Valproic Acid

Brief Overview:

Valproic acid (Depakene®), divalproex sodium (Depakote®), and valproate sodium (Depacon®) are all essentially the same drug and generally referred to as "valproic acid" or "valproate". Valproic acid is the liquid form for oral administration, divalproex sodium is a pill available in extended release and sprinkle formulations, and valproate sodium is a solution for intravenous administration. Valproic acid is a broad spectrum anti-seizure drug which can be used for focal seizures (complex partial seizures), generalized seizures (absence, myoclonic, and generalized tonic-clonic), as well as infantile spasms. Although somewhat antiquated scientific data support the use of valproic acid for treatment of infantile spasms, it appears to be much less efficacious than hormonal therapies (prednisolone and ACTH), and vigabatrin. Valproic acid has multiple actions, though its precise mechanism of action with regard to infantile spasms is unknown. A major deterent to the use of valproic acid for treatment of infantile spasms is related to so-called "black box warning" which addressed a specific risk of potentially fatal liver injury in children under the age 2 years. Nevertheless, this risk of fatal liver injury is relatively small (approximately 1 in 30,000 exposures, but much higher among children under the age of 2 years, those receiving multiple anti-seizure drugs, and infants with mitochondrial disorders—perhaps even as high as 1 in 500 exposures for this high-risk subgroup) and overall risk-benefit assessment often favors the use of valproic acid for treatment of infantile spasms despite this risk. There are multiple other possible side effects discussed below. Also of note, valproic acid alters the blood levels of many medications which can complicate the simultaneous administration of multiple medications.  


The goal dose of valproic acid ranges from 30 to 80 mg/kg/day, divided in 1 to 3 daily doses, depending on the formulation. (The liquid preparation is usually administered 3 times daily). A low starting dose is usually preferred with systematic escalation in dosage over several weeks to months. An evaluation of the blood level of valproic acid is generally prudent and a typical goal blood level is approximately 50 to 150 µg/mL.

Side Effects:

Valproic acid is associated with many relatively mild side effects typical of other drugs (e.g. nausea, vomiting, rash, headache, fatigue, etc). In rare cases, valproic acid has been associated with potentially fatal liver injury, pancreatitis, and bone-marrow toxicity (aplastic anemia). Furthermore, it is a known teratogen (cause of birth defects), and is notorious for causing weight gain, hair-loss, and is has been associated with ovarian dysfunction (polycystic ovaries). Still, most patients who take valproic acid do not experience side-effects that lead to discontinuation of the medication. Periodic blood tests to monitor organ function are advised on a frequent basis in the first few months of therapy and less-often thereafter. 


This medication should be administered only under the direct supervision of a physician.

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