As a broad-spectrum antiepileptic drug, valproic acid can be effective against many types of seizures common in children. It has been used for many years to treat children with absence seizures, for which it is just as effective as Zarontin (ethosuximide). These two drugs can be used in combination. Valproic acid also is the first-choice drug for myoclonic seizures in adolescents, including those with juvenile myoclonic epilepsy. It can be effective against generalized tonic-clonic seizures in children, and is a first choice for Lennox-Gastaut syndrome. It is sometimes used to treat infantile spasms (West syndrome). It also controls photosensitivity.

The risk of liver failure is much higher in children under 2 or 3 years of age who take any form of valproate, especially if they are also taking other antiepileptic drugs or if they have a congenital metabolic disorder, a severe seizure disorder with mental retardation, or other brain disease. Consult a pediatric epileptologist before prescribing valproic acid for a child who meets these criteria. The risk of liver failure is much lower in children between 2 and 10 and is very low in older children and adults, perhaps 1 in 50,000. Liver damage usually occurs within the first 6 months of treatment. Diagnosis usually depends on recognition of clinical features, which include vomiting, anorexia, lethargy, and perhaps loss of seizure control, jaundice, or edema. Some doctors recommend carnitine supplements (100 mg/kg/day) for infants and young children who take valproic acid, especially if they have other risk factors for liver damage.

Elevated testosterone levels have been reported in many peripubertal girls taking valproate. Clinical consequences were not evident, but a connection to the later development of polycystic ovary syndrome is possible. Weight gain in these girls may be related to these changes.

Occasionally behavioral changes such as irritability are reported in children who take valproic acid, though it is usually well tolerated.

The initial dose may be 5-10 mg/kg per day, in one to three doses. Steady state is reached after about 2 days of taking a stable dose of valproic acid. The half-life is shorter for children than for adults, so children may require higher doses than adults, commonly 15-60 mg/kg per day. The higher doses are usually needed by children taking combination therapy. Interactions between medications may be so pronounced in children that some never reach the usual therapeutic level of valproate, even with very high doses.

Blood levels fluctuate considerably over the course of a day and are not clearly related to clinical results, so single measurements have limited value for most patients.

The syrup form of valproic acid offers a way of administering valproate to small children who cannot swallow tablets. The time to peak level with the syrup is shorter than for Depakote sprinkle capsules. The overall bioavailability is the same.