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Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy
Tracy A Glauser1, Avital Cnaan, Shlomo Shinnar
1Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA. tracy.glauser@cchmc.org
Insights
Ethosuximide and valproic acid are more effective for childhood absence epilepsy than lamotrigine. Ethosuximide offers better attentional tolerability, making it a preferred choice for pediatric epilepsy treatment.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Childhood absence epilepsy (CAE) is the most common pediatric epilepsy syndrome.
- Standard treatments include ethosuximide, valproic acid, and lamotrigine.
- Optimal first-line empirical treatment for CAE remains undefined.
Purpose of the Study:
- To compare the efficacy and tolerability of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed CAE.
- To evaluate the neuropsychological effects, specifically attentional dysfunction, associated with each treatment.
Main Methods:
- A double-blind, randomized, controlled clinical trial involving 453 children with newly diagnosed CAE.
- Incremental dose adjustments were made to achieve seizure freedom, maximal tolerable dose, or avoid treatment failure.
- Primary outcome was freedom from treatment failure at 16 weeks; secondary outcome was attentional dysfunction.
Main Results:
- Ethosuximide and valproic acid demonstrated similar and superior efficacy (53% and 58% freedom-from-failure rates) compared to lamotrigine (29%).
- No significant differences were observed in drug discontinuation rates due to adverse events among the three medications.
- Attentional dysfunction was more prevalent with valproic acid (49%) than ethosuximide (33%).
Conclusions:
- Ethosuximide and valproic acid are more effective first-line treatments for childhood absence epilepsy than lamotrigine.
- Ethosuximide is associated with fewer adverse effects on attention compared to valproic acid.
- These findings guide the selection of initial empirical therapy for pediatric absence epilepsy.
Background:
Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.
Methods:
In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons.
Results:
The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03).
Conclusions:
Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)
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