Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures.

OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures. METHODS: This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day. RESULTS: One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event. CONCLUSION: Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.

Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group.

PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as add-on therapy on health-related quality of life in the treatment of refractory partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if they had >/=12 partial-onset seizures with or without secondary generalization during the 12-week baseline period with a minimum of two seizures every 4 weeks. Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample size based on seizure frequency reduction. The 31-item Quality of Life in Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant differences were found among the three treatment groups for Seizure Worry (p = 0. 0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p = 0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset seizure reduction) had significant improvements in all areas, except Medication Effect, compared with nonresponders (all p > 0.006). Clinically noticeable improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3, 000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas. CONCLUSIONS: Addition of LEV to standard medication seems to have a positive impact on health-related quality of life, particularly among responders in this short-term study. These exploratory analyses require additional studies to evaluate long-term changes in a larger population.

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (p /=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.