In a number of randomized, controlled clinical trials in the 1990s, Topamax was significantly more effective than a placebo as adjunctive therapy for patients with frequent partial seizures. In reports combining several such studies, about 44% of the patients who took Topamax reduced their seizure frequency by half or more, compared to about 12% of patients who added a placebo. The rate of unwanted side effects was rather high, but many of these patients were given higher doses than are usually given now, with more rapid dose increases.

Topamax has the advantage of providing good control of both primary generalized tonic-clonic seizures and partial-onset seizures. In an add-on study that added Topamax or a placebo to other medications, the rate of primary generalized tonic-clonic seizures was reduced by at least half in 56% of those who took Topamax, versus 20% of those who added a placebo. Other types of generalized seizures were similarly reduced in these patients.

Children with Lennox-Gastaut syndrome have various types of difficult-to-control seizures, including tonic and atonic seizures with stiffening or falling. When Topamax was added to previous medication, the frequency of major seizures was reduced by at least half for 33% of these patients. Only 8% of those who added a placebo had a similar improvement.

Some small studies suggest that Topamax also may be effective when used alone, especially for control of partial seizures.