Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy

Purpose: To evaluate the long-term clinical usefulness of levetiracetam (LEV, Keppra(R)(1)) as add-on therapy in patients with refractory epilepsy. Methods: Data for all 1422 patients with refractory epilepsy treated with LEV during the development program were analyzed for changes in seizure frequency per week, seizure freedom, and adverse events. Results: Median percent reduction from baseline in seizure frequency per week over the whole treatment period was 39.6%, and no decrease over time was observed within each cohort exposed to LEV for durations ranging from 6 to 54 months. The median treatment period was 399 days (range 1-8 years). The proportion of responders during the first 3 months of LEV treatment was 39.2%. This proportion remained stable at 6 months (36.1%). Overall, 38.6 and 20.1% of patients had reductions in seizure frequency of at least 50 and 75%. Sixty-five (4.6%) patients were seizure-free over their entire treatment period, compared with 167 (11.7%) and 126 (8.9%) during their last 6 and 12 months of follow-up. Ninety-seven (19.8%) of 491 patients who received only one other antiepileptic drug (AED) in addition to LEV were seizure-free during their last 6 months. The proportion of patients who reduced their number of concomitant AEDs was 14.4% (205 patients), while 5.5% (79 patients) were treated with LEV only at the end of follow-tip. Accidental injury (28.0%), infection (26.6%), headache (25.8%), somnolence (23%), asthenia (22.6%), and dizziness (18.9%) were among the most common adverse events. Conclusion: LEV offers sustained efficacy in patients with refractory. partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials. (C) 2002 Elsevier Science B.V. All rights reserved.