Levetiracetam for partial seizures

TLDR

The study evaluated the efficacy and safety of adjunctive levetiracetam (500 mg bid and 1500 mg bid) for refractory partial seizures in a double‑blind, randomized, placebo‑controlled multicenter trial. The trial enrolled patients with uncontrolled partial seizures, conducted a 12‑week baseline, then randomized them to placebo or levetiracetam 1000 mg/day or 3000 mg/day with a 4‑week titration, 14‑week fixed dose, and an 8‑week withdrawal or follow‑up period. Levetiracetam significantly reduced partial seizure frequency and increased response rates compared to placebo, with 11 patients becoming seizure free; adverse events were mild to moderate and more common than placebo, yet the drug was well tolerated.

Abstract

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 (<i>p</i> ≤ 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 (<i>p</i> &lt; 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. <b><i>Conclusion:</i></b> Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.