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Absence epilepsy (daily frequent but brief staring spells) is the most common form of childhood epilepsy. Ethosuximide, valproic acid, and lamotrigine are common treatments for this condition. Investigators compared these three drugs (provided by the manufacturers) in a multisite, double-blind, randomized trial in 453 children (median age, 7 years) with absence seizures confirmed by electroencephalogram. Drug doses were adjusted every 4 weeks based on clinical seizure activity. The primary outcome was treatment effectiveness, defined as a combination of efficacy and tolerability.
After 16 to 20 weeks of treatment, children who received either ethosuximide or valproic acid were significantly more likely to be seizure free and to tolerate the assigned drug than children who received lamotrigine (53% and 58% vs. 29%). Attention dysfunction was significantly more common with valproic acid than with ethosuximide (49% vs. 33%). Discontinuation because of adverse effects did not differ among the three groups.
Glauser TA et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 2010 Mar 4; 362:790.
Vining EPG. Ethosuximide in childhood absence epilepsy — Older and better. N Engl J Med 2010 Mar 4; 362:843.
Comment
The effectiveness of ethosuximide seems to be superior to that of both valproic acid and lamotrigine for treatment of children with absence epilepsy. The authors selected drug effectiveness — the combination of efficacy and tolerability — as the primary outcome because of the varied adverse effect profiles of antiseizure medications. However, the authors note that children with absence seizures are at increased risk for generalized tonic–clonic seizures as they grow older, and, unfortunately, ethosuximide is not effective for this type of seizure. The authors recommend close follow-up.