Objective: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial.
Methods: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (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 with an 8-week medication withdrawal period or entering a follow-up study.
Results: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p </= 0.001 for both groups). More patients responded (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam than placebo, with rates 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 levetiracetam, 11 became seizure free; no patient became seizure free in the placebo group. Treatment-emergent adverse events (>/=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.