Today, at the 58th annual conference in New Orleans, Tracy Glauser, M.D., Director,Comprehensive Epilepsy Center at Cincinatti Children's Hospital presented his most recent findings on the use of levetiracetam (Keppra) as an adjunctive (add-on) treatment for children with partial onset seizures.

This study according to Glauser, “Is the first, double blind trial of levetiracetam conducted in children with partial onset seizures. In fact, this study is one of the few trials of its type and magnitude ever completed involving children with epilepsy."

How Was the Study Designed?

The study was a multicenter, double blind, randomized, placebo controlled parallel group international (U.S. and Cananda) study of adjunctive levetiracetam therapy in children 4-16 years old with partial onset uncontrolled seizures. All participants were on one or two standard antiepileptic drugs. Eligible participants were patients who had at least 8 partial onset seizures during an 8-week baseline period. When asked if the age range between the patients in the study had any effect on the results of the study Glauser said, “In children between 4 and 16 years old, partial onset seizures have similar underlying mechanisms, clinical appearances and response to medication.”

Following the 8-week baseline period (during which the patients' other antiepileptic medication dosages were not altered) patients were randomized to receive either levetiracetam add-on therapy (starting at 20 mg/kg/day) or matching placebo add-on therapy. Subsequently, an 8-week evaluation period followed during which all of the child's antiseizure medication dosages were held constant. At the end of the evaluation phase, patients could elect to continue in an open-label, long-term, follow-up trial or enter a 6-week withdrawal period. The treatment period was defined as the titration (6 weeks) and evaluation (8 weeks) periods combined- a total of 14 weeks.

Results

Glauser et al. found significant reduction in partial onset seizure frequency associated with the use of levetiracetam adjunctive therapy in a pediatric population with partial onset seizures. They also found a spectrum of side effects similar to that seen in adults receiving adjunctive levetiracetam therapy. “The primary way we assessed response to levetiracetam was to compare the seizure reduction experienced by patients receiving levetiracetam add-on therapy to the seizure reduction experienced by those patients receiving placebo add-on therapy," said Glauser. In terms of side effects, Glauser et al. were most interested in side effects that occurred 5% or more frequently in the levetiracetam group compared to the placebo group. All side-effects were reported by the patient;no formal questionnaires were completed. “The most common side effect was somulence where 22.8 % in levetiracetam group reported somulence (sleepiness) versus 11.3 % in the placebo group. The next more common side effect was accidental injury where 16.8 % in levetiracetam reported injuries and 10.3 % in placebo group. Accidental injuries include a wide range such as bumps, bruises, bites, scrapes and represent mild types of injuries,” said Glauser. He speculated that the accidental injuries could be a result of either fewer seizures, therefore kids are more active or they could be due to more sedation. Glauser said, “It really is unclear what the underlying reason is for accidental injuries. There are two explanations of equal plausibility."

Implications of the Study

“I think this study provides additional scientific basis and hope for patients/kids whose seizures aren’t yet controlled through medication,” said Glauser. Although levetiracetam has not been approved for the adjunctive treatment of partial onset seizures in the pediatric population, he hopes this study will help further the approval process.

A copy of this abstract is published in Epilepsia 2004, Volume 45, Supplement 7, p. 187.