Comparative Monotherapy Trials and the Clinical Treatment of Epilepsy

Brodie MJ, Perucca E, Ryvlin P, Ben‐Menachem E, Meencke HJ; Levetiracetam Monotherapy Study Group. Neurology 2007;68(6):402–408. OBJECTIVE: We report the results of a prospective study of the efficacy and tolerability of levetiracetam, a new antiepileptic drug with a unique mechanism of action, in comparison with controlled‐release carbamazepine as first treatment in newly diagnosed epilepsy. METHODS: Adults with 2 partial or generalized tonic–clonic seizures in the previous year were randomly assigned to levetiracetam (500 mg twice daily, n = 288) or controlled‐release carbamazepine (200 mg twice daily, n = 291) in a multicenter, double‐blind, noninferiority, parallel‐group trial. If a seizure occurred within 26 weeks of stabilization, dosage was increased incrementally to a maximum of levetiracetam 1,500 mg twice daily or carbamazepine 600 mg twice daily. Patients achieving the primary endpoint (6‐month seizure freedom) continued on treatment for a further 6‐month maintenance period. RESULTS: At per‐protocol analysis, 73.0% (56.6%) of patients randomized to levetiracetam and 72.8% (58.5%) receiving controlled‐release carbamazepine were seizure free at the last evaluated dose (adjusted absolute difference 0.2%, 95% CI – 7.8% to 8.2%) for 6 months (1 year). Of all patients achieving 6‐month (1‐year) remission, 80.1% (86.0%) in the levetiracetam group and 85.4% (89.3%) in the carbamazepine group did so at the lowest dose level. Withdrawal rates for adverse events were 14.4% with levetiracetam and 19.2% with carbamazepine. CONCLUSIONS: Levetiracetam and controlled‐release carbamazepine produced equivalent seizure freedom rates in newly diagnosed epilepsy at optimal dosing in a setting mimicking clinical practice. This trial has confirmed in a randomized, double‐blind setting previously uncontrolled observations that most people with epilepsy will respond to their first‐ever antiepileptic drug at low dosage.