Levetiracetam use in children

Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures.

BACKGROUND: Currently, there are no published randomized controlled trials evaluating the efficacy and safety of adjunctive antiepileptic therapy in idiopathic generalized epilepsy with myoclonic seizures.

METHODS: This randomized, double-blind, placebo-controlled multicenter trial assessed the efficacy and tolerability of adjunctive treatment with levetiracetam 3,000 mg/day in adolescents (>or=12 years) and adults (<or=65 years) with idiopathic generalized epilepsy, who experienced myoclonic seizures on >or=8 days during a prospective 8-week baseline period, despite antiepileptic monotherapy. The 8-week baseline period was followed by 4-week up-titration, 12-week evaluation, and 6-week down-titration/conversion periods.

RESULTS: Of 122 patients randomized, 120 (levetiracetam, n = 60; placebo, n = 60) were evaluable. Diagnoses were either juvenile myoclonic epilepsy (93.4%) or juvenile absence epilepsy (6.6%). A reduction of >or=50% in the number of days/week with myoclonic seizures was seen in 58.3% of patients in the levetiracetam group and in 23.3% of patients in the placebo group (p < 0.001) during the treatment period. Levetiracetam-treated patients were more likely to respond to treatment than patients receiving placebo (OR = 4.77; 95% CI, 2.12 to 10.77; p < 0.001). Levetiracetam-treated patients had higher freedom from myoclonic seizures (25.0% vs 5.0%; p = 0.004) and all seizure types (21.7% vs 1.7%; p < 0.001) during the evaluation period. The only adverse events more frequent with levetiracetam were somnolence and neck pain.

CONCLUSION: These results suggest that levetiracetam is an effective and well-tolerated adjunctive treatment for patients with previously uncontrolled idiopathic generalized epilepsy with myoclonic seizures. (Noachtar S, Andermann E, et al.Neurology. 2008 Feb 19;70(8):607-16.)

An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy.

OBJECTIVE: To conduct an open-label, add-on trial on safety and efficacy of levetiracetam in severe myoclonic epilepsy of infancy (SMEI). Patients and METHODS: SMEI patients were recruited from different centers according to the following criteria: age > or =3 years; at least four tonic-clonic seizures/month during the last 8 weeks; previous use of at least two drugs. Levetiracetam was orally administrated at starting dose of approximately 10 mg/kg/day up to 50 to 60 mg/kg/day in two doses. Treatment period included a 5- to 6-week up-titration phase and a 12-week evaluation phase. Efficacy variables were responder rate by seizure type and reduction of the mean number per week of each seizure type. Analysis was performed using Fisher exact and Wilcoxon tests. RESULTS: Twenty-eight patients (mean age: 9.4 +/- 5.6 years) entered the study. Sixteen (57.1%) showed SCN1A mutations. Mean number of concomitant drugs was 2.5. Mean levetiracetam dose achieved was 2,016 mg/day. Twenty-three (82.1%) completed the trial. Responders were 64.2% for tonic-clonic, 60% for myoclonic, 60% for focal, and 44.4% for absence seizures. Number per week of tonic-clonic (median: 3 vs 1; p = 0.0001), myoclonic (median: 21 vs 3; p = 0.002), and focal seizures (median: 7.5 vs 3; p = 0.031) was significantly decreased compared to baseline. Levetiracetam effect was not related to age at onset and duration of epilepsy, genetic status, and concomitant therapy. Levetiracetam was well tolerated by subjects who completed the study. To date, follow-up ranges 6 to 36 months (mean, 16.2 +/- 13.4). CONCLUSION: Levetiracetam add-on is effective and well tolerated in severe myoclonic epilepsy of infancy. Placebo-controlled studies should confirm these findings. (Striano P, Coppola A, Pezzella M, et al. Neurology. 2007 Jul 17;69(3):250-4)

Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy.

OBJECTIVE: To assess the efficacy and tolerability of adjunctive levetiracetam in patients with uncontrolled generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsies (IGE). METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults and children (4 to 65 years) with IGE experiencing >or=3 GTC seizures during the 8-week baseline period (4-week retrospective and 4-week prospective), despite receiving stable doses of one or two antiepileptic drugs (AEDs). Patients were randomized to levetiracetam (target dose 3,000 mg/day for adults; 60 mg/kg/day for children) or placebo and a 4-week titration period was followed by a 20-week evaluation period. RESULTS: Of 229 patients screened, 164 were randomized (levetiracetam, n = 80; placebo, n = 84). Levetiracetam produced a greater mean reduction in GTC seizure frequency per week over the treatment period (56.5%) than placebo (28.2%; p = 0.004). The percentage of patients who had >or=50% reduction of GTC seizure frequency per week (responders) during the treatment period was 72.2% for levetiracetam and 45.2% for placebo (p < 0.001; OR 3.28; 95% CI 1.68 to 6.38). During the first 2-week treatment 64.6% of patients on levetiracetam and 45.2% on placebo (p = 0.018) were classified as responders. During the evaluation period the percent of patients free of GTC seizures (34.2% vs 10.7%; p < 0.001) and all seizure types (24.1% vs 8.3%; p = 0.009) was greater for levetiracetam than placebo. Levetiracetam was well tolerated with 1.3% of patients discontinuing therapy due to adverse events vs 4.8% on placebo. CONCLUSION: Adjunctive levetiracetam is an effective and well-tolerated antiepileptic drug for treating generalized tonic-clonic seizures in patients with idiopathic generalized epilepsies.(Berkovic SF, Knowlton RC, et al. Neurology. 2007 Oct 30;69(18):1751-60.)