Ethosuximide has been identified as the preferred initial therapy for pediatric patients with childhood absence epilepsy (CAE), according to the results of a recent National Institutes of Health-funded, double-blind, randomized trial published in Neurology.
The aim of the study (ClinicalTrials.gov identifier: NCT00088452) was to characterize pretreatment behavioral problems and differential effects of initial monotherapy medications in children with CAE. The Child Behavior Checklist (CBCL) — the primary measure of behavior — was administered at baseline, at weeks 16 to 20, and at month 12. On the CBCL, scores ≥70 are considered clinically significant. The comparative efficacy and tolerability of ethosuximide, lamotrigine, and valproic acid were examined in children with newly diagnosed CAE.
CBCL data were available for 382 participants at baseline, 310 participants at the week 16 to 20 visit, and 168 participants at the month 12 visit. The average patient age at study entry was 7.6±2.2 years.
At baseline, 8% of children with CAE had total problem scores ≥70 (mean score, 52.9±10.91; 95% CI, 6%-11%), 5% had internalizing problems ≥70 (95% CI, 3%-8%), 6% had externalizing problems ≥70 (95% CI, 4%-9%), 15% had attention problems ≥70 (95% CI, 12%-19%), and 7% had attention-deficit/hyperactivity problems ≥70 (95% CI, 4.5%-10%). The highest mean score (60.1±9.78) was reported with attention problems.
At the week 16 to 20 visit, patients treated with valproic acid had significantly higher mean total problems scores (51.7; 98.3% CI, 48.6-54.7) and a higher percentage of total problems scores ≥70 (10.6%; 98.3% CI, 4.6%-19.9%) compared with scores in the ethosuximide-treated patients (46.5; 98.3% CI, 43.4-49.5) and (1%; 98.3% CI, 0.0%-6.5%), respectively, and in lamotrigine-treated patients (48.8; 98.3% CI, 45.8-51.9) and (2.9%; 98.3% CI, 0.4%-9.5%), respectively (P =.0038 and P =.0032 for overall comparisons by χ2 and analysis of variance, respectively).
At the month 12 visit, participants taking valproic acid had significantly higher attention problems scores (57.9; 98.3% CI, 55.6-60.3) compared with those receiving ethosuximide (54.5; 95% CI, 52.1-56.9).
Based on these longitudinal behavioral assessments, the investigators identified an elevated rate of pretreatment behavioral issues in children with CAE. Study findings demonstrated a relationship between negative behaviors and ongoing seizures and attention problems.
Treatment with valproic acid was shown to be associated with worse behavioral outcomes compared with ethosuximide or lamotrigine. The researchers concluded that ethosuximide is the preferred initial monotherapy for pediatric patients with CAE.
Shinnar RC, Shinnar S, Cnaan A, et al; Childhood Absence Epilepsy Study Group. Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. Neurology. 2017;89(16):1698-1706.