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Valproic Acid


At a Glance

Why Get Tested?

To determine the concentration of valproic acid in your blood and to maintain a therapeutic level

When to Get Tested?

At regular intervals to monitor the drug's level; to detect low or excessive (potentially toxic) concentrations

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

No special test preparation needed, but talk to your health care provider about the timing of sample collection. Since dosage timing varies and some formulations are time-released, collection specifics may vary. Often, the recommended time for sample collection is just before the next dose is taken.

The Test Sample

What is being tested?

Valproic acid is a drug that is used primarily to control certain seizures by lessening their severity and frequency. It may be prescribed in combination with other antiepileptic drugs such as phenytoin or phenobarbital. The valproic acid level in the blood must be maintained within a narrow therapeutic range. This test measures the level of valproic acid in the blood.

Seizure disorders affect the brain's ability to transmit electrical impulses and to regulate nerve activity. During a seizure, someone may experience changes in consciousness, alterations in sight, smell, and taste, and may experience convulsions. Seizures are associated with several conditions but, in many cases, the cause is not known. The frequency of seizures varies from a single episode, to frequent, recurrent seizures. Rarely, someone may have a seizure that does not stop without prompt medical intervention. People may experience some fatigue and a short period of confusion after a seizure. Muscle contractions during a seizure can lead to an injury and, in some cases, recurrent seizures can eventually lead to progressive brain damage but, for most people, there will be little or no residual damage.

Sometimes valproic acid is prescribed for bipolar disorder, a psychiatric condition characterized by cycles of depression and mania that may last for days, weeks, months, or years. During a depressive episode, those affected may feel sad, hopeless, worthless, and have thoughts of suicide. During a manic episode, those affected may be euphoric, irritable, use poor judgment, and participate in risky behaviors. Valproic acid is prescribed to help even out the moods, especially those of mania, of the person with bipolar disorder. The drug is also used to treat people with recurrent migraine headaches to help prevent their occurrence and to treat certain chronic pain syndromes.

The valproic acid level in the blood must be maintained within a narrow therapeutic range. If the level is too low, someone may experience a recurrence of symptoms, but, if the level is too high, someone may experience an increase in the number and severity of symptoms and side effects. The balance is often difficult to achieve because the drug is metabolized by the liver and is processed at a rate that varies from person to person and is affected by age and liver health.

Most valproic acid is bound to protein in the blood and it is the unbound "free" portion that is active. If someone has a condition that results in a lower than normal amount of protein in their blood, then that person may have an excess of active "free" valproic acid.

Dosages of valproic acid must be adjusted carefully until a steady concentration in the blood is reached.The actual amount of drug that it takes to reach this steady state will vary from person to person and may change over time.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?

No special test preparation is needed, but patients should talk to their health care provider about the timing of the sample collection. Since dosage timing varies and some formulations are time-released, collection specifics may vary. Often, sample collection is recommended for when levels are at their lowest (trough level). This ensures that the minimum amount of drug to be effective is maintained in the blood.

The Test

How is it used?

The valproic acid test is used to measure and monitor the amount of valproic acid in the blood and determine whether the drug concentration is within the therapeutic range.

The prescribed dose of the drug may be adjusted up or down depending on the results of the blood test. The test may then be ordered at regular intervals, and as needed, to ensure that therapeutic blood concentrations are maintained.

One or more valproic acid tests may be ordered when someone starts or stops taking additional medications to judge their effect, if any, on the valproic acid level and may be ordered if the person has a recurrence of symptoms, such as a seizure, a migraine, or bipolar mood swings. Health practitioners will also evaluate their patients for side effects and adverse reactions during initial dosage adjustments and over time.

While total valproic acid tests are usual, health practitioners may order a free valproic acid test to monitor blood levels of the drug in patients with certain conditions or in particular disease states. Valproic acid in the blood is highly bound to proteins and only the portion of valproic acid that is unbound or "free" is pharmacologically active. Under normal conditions, the balance between bound and unbound valproic acid in the blood is relatively stable, so measuring the total valproic acid is appropriate for monitoring the therapeutic level. However, in certain conditions and disease states, that balance can be disturbed, the percentage of free or active valproic acid can increase, and the person may experience symptoms of toxicity even though their total valproic acid result falls within the therapeutic range.

When is it ordered?

A valproic acid test is ordered when someone begins valproic acid treatment as well as if and when their medications change (other drugs are started, stopped, or changed). Once a stable blood concentration in the therapeutic range has been achieved, the valproic acid level may then be monitored at regular intervals to ensure that it remains within this range.

The test may be ordered when a person's condition does not appear to be responding to valproic acid to determine whether the concentration is too low, the medication is ineffective, and/or to determine if someone is complying with therapy (taking the valproic acid regularly). It may also be ordered when someone experiences a troublesome level of side effects and/or develops complications. These side effects may include some or a combination of the following:

  • Gastrointestinal symptoms such as nausea, vomiting, diarrhea
  • Dizziness
  • Unusual weight gain or loss
  • Tremors
  • Blurred or double vision, uncontrolled eye movements
  • Mood swings
  • Unusual bruising and bleeding
  • Hives
  • Hair loss
  • Ringing in the ears
  • Back pain

The very young and the elderly are more likely to experience increased side effects.

Rare but serious side effects requiring medical attention include unusual bruising or bleeding, tiny purple or red spots on the skin, fever, blisters or rash, bruising, hives, difficulty breathing or swallowing, confusion, fatigue, vomiting, drop in body temperature, and weakness in the joints.

A free valproic acid test may be ordered when someone has an underlying condition that affects the balance of protein-bound drug, such as low protein level in the blood (hypoalbuminemia) or kidney or liver failure. These conditions increase the risk of having excessive amounts of valproic acid in the blood. Use of certain medications may also prompt a health practitioner to order a free valproic acid test.

What does the test result mean?

The therapeutic range for total valproic acid (bound and unbound) has been established at 50-125 µg/mL and 6-22 µg/mL for free valproic acid (unbound only). The recommended range for the treatment of epilepsy is 50-100 µg/mL total valproic acid, while the recommended range for the treatment of acute mania is 85-125 µg/mL total valproic acid.

Within these ranges, most people will respond to the drug without excessive side effects; however, response varies with each individual. Some people will experience seizures, mood swings, or migraines at the low end of the therapeutic range while some people will experience excessive side effects at the upper end. Patients should work closely with their health practitioner to find the dosage and concentration that works the best for them.

In general, if the valproic acid result is within the therapeutic range, the person is not having recurrent seizures, mood swings, or migraines, and is not experiencing significant side effects, then the dosage is considered adequate.

People should not increase, decrease, or stop taking their medication without consulting with their health care provider as it can increase the risk of having a seizure and may affect other medications being taken. Dosage determinations and adjustments must be evaluated on a case-by-case basis.

Is there anything else I should know?

Rare complications associated with use of valporic acid include pancreatitis and liver dysfunction. Serious liver damage is most likely to occur within the first six months of therapy.

While severe liver injury is rare, mild increases in liver-related enzymes (AST and ALT) occur in up to 20% of those taking valproic acid; these usually return to normal even if the drug is continued.

The use of valproic acid during pregnancy is associated with an increased risk of several birth defects, especially neural tube defects such as spina bifida. Women of child-bearing age should talk to their health practitioner about this.

A variety of prescribed drugs, over-the-counter medications, and supplements can increase, decrease, or interfere with the concentrations of valproic acid in the blood. Tell your health care providers about all prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking.



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