Valproic Acid

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Also known as: Valproate; Free Valproic Acid [Often referred to by brand name (see MedlinePlus Drug Information)]
Formal name: Valproic Acid
Related tests: Carbamazepine; Lamotrigine; Phenytoin; Phenobarbital; Therapeutic Drug Monitoring; Emergency and Overdose Drug Testing

At a Glance

Why Get Tested?

To determine the concentration of valproic acid in the 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 doctor 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 (trough level).

The Test Sample

What is being tested?

This test measures the level of valproic acid in the blood. Valproic acid is a drug that is used primarily to treat certain seizure disorders (also called epilepsy), but is also prescribed to treat bipolar disease and to prevent migraine headaches. It may be prescribed in combination with other antiepileptic drugs such as phenytoin or phenobarbital to control certain kinds of seizures.

Seizure disorders affect the brain's ability to transmit electrical impulses and to regulate nerve activity. During a seizure, a patient may experience changes in consciousness, alterations in sight, smell, and taste, and may experience convulsions. Seizures are associated with acute conditions, such as high fevers, head trauma, severe infections, and exposure to toxins, and with chronic conditions such as metabolic disorders and brain tumors. In many cases, the cause is not known. The frequency of seizures varies from a single episode, to occasional seizures, to recurrent. Rarely, a patient 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. Anti-seizure medications such as valproic acid may be prescribed to lessen the frequency and severity of seizures.

Bipolar disorder is a mental condition that is 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 of the person with bipolar disorder, especially mania. It is also given to some patients with recurrent migraine headaches, not so much to treat migraines as to help prevent their occurrence.

The valproic acid level must be maintained within a narrow therapeutic range. Too little drug and the patient may experience a recurrence of symptoms (seizures, mania, or migraines); too much drug and the patient may experience an increase in the number and severity of side effects. This balance is not always easily achieved. The drug is metabolized by the liver and is processed at a rate that varies from patient to patient and is affected by a patient's age and the health of their liver. In addition, valproic acid can interact with other drugs such as carbamazepine, phenytoin, lamotrigine, and phenobarbital, so monitoring of blood levels may be especially important when someone is taking more than one drug. Furthermore, 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 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.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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

No special test preparation is needed, but patients should talk to their doctor about the timing of the 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 (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 ordered to measure and monitor the amount of valproic acid in the blood to 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 if a patient starts or stops taking additional medications to judge their effect, if any, on the valproic acid level and may be ordered if the patient has a recurrence of symptoms, such as a seizure, a migraine, or bipolar mood swings. Doctors will also evaluate their patient for side effects and adverse reactions during initial dosage adjustments and over time.

Very young and elderly patients are more likely to experience increased side effects. In some cases, the severity of side effects may cause the patient and doctor to seek another anti-seizure, bipolar, or migraine medication.

Sometimes, a doctor may order a free valproic acid test to monitor a person's blood level. Usually, a total valproic acid test is used to monitor the level. In the blood, valproic acid is highly bound to proteins (about 93%) 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. In such cases, measurement of the free valproic acid level is most useful.

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When is it ordered?

A valproic acid level is ordered when a patient begins valproic acid treatment and when/if a patient's 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 patient'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 the patient is complying with therapy (taking the valproic acid regularly). It may also be ordered when a patient 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
  • Rare complications such as liver dysfunction or pancreatitis

A free valproic acid level 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. It may also be ordered if someone is taking other medications.

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What does the test result mean?

The therapeutic range for total valproic acid (bound and unbound) has been established at 50-120 mcg/mL and 6-22 mcg/mL for free valproic acid (unbound only). The range for percent free valproic acid is 5-18%. Within this range, 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 doctor 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 patient is not having recurrent seizures, mood swings, or migraines, and the patient is not experiencing significant side effects, then the dosage is considered adequate. Patients should not increase, decrease, or stop taking their medication without consulting with their doctor as it can increase their risk of having a seizure and may affect other medications that they are taking. Dosage determinations and adjustments must be evaluated on a case-by-case basis.

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Is there anything else I should know?

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 doctors about this subject.

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. Patients should talk to their doctors about all of the drugs and supplements that they are taking and about the medication(s) that are right for them. Valproic acid is not effective for every kind of seizure and will not work for every patient.

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Common Questions

1.  How long will I need to be on valproic acid?

Valproic acid is usually taken every day (sometimes several times a day) for a patient's lifetime. An exception to this may be patients whose seizures are caused by a temporary condition; they may only need the medication for a short period of time.

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2.  How is valproic acid taken?

It may be taken as a tablet, slow release tablet, a liquid, or sprinkled on a soft food. It is generally taken with food to minimize stomach upset, and it is important that the solid forms be swallowed, not chewed, to avoid mouth and throat irritation.

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3.  Can I test my valproic acid level at my doctor's office?

No, it requires specialized equipment. Blood samples are collected from a vein in the arm and tested in the laboratory.

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

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(2007 March 19, Updated). Seizures and Epilepsy: Hope Through Research. NINDS [On-line information]. Available online at http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm through http://www.ninds.nih.gov. Accessed on 3/31/07.

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