Valproic acid and the other forms of valproate are highly effective antiepileptic medications. Their effectiveness in controlling seizures has been extensively studied in careful scientific trials in great numbers of patients. (There is little difference in effectiveness between the various types, so we will use the general term "valproate.")

Valproate works against almost every type of epilepsy. It was first approved to treat absence seizures. In a number of studies, valproate has completely controlled absence seizures in a high proportion of patients, and it is widely regarded as the first-choice medication for most patients with absence seizures. (Zarontin [ethosuximide] is the other drug widely used for absence seizures.) Complete control seems more likely when the absence seizures appear alone than when they are combined with another seizure type (Sato et al., 1982).

Most experts also regard valproate as the first choice for treating generalized tonic-clonic seizures. One study (Wilder et al., 1983) compared it with phenytoin in treating a group of patients with newly diagnosed generalized tonic-clonic, clonic, or tonic seizures. Of the patients treated with valproate, 82% had no seizures during the study period after the level of valproate in the blood reached a therapeutic level. The comparable figure for the patients who took phenytoin was 76%.

Photosensitivity is easily controlled by valproate. This medication also seems to be effective in controlling the seizures of juvenile myoclonic epilepsy and myoclonic seizures from other causes, such as benign myoclonic epilepsy of infancy.

Epilepsy syndromes that involve symptomatic generalized seizures, such as infantile spasms and Lennox-Gastaut syndrome, are less well controlled by valproate (or any other medication). Nevertheless, valproate is usually regarded as the first choice for treating these conditions. Some patients do experience substantial improvement and may be able to reduce their use of other seizure medicines that have more troubling side effects.

Researchers looked at whether valproate alone can be used effectively to treat partial seizures. In one large double-blind trial (Mattson et al., 1992), carbamazepine (Tegretol or Carbatrol) was more effective than valproate in controlling complex partial seizures, but valproate was shown to be a valuable alternative. Differences in the side effects need to be considered in choosing medication for each patient.

If valproic acid alone does not fully control the patient's seizures, giving it in combination with another antiepileptic drug may be more effective. Factors influencing the choice of the additional AED may include potential interactions and the mechanisms of action of the two medications. No single combination is perfect for everyone. Sometimes a series of combinations must be tried before finding what is best for the individual patient.

Valproic acid is often used as an "add-on" medication for patients who continue to have complex partial seizures while taking other seizure medicines. In one study, 144 such patients were given either valproic acid or a placebo in addition to the phenytoin (Dilantin) or carbamazepine (Tegretol) that they had been taking. The number of seizures they experienced during the 8 weeks they added either Depakene or a placebo was compared to the number they had during the preceding 8 weeks, when they were taking only Dilantin or Tegretol. The patients taking valproic acid decreased their seizure frequency from16.0 seizures before to 8.9 (7.1 fewer) seizures with add-on therapy. The patients who added a placebo decreased their seizure frequency from 14.5 to 11.5 (3.0 fewer) seizures, a significantly smaller decrease.