Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures

Objective: To evaluate the efficacy and tolerability of levetiracetam ( LEV) as adjunctive therapy in children ( 4 to 16 years) with treatment-resistant partial-onset seizures. Methods: This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day. Results: One hundred ninety-eight patients ( intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant ( 26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group ( 45/101 patients), compared with 19.6% ( 19/97 patients) receiving placebo ( p = 0.0002). Seven ( 6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one ( 1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event. Conclusion: Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.