Study for Childhood Absence Epilepsy Shows Older Medication to be Most Effective

Cincinnati, March 3, 2010 – The first comprehensive comparative effectiveness clinical trial of three widely used antiseizure drugs for childhood absence epilepsy found the oldest drug is best for treating the disorder, which is the most common form of epilepsy in children.

Published March 4 in the New England Journal of Medicine, data from the comparative clinical trial fill a large information gap in the treatment of childhood absence epilepsy. The research, which identifies important differences between drugs in seizure control and side effects, is expected to impact how physicians select and monitor initial therapy for children with the disorder and ultimately lead to improved outcomes.

“Involving 453 children, 32 U.S. medical centers and the National Institutes of Health, this landmark study establishes clinically important differences between the three medications most commonly used as initial therapy for childhood absence epilepsy,” said Tracy A. Glauser, M.D., the study’s lead investigator and director of the Comprehensive Epilepsy Center at Cincinnati Children’s Hospital Medical Center.

Although childhood absence epilepsy is common, the comparative efficacy and tolerability of initial therapy with ethosuximide, valproic acid or lamotrigine had not been comprehensively or rigorously assessed in patients until the current clinical trial. The study is the largest pediatric epilepsy clinical trial ever funded by the National Institute of Neurological Disorders and Stroke (NINDS), of the National Institutes of Health.

“Although childhood absence epilepsy is often perceived as a benign form of epilepsy, many affected children have cognitive deficits and long-term psychosocial difficulties. This study helps physicians and families make informed choices about how to approach its treatment,” said Deborah Hirtz, M.D., a co-author of the study and a program director at NINDS.

The research team found that ethosuximide provided the best combination of seizure control and fewest attentional side effects over the initial 16- to 20-week period after starting therapy. The researchers concluded that ethosuximide – one of the oldest available anti-seizure medications in the U.S. – is the “sensible choice for initial monotherapy in childhood absence epilepsy.”

Although the clinical trial establishes a rational evidence-based approach for initial drug therapy, the researchers are careful to point out that “even the best empirical therapy fails in almost 50 percent of newly diagnosed cases.” Also, as patients with childhood absence epilepsy grow into adolescence, they are at risk to develop tonic-clonic seizures, which are resistant to treatment by ethosuximide.

“The results of this clinical trial answer important decades old questions and raise new ones” explained Dr. Glauser, also a professor of pediatrics at the University of Cincinnati College of Medicine. “We want to know why specific patients respond differently to different drugs, how we can improve our overall rate of success with initial therapy, and whether those medications that work best in the short-term continue to be the best choice over the long-term.”

Source: Cincinnati Children’s Hospital Medical Center press release. Reviewed by Epilepsy Foundation Professional Advisory Board member Brian Alldredge, PharmD