The United States Food and Drug Administration (FDA) recognizes valproic acid for the treatment of epilepsy and for mania that occurs with bipolar disorder (previously called manic-depressive disorder). Valproic acid is also approved for the prevention of migraine headaches.
Valproic acid's properties in preventing seizures were first discovered in Europe in 1963. The medication was first used clinically in the United Stated in 1978.
Valproic acid is effective in treating a variety of seizure types, which include simple and complex absence seizures, partial seizures, and clonic-tonic seizures (grand mal seizures). Valproic acid is effective in treating the manic episodes of patients with bipolar disorder. Patients who have bipolar disorder resulting from a head injury and patients who do not respond to or who cannot tolerate conventional lithium therapy (normally the therapy of choice for bipolar disorder) can be treated with valproic acid. In addition, valproic acid provides a 50% or greater reduction in the frequency of migraine headaches. Valproic acid is also safe and effective in preventing headaches that arise as a side effect of taking a class of drugs known as selective serotonin reuptake inhibitors (SSRI). These drugs include sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), fluvoxamine (Luvox), and citalopram (Celexa).
Valproic acid comes in 250-mg gelatin capsule and in 250 mg/5ml-syrup.
The dosage of valproic acid used to treat epilepsy depends on the type of seizures the patient has. The doses are determined based on the patient's weight and never based on the patient's age.
The initial dose of valproic acid used to treat mania is 750 mg daily. This dose is then reduced to the lowest dose that will achieve the desired effects. Another dosage strategy is based on patient weight. The starting dose is 30 mg per kilogram of body weight on days one and two followed by 20 mg per kg of body weight taken daily on days three through ten.
For prevention of migraine headaches, a dose of 250 mg twice daily is beneficial. It may take up to 1,000 mg of valproic acid to control migraine attacks.
Patients who have liver disease should not take valproic acid. Pregnant women should not take valproic acid, because it can harm the developing fetus. Patients who are allergic to valproic acid should not take it.
When it is necessary for children under age two and patients who have pancreatitis to take valproic acid, the drug should be used cautiously and with close physician monitoring.
Valproic acid can cause liver damage. Before starting valproic acid therapy, every patient should have a blood test to assess his or her liver function. The risk of valproic acid causing liver damage is greatest during the first six months of treatment. Liver function tests should be done once a month during the first three months, then every three to six months for as long as the patient continues to take the drug. Vomiting, lethargy, anorexia, and jaundice (yellowing of the skin) may precede signs of liver damage. If a patient develops severe or unusual abdominal pain, this may be a sign of pancreatitis (inflammation of the pancreas). Pancreatitis can occur in both children and adults. It can develop shortly after valproic acid is started or after several years of use.
Other side effects of valproic acid may include nausea, vomiting, indigestion, and either diarrhea or constipation. Headaches, dizziness, lack of coordination, confusion, fatigue, tremor, drowsiness, and seizures have also been associated with the use of valproic acid. Behavioral changes associated with the drug including irritability, longer and deeper sleep, hyperactivity, increased sociability, increased sadness, happiness or aggression, are seen more often in children than in adults taking valproic acid.
Fewer than 1% of patients experience appetite changes. These changes may include either diminished or increased appetite. Skin rash, photosensitivity (acute sensitivity to the sun), hair loss, and other hair changes have also been reported in people using valproic acid.
Using valproic acid with other anticonvulsant drugs, such as phenobarbital, clonazepam, and lamotrigine may cause excessive sedation (drowsiness and lack of physical and mental alertness). Valproic acid may diminish the benefits of phenytoin which is another commonly used anticonvulsant.
Taking aspirin during valproic acid therapy may cause valproic acid levels to increase to toxic (poisonous) levels. Other medications that may cause valproic acid toxicity are erythromycin, an antibiotic, and the antidepressant amitriptyline. Drugs that can decrease the effectiveness of valproic acid include carbamazepine and cholestyramine. Ginkgo biloba, an herbal supplement commonly available in the United States, may be prepared with a chemical called 4'-O-methylpyridoxine. If this chemical remains in the herbal preparation, it can cause seizures, and reduce the effectiveness of valproic acid. Severe central nervous depression has been reported with the use of valproic acid and another anticonvulsant called primidone.
Kaplan, Harold. Comprehensive Textbook of Psychiatry. Williams and Wilkins, 1995.
Lacy, Charles F. Drug Information Handbook. Lexi-Comp, Inc. 2002.
Hirschfeld, Robert. "Safety and Tolerability of Oral Loading Divalproex Sodium in Acutely Manic Bipolar Patients." Journal of Clinical Psychiatry. 60 (1999): 815-818.
Ajna Hamidovic, Pharm.D.