling drowsy or dizzy

Rare Side Effects

Hair loss, liver problems

Low platelets (platelets help the blood to clot. Bruising easier than normal is a symptom of low platelets

Pancreatitis (inflammation of the pancreas). Symptoms of pancreatitis include severe stomach pain, nausea, vomiting, and not feeling hungry

Increased ammonia levels. If this happens, you may get confused, disoriented, or have difficulty thinking.

Serious Side Effects

Studies have found that individuals who take anticonvulsant medications including valproate have suicidal thoughts or behaviors up to 2 times more often than individuals who take placebo (inactive medication). These thoughts or behaviors occurred in approximately 1 in 550 patients taking the anticonvulsant class of medications.

Are there any risks for taking Valproate for long periods of time?

To date, there are no known problems associated with long term use of valproate. It is a safe and effective medication when used as directed.

What other medications may interact with Valproate?

Avoid taking high doses of aspirin (for example, 325 mg three or more times a day) to treat fever or pain. Aspirin can interfere with valproate and increase valproate blood levels significantly. If you are taking aspirin 81 mg to 325 mg once a day for your heart, this should not interfere with valproate.

Combining valproate with topiramate (Topamax®) may increase ammonia levels in your blood. If this happens, you may get confused, disoriented, or have difficulty thinking.

The following medications may decrease the level and effect of valproate:

  • Anticonvulsant medications such as phenytoin (Dilantin®), carbamazepine (Tegretol®/Carbatrol®/Equetro®), and phenobarbital
  • Rifampin (Rifadin®)

Valproate may increase the level and effects of:

  • Amitriptyline (Elavil®)
  • Anticonvulsant medications such as phenytoin (Dilantin®), carbamazepine (Tegretol®/Carbatrol®/Equetro®), and especially lamotrigine (Lamictal®).

Valproate may decrease the level and effects of:

  • Olanzapine (Zyprexa®)

How long does it take for Valproate to work?

It is very important to tell your doctor how you feel things are going during the first few weeks after you start taking valproate. It will probably take several weeks to see big enough changes in your symptoms to decide if valproate is the right medication for you.

Mood stabilizer treatment is generally needed lifelong for persons with bipolar disorder. Your doctor can best discuss the duration of treatment you need based on your symptoms and illness.

Summary of FDA Black Box Warnings

Liver Damage

Serious and fatal liver damage has been associated with valproate. Children under the age of 2 with severe seizure disorders, congenital disorders, organic brain disease and taking multiple anticonvulsant medications are at increased risk. The risk is highest in the first 6 months of treatment. Liver function should be checked with blood tests before starting the medication and then periodically.

Birth Defects

Birth defects have been found in babies born to mothers who took valproate while pregnant.


Life threatening pancreatitis has been reported in children and adults who take valproate. Signs of pancreatitis include severe abdominal pain, nausea, vomiting and inability to keep food down.

Provided by
the College of Psychiatric and Neurologic Pharmacists
(January 2013)