Levetiracetam for partial seizures - Results of a double-blind, randomizedclinical trial

Objective: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bi d levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter t rial. Methods: The authors studied patients with uncontrolled partial seizu res (minimum 12 per 12 weeks), regardless of whether they became secondaril y generalized, for 38 weeks. A 12-week baseline was followed by random assi gnment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/d ay (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded wit h an 8-week medication withdrawal period or entering a follow-up study. Res ults: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) w as lower with levetiracetam compared to placebo (p less than or equal to 0. 001 for both groups). More patients responded (defined as minimum 50% reduc tion in partial seizure frequency) to levetiracetam than placebo, with rate s of 33.0% in the 1000 mg/day and 39.8% in the 3000 mg/day group, compared to 10.8% in the placebo group (p < 0.001). Of 199 patients receiving leveti racetam, 11 became seizure free; no patient became seizure free in the plac ebo group. Treatment-emergent adverse events (greater than or equal to 10%) , mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. Conclusion: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.