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Am Fam Physician. 2011;83(1):81-82

Background: Childhood absence epilepsy is the most common form of epilepsy in children. Ethosuximide (Zarontin), lamotrigine (Lamictal), and valproic acid (Depakote) are options for initial monotherapy, but their relative effectiveness and tolerabilities have not been determined. Glauser and colleagues conducted a double-blind, randomized controlled trial to assess for these effects and determine the optimal therapy for childhood absence epilepsy.

The Study: The authors enrolled 453 children 2.5 to 13 years of age who were newly diagnosed with childhood absence epilepsy. Patients received ethosuximide (maximal dosage: 60 mg per kg or 2,000 mg per day), lamotrigine (maximal dosage: 12 mg per kg or 600 mg per day), or valproic acid (maximal dosage: 60 mg per kg or 3,000 mg per day). Medications could be titrated upward for persistent seizures, up to the maximal allowed dosages. The primary outcome was freedom from treatment failure after 16 to 20 weeks; treatment failure was defined as persistent absence seizures, generalized tonicclonic seizures, or drug-related systemic toxicity. Attentional dysfunction was the secondary outcome, measured by neuropsychological testing at baseline and at the conclusion of the study.

Patients were excluded if they had a history of other types of seizures, severe rashes with any medication, a major psychiatric disease, an autism spectrum disorder, abnormal liver enzymes or complete blood count, or any other clinically significant medical conditions.

Results: Baseline characteristics were similar among the groups, with a median age of seven years, five months. Overall, 47 percent of the patients were free from treatment failure at the end of the study. Patients taking ethosuximide or valproic acid were less likely to experience treatment failure (47 and 42 percent, respectively) compared with those taking lamotrigine (71 percent). More patients were seizure-free with ethosuximide and valproic acid than with lamotrigine (see accompanying table). However, valproic acid was associated with more attentional dysfunction than ethosuximide or lamotrigine.

AgentOdds ratio of controlling seizures without drug toxicityOdds ratio of having persistent seizuresOdds ratio of attentional dysfunction
Ethosuximide (Zarontin; versus lamotrigine [Lamictal])2.660.191.56 (NS)
Valproic acid (Depakote; versus lamotrigine)3.340.163.04
Valproic acid (versus ethosuximide)1.26 (NS)0.84 (NS)1.95

Conclusion: The authors conclude that ethosuximide and valproic acid are more effective than lamotrigine in controlling seizures associated with childhood absence epilepsy. However, valproic acid is associated with greater attentional dysfunction, indicating that ethosuximide is the more appropriate initial therapy for this seizure disorder.

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