Ethosuximide is preferred for childhood epilepsy

The first comprehensive comparative effectiveness clinical trial of three widely used anti-seizure drugs for childhood absence epilepsy ? the most common form of epilepsy in kids ? has established an evidence-based approach for initial drug therapy.

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.

The new study is published in the New England Journal of Medicine. The double-blind, randomized, comparative clinical trial would fill a large information gap in the treatment of childhood absence epilepsy, also known as petit mal epilepsy.

“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 ethosuximide ? one of the oldest available anti-seizure medications in the U.S. ? is the “sensible choice for initial monotherapy in childhood absence epilepsy.”

Of the three drugs, ethosuximide’s freedom-from-failure rate was 53 percent compared to 58 percent for valproic acid and 29 percent for lamotrigine. The freedom-from-failure rates of ethosuximide and valproic acid were similar to each other and both were significantly higher than that for lamotrigine. A significantly lower percentage of children taking ethosuximide (33 percent) had abnormal Conners’ confidence index scores compared to those taking valproic acid (49 percent).

Researchers concluded that ethosuximide was preferred as initial therapy because of its improved seizure control compared to lamotrigine and fewer attentional effects compared to valproic acid.

According to the Epilepsy Foundation, 45,000 children in the United States under the age of 15 develop epilepsy every year. An estimated 10 to17 percent of those cases involve childhood absence epilepsy, an epilepsy syndrome in which seizures can occur dozens to hundreds of times per day. The seizures consist of sudden loss of awareness as children stop activities and stare blankly into space for 10-30 seconds. Children suffering these seizures can be unresponsive to voice and often display flickering eyelids, lip smacking or other non-voluntary movements.

Source: Cincinnati Children’s Hospital Medical Center, USA

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