Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures

Area of Science:

• Pediatric Neurology
• Clinical Pharmacology
• Epileptology

Background:

• Refractory partial-onset seizures (POS) in infants present a significant clinical challenge.
• Limited effective treatment options exist for infants with drug-resistant epilepsy.
• Topiramate is an established antiepileptic drug, but its efficacy in young children with refractory POS is not well-defined.

Purpose of the Study:

• To assess the efficacy and safety of adjunctive topiramate in infants with refractory partial-onset seizures (POS).
• To determine if different dosages of topiramate (5, 15, or 25 mg/kg/d) improve seizure control compared to placebo.
• To identify any new safety concerns associated with topiramate use in this population.

Main Methods:

• A double-blind, placebo-controlled, international study involving 149 infants (aged 1-24 months) with refractory POS.
• Participants were randomized to receive adjunctive topiramate (5, 15, or 25 mg/kg/d) or placebo for 20 days.
• The primary outcome measure was the median percentage reduction in daily POS rate, assessed via 48-hour video-EEG.

Main Results:

• No significant difference in the median percentage reduction of daily POS rate was observed between the topiramate 25 mg/kg group (20.4%) and the placebo group (13.1%).
• Lower doses of topiramate also showed no significant reduction in seizure rates compared to placebo.
• Adverse events such as fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infections were more frequent with topiramate.

Conclusions:

• Adjunctive topiramate at doses of 5, 15, or 25 mg/kg/d was not effective in treating refractory partial-onset seizures in infants aged 1-24 months.
• The study did not reveal any new safety concerns regarding topiramate use in this age group.
• Current evidence suggests topiramate is not a beneficial adjunctive therapy for refractory POS in infants.