Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group.
OBJECTIVE
To evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in selected patients with refractory partial seizures.


METHODS
In this multicenter, double-blind, placebo-controlled, parallel-group, responder-selected study, patients were randomized (2:1 ratio) to receive oral LEV 1500 mg twice daily or placebo during a 12-week add-on phase. Treatment responders (patients with a reduction in partial seizure frequency of 50% or more compared with baseline) entered a monotherapy phase that included a maximum 12-week down-titration period and 12 weeks of monotherapy at 1500 mg twice daily. In both phases, responder rate, seizure frequency, and adverse events were analyzed.


RESULTS
A total of 286 patients (placebo, n = 105; LEV, n = 181) entered the add-on phase, and 86 patients (placebo, n = 17; LEV, n = 69) were eligible for the monotherapy phase. Thirty-six of 181 patients (19.9%) who received LEV completed the entire study compared with only 10 of 105 patients (9.5%) in the placebo group (p = 0.029). The odds of completing the study on LEV were 2.36 times (95% confidence interval, 1.08, 5.57) higher than on placebo. The responder rate during the add-on phase was significantly higher in the LEV group compared with the placebo group (42.1% vs. 16.7%, respectively; p < 0.001). In the LEV monotherapy group, the median percent reduction in partial seizure frequency compared with baseline was 73.8% (p = 0.037), with a responder rate of 59.2%. Nine patients (18.4%) remained seizure-free on LEV monotherapy.


CONCLUSIONS
Conversion to LEV monotherapy (1500 mg twice daily) is effective and well tolerated in patients with refractory partial seizures who responded to 3000 mg/d LEV as add-on therapy.
Ben-Menachem
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Department of Clinical Neuroscience, Sahlgrenska, University Hospital, Göteborg, Sweden. ebm@neuro.gu.se
Falter
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D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D000077287:Levetiracetam; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D010919:Placebos; D016896:Treatment Outcome
D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam