« Back

Comparison of common treatment regimens for childhood absence epilepsy favors ethosuximide as first-line therapy

Wednesday, March 17 2010 | Comments

---

What's This? Ethosuximide and valproic acid seem to be more effective than lamotrigine as treatments for newly diagnosed childhood absence epilepsy, and ethosuximide is associated with fewer adverse effects on attention than valproic acid is, according to findings from a randomized, double-blind trial.

The trial compared the efficacy, tolerability, and neuropsychological effects of the 3 drugs in 453 children with newly diagnosed childhood absence epilepsy. During 16 weeks of treatment, the doses of the drugs were increased until seizure freedom was achieved or side effects limited dose escalation. The highest allowable daily doses were 60 mg/kg of ethosuximide, 60 mg/kg of valproic acid, and 12 mg/kg of lamotrigine (up to 2,000 mg/d, 3,000 mg/d, and 600 mg/d, respectively).

The primary outcome measure was freedom from treatment failure after 16 weeks of therapy. Reasons for treatment failure included a lack of seizure control, intolerable adverse effects and withdrawal from the study. During the trial, the presence of seizures was assessed every 4 weeks with parental reports, trials of bedside hyperventilation, and 1-hour video electroencephalogram recordings.

The data showed that 53% of the ethosuximide group, 58% of the valproic acid group, and 29% of the lamotrigine group achieved freedom from treatment failure during the trial. Relative to lamotrigine, the odds ratio (OR) for freedom from treatment failure was 2.66 (95% CI, 1.65-4.28; P<.001) with ethosuximide and 3.34 (95% CI, 2.06-5.42; P<.001) with valproic acid. There was no significant difference between ethosuximide and valproic acid in the primary outcome measure.

The persistence of seizures was more common with lamotrigine (47%) than with valproic acid (12%) or ethosuximide (14%; P<.001 for both comparisons), but there were no significant differences among the 3 drugs in discontinuations because of adverse effects.

The secondary outcome measure of the trial was attentional dysfunction, defined as a Confidence Index of >=0.6 on the Conners' Continuous Performance Test.

Results for the secondary outcome measure showed that attentional dysfunction was more common with valproic acid (49%) than with ethosuximide (33%; OR, 1.95 [1.12-3.41]; P=.03) or lamotrigine (24%; OR, 3.04 [95% CI, 1.69-5.49]; P<.001), but there was no significant difference between ethosuximide and lamotrigine. The differences between valproic acid and ethosuximide and between valproic acid and lamotrigine remained significant even after adjustment for differences in baseline Confidence Index scores (P<.001 for both comparisons).

"These results suggest that ethosuximide, one of the oldest available antiseizure medications, is a sensible choice for initial empirical monotherapy in childhood absence epilepsy," the authors concluded. (Glauser TA, et al. N Engl J Med 2010;362:790-799.)

Print  |  E-mail