Overview

Depakote (Valproic Acid) is a drug used for the treatment of petit mal, grand mal, mixed and akinetic-myoclonic seizures. Valproic acid is a prescription medication that has been proven effective in the treatment of epilepsy, chronic migraine headaches, and manic episodes associated with bipolar disorder, also known as manic depression. The valproic acid level in the blood must be maintained within a narrow therapeutic range. Dosage which is too low or too high can fail to alleviate or even worsen a person’s symptoms.

When is the Test needed?

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.

Reference Range Depakote

Valproic acid is an 8-carbon 2-chain fatty acid that is metabolized by the liver and processed at a variable rate based on the patient’s liver function and age, in addition to patient’s other routine medications with which valproic acid may interact. At therapeutic concentrations, valproic acid mediates prolonged recovery of voltage-activated Na+ channels, thereby inhibiting repetitive firing induced by depolarization of cortical and spinal cord neurons. Its action is similar to that of other common anticonvulsants, such as phenytoin and carbamazepine.

The reference ranges for valproic acid are as follows:

  • The therapeutic range for valproic acid (total) is 50-125 µg/mL. The toxic level is greater than 150 µg/mL.
  • The therapeutic range for valproic acid (free) is 6-22 µg/mL. The toxic level is greater than 50 µg/mL; above this threshold concentration, the binding sites on plasma albumin begin to become saturated.
  • The recommended range for the treatment of epilepsy is 50-100 µg/mL total valproic acid. The recommended range for the treatment of acute mania is 85-125 µg/mL total valproic acid.

Toxic symptoms include excessive drowsiness, unsteadiness or slurred speech. If a person on Depakote experiences these symptoms you should call your neurologist. Depakote often leads to a mild increase in liver enzymes in the blood.

Analysis of Result

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.

Drug Interactions

Depakote may interact with other drugs, including other antiepileptic drugs. Phenobarbital, Dilantin (Phenytoin), Tegretol (Carbamazepine) and Lamictal can decrease the Depakote blood level. The blood levels of other antiepileptic drugs can also be affected by Depakote. When used in combination with Depakote, the levels of Phenobarbital, Felbatol or Lamictal can increase. Inform your neurologist if you are taking any other medications.

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