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Depakote® (divalproex sodium)-Valproic Acid

Brand and Generic Names

• Brand names:
  • Depakene®– immediate release
    • Syrup: 250 mg/5mL (there is 250 mg in one teaspoonful)
    • Capsules: 250 mg
  • Stavzor®– delayed release
    • Capsules: 125 mg, 250 mg, 500 mg
• Generic name: valproic acid
  • Depakote®/Depakote® ER– both are enteric-coated and slow release; Depakote® ER releases more slowly than Depakote®.
    • Depakote tablets: 125 mg, 250 mg, 500 mg
    • Depakote sprinkle capsules: 125 mg
    • Depakote ER tablets: 250 mg, 500 mg
  Generic name: divalproex sodium
  • Depacon®(Valproate sodium)
    • Intravenous (IV) formulation: 100 mg/mL

Note: For the purpose of this document, the medication will be referred to as valproic acid to avoid confusion.Even though valproic acid is available in different names, strengths and formulations all provide the same active medicine. (See below for what you need to know about the different forms).

What is valproic acid and what does it treat?

Valproic acid is an anticonvulsant medication approved for the treatment of seizures (epilepsy) in adults and children, migraine headaches and acute mania associated with bipolar disorder (also known as manic-depression). 

A manic episode, or mania, is when a person experiences several of the following symptoms at the same time: "high" or irritable mood, very high self esteem, decreased need for sleep, pressure to keep talking, racing thoughts or being easily distracted or frequently involved in activities with a large risk for bad consequences (for example, excessive buying sprees).

A depressive episode, or depression, is when a person experiences several of the following symptoms at the same time: "low" or depressed mood (for example, sad, empty, tearful), decreased interest in most or all activities, changes in appetite (usually decreased), changes in sleep (usually poor sleep), loss of energy, feeling worthless/guilty/ hopeless/ helpless, difficulty concentrating, or thoughts of death (suicidal thinking).

Bipolar disorder is a brain disorder (mental illness) which exposes people to these mood changes over the course of time. Bipolar disorder affects more than two million Americans each year, but patients with this disorder can lead fulfilling lives when they receive proper treatment. Unfortunately, many of those with this illness don’t receive treatment.

Medication is an essential part of successful treatment for bipolar disorder. With the proper dosage, valproic acid can reduce manic symptoms, shorten hospitalizations, help prevent future manic episodes and make it possible for an individual to live productively.

What is the most important information I should know about valproic acid?

Bipolar disorder requires long-term treatment. Do not stop taking the valproic acid, even when you feel better. Only your healthcare provider can determine the length of valproic acid treatment that is right for you. Missing doses of valproic acid may increase your risk for a relapse in your mood symptoms. It may also increase the possibility of seizures.

• Do not stop taking valproic acid or change your dose without first talking to your healthcare provider.
• Valproic acid may make you drowsy.  Do not drive or operate machinery until you know how this medication affects you.
• You should not drink or use illegal drugs while taking valproic acid.
• Valproic acid may be prescribed by itself or along with other medications to manage your mood symptoms.
• There are many different ways for valproic acid to be dosed. Higher starting doses (also known as "loading doses") have been shown to be as effective as slower dose increases and may result in a faster therapeutic response in many individuals.
• The amount of valproic acid in the blood can be measured. In the beginning of treatment, your doctor may check your blood once or twice a week to make sure the appropriate level of medication is in your body and to assess for side effects such as changes in blood counts. Once your symptoms are controlled well, blood samples are drawn less frequently.

There is some evidence to suggest that valproic acid may have advantages for subtypes of bipolar illness-such as rapid cycling and mixed states. Be sure to assess with your doctor the type of bipolar illness so you may better match your interventions to it.

Are there specific concerns about valproic acid and pregnancy?

If you are planning on becoming pregnant, notify your healthcare provider so that he/she can best manage your medications. People living with bipolar disorder who wish to become pregnant face important decisions, about the risks and benefits of the medications as they relate to the illness and to the fetus. This is a complex decision as untreated bipolar disorder has risks to the fetus as well as the mother. There are many dimensions to these choices, so be sure to confer with your doctor and caregivers.

