A double-blind, placebo-controlled, international study of topiramate in 149 infants aged 1-24 months (mean age 12 months) with refractory partial-onset seizures is reported from Seattle Children's Hospital, WA. Topiramate 5, 15, or 25 mg/kg/d or placebo was given for 20 days, and the percentage reduction in daily seizure rate was recorded on a 48-hour video-EEG. Infants with at least 4 seizures in the 2 weeks before the first day of screening and at least 2 electroclinical seizures in the 48-hour baseline vEEG were eligible. The most frequently used AEDs at baseline were valproic acid (56%), phenobarbital (29%), and carbamazepine (17%). The median percentage reduction from baseline in daily seizure rate was not significantly different (p=0.97) between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Comparisons of lower doses of topiramate and placebo were not significant. Similar results were obtained when the analysis was adjusted for sex, and type or number of AEDs at baseline. Treatment side effects occurred more frequently (>10% difference) with topiramate than with placebo. These included fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection. 
COMMENT. In this AED study employing video EEG, topiramate is ineffective as adjunctive therapy for refractory partial-onset seizures in infants aged 1 month to 2 years. In children older than 2 years, topiramate is effective in controlling refractory seizures of multiple types and is well tolerated in doses ranging from 1 to 24 mg/kg/d. (Ritter FJ et al. Ann Neurol 2003;54(suppl 7):E2. Abstract).
In an editorial , Thio LL and Dodson WE comment that results of AED trials in adults and children cannot be extrapolated to infants with severe epilepsy. Infants with milder epilepsies than those in the Novotny trial may respond. Topiramate may be effective in new-onset epilepsy in infants under 2 years of age. Further Class I AED trials in infants should be encouraged.