For example, exposure to valproic acid during the first three months of pregnancy is associated with increased risk of spinal cord defects (e.g. spina bifida) in the fetus. Bleeding, liver problems, developmental delays and other birth defects have also been reported. In order to decrease this risk, exposure to valproic acid during the first three months should be avoided if possible. Valproic acid can also cause vitamin K deficiency in the baby, which will increase the risk of bleeding. If valproic acid is used during pregnancy, close monitoring of fetal serum levels is recommended and a vitamin K supplement may be necessary.

Regarding breast-feeding, caution is advised since a small amount of valproic acid does pass into breast milk (less than 5 percent). The American Academy of Pediatrics committee on medications in breast-feeding lists valproic acid as “compatible” with breast-feeding.

What should I discuss with my healthcare provider before taking valproic acid?

• Tell your doctor if you have taken valproic acid before.  If you are allergic to valproic acid, tell your doctor and pharmacist exactly what the medication did to you before even taking one dose; .
• Symptoms that are most bothersome to you about your condition;
• If you have thoughts of suicide;
• Medications you have taken in the past to treat bipolar disorder, whether they were effective or caused any adverse effects;
• All other medications you are currently taking (including over the counter products, herbal and nutritional supplements) and any medication allergies you have;
• Any medication side effects you have experienced in the past or are currently experiencing;
• If you are pregnant, plan to become pregnant, or are breast-feeding;
• If you smoke, drink alcohol, or use illegal drugs; or
• Any other chronic medical conditions that you have (especially seizures, liver problems, pancreatitis or bleeding abnormalities).

How should I take valproic acid?

Valproic acid is available in many different forms (for example, liquid, sprinkle capsules, long-acting tablets). Dosages are adjusted based on response and blood level. The usual effective dose range is between 1000 and 2500 mg daily, although lower or higher doses are needed in some cases.

• Take valproic acid with food to minimize stomach cramping, nausea, and vomiting
• Always take valproic acid at the same time every day
• Use a pillbox or a calendar as a reminder to take your medications. If needed, have a family member or friend check-in with you to help you take your medications.
• If you are currently taking valproic acid multiple times a day and find it difficult to remember to take it regularly, ask your health-care provider if an extended-release formulation is right for you.

What differences should I know about the different forms of valproic acid?

Although all forms of valproic acid deliver the same active medication, there are some differences between each form including 1) ease of swallowing, 2) likelihood of stomach upset and 3) number of times the medicine needs to be taken each day.

• Differences in formulation
  • Liquid: Always take it with food to avoid stomach cramping and diarrhea. Do not mix in soda or any other carbonated drinks because it can upset your stomach. Take it 2 – 4 times daily as per your doctor’s instructions.
  • Tablets: Swallow the tablets whole. Chewing the tablets gives an unpleasant taste and can be irritating to the mouth and throat. Take it 2 – 4 times daily as per your doctor’s instructions.
  • Sprinkle capsules: May be swallowed whole or opened and sprinkled onto food like applesauce or pudding. Sprinkle capsules should not be chewed. Take 2 – 3 times daily as per your doctor’s instructions.
  • Long acting tablets/capsules (Stavzor®, Depakote® and Depakote extended–release): These products are NOT equal to each other. Always check the color of the tablets/capsules to make sure it is what your doctor prescribed. Depakote® tablets and Stavzor® capsules may be taken 1 – 3 times a day. Depakote® extended-release tablets can be taken just once a day.

What happens if I miss a dose?

If you miss a dose of valproic acid, take it as soon as you remember if it is not too close to when your next dose is due - discuss this with your healthcare provider. If it is close to your next dose, wait until then to take the medication and skip the missed dose. Do not double your next dose or take more than what you have been told to take.

What should I avoid while taking valproic acid?

• Avoid drinking alcohol or using illegal drugs while taking valproic acid because the beneficial effects of the medication may be decreased and adverse effects may be increased (e.g. sedation, confusion, liver problems).
• Valproic acid may cause dizziness or drowsiness, especially when first starting the medication.  Make sure you know how it will affect you before you drive, operate machinery or do other activities that may be dangerous if you are not alert.

What happens if I overdose?

• If an overdose occurs, whether intentional or accidental, immediate medical attention is necessary. Call your doctor or emergency medical service (911).  You may also contact the poison control center at 1 (800) 222-1222.
• Symptoms that may occur in an overdose include: dizziness, poor coordination, drowsiness, tremor, confusion, nausea and vomiting.  In severe cases, seizures, coma and death can occur.
• A specific antidote for valproic acid does not exist.

What are the possible side effects of valproic acid?

Like all medications, valproic acid has side effects. Most of these will get better or even go away completely as your body gets used to the medicine. Everyone responds differently so let your doctor, pharmacist and other healthcare professionals know how the medication is affecting you.

Remember the lists of side effects below are only possible problems. Nobody gets them all and very few people get the more serious side effects. This list is to help you know when to contact your doctor or pharmacist. It is not meant to scare you. Talk with your healthcare provider if you experience side effects that are bothersome to you.

More common side effects are:

Nausea, diarrhea, drowsiness and dizziness

Less common side effects are:

Valproic acid may cause an increase in your blood levels of ammonia. If this happens, you may get confused, disoriented, or have difficulty thinking. It may also cause a decrease in the levels of platelets in your blood. If this happens, you may notice that you bruise easier than normal.  Blood tests can be used to check the amount of ammonia and platelets in your blood and ensure safety of this medication.

Rare side effects are:

Liver problems, which are rarely severe, may develop on valproic acid, especially in the first six months of treatment. This is most common in young children taking valproic acid and other anticonvulsants for epilepsy. Pancreatitis and decreased blood counts are also rare but serious side effects. Blood tests to monitor blood counts, as well as liver and pancreas function are an important part of treatment with valproic acid, in order to make sure that you are safe.

A fever or rash may be seen within the first few weeks of treatment.  If you develop a fever, rash or itching soon after starting valproic acid, contact your health care provider immediately.

Stopping valproic acid quickly may lead to having a seizure. Do not stop taking valproic acid without discussing it with your healthcare provider.

Talk with your healthcare provider if you experience side effects that are bothersome to you.

Are there any risks for taking this medication for long periods of time?

• Patients taking valproic acid for a long time may experience weight gain. Speak to your healthcare provider if this side effect is bothersome to you.
• Long-term use of valproic acid may lead to some hair loss. Speak to your healthcare provider if you experience this side effect.
• If you experience right-sided stomach pain, severe nausea/vomiting, facial swelling, yellowing of the skin and pale stools, these may be signs of liver problems. If you experience any of these symptoms, contact your healthcare provider immediately.

What other drugs interact with this medication?

• Medications used to treat epilepsy such as phenytoin (Dilantin®), carbamazepine (Tegretol®/ Carbatrol®/Equetro®), rifampin (Rifadin®), or phenobarbital may decrease the levels of valproic acid in the body.
• 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 valproic acid and increase valproic acid blood levels significantly. If you are taking a baby aspirin 81 mg or Aspirin 325 mg once a day for your heart, this should not interfere with valproic acid.
• Valproic acid may increase the levels of some antidepressants such as amitriptyline (Elavil®) and some anti-seizure medications such as phenytoin (Dilantin®), carbamazepine (Tegretol®/ Carbatrol®/Equetro®) and especially lamotrigine (Lamictal®).
• Combining valproic acid with a medication called topiramate (Topamax®) may also increase ammonia levels in your blood.  If this happens, you may get confused, disoriented, or have difficulty thinking.
• Clonazepam (Klonopin®) combined with valproic acid has rarely produced repeated, or prolonged non–convulsive seizures (absence seizures).

 How long does it take for valproic acid to work?

Several weeks are often required for valproic acid to reach its maximum effectiveness; however, improvement in some symptoms may occur sooner.

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

Lifelong mood stabilizer treatment is generally needed in persons with bipolar illness.  Your doctor can best discuss the duration of treatment you need based on your symptoms and course of illness.

Updated by
Sudha Narayanaswamy, Pharm.D., BCPP, CGP
(November 2010)

 

NAMI wishes to thank the College of Psychiatric and Neurologic Pharmacists for producing this fact sheet.

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