The quality of evidence is downgraded by imprecise results (few patients and outcome events).
A Cochrane review [Abstract] 1 included 8 studies with a total of 691 children/adolescents. Seven studies recruited less than 50 participants. One study compared lamotrigine with placebo, 3 compared ethosuximide with valproate, 3 compared lamotrigine with valproate, and 1 compared ethosuximide, valproate, and lamotrigine. Meta-analysis was not performed due to the differing methodologies used in the studies.
One large (n=453) randomised, parallel double-blind controlled trial comparing ethosuximide, lamotrigine and sodium valproate in children with newly diagnosed childhood absence epilepsy found that at 12 months, seizure freedom was higher in patients taking ethosuximide (70/154, 45%) than in patients taking lamotrigine (31/146, 21%, p < 0.001), with no difference between valproate (64/146, 44%) and ethosuximide (70/154, 45%, p > 0.05).
The frequency of treatment failures due to intolerable adverse events was significantly different among the treatment groups, with the largest proportion of adverse events in the valproic acid group (48/146, 33%) compared to the ethosuximide (38/154, 25%) and the lamotrigine (29/146, 20%) groups (p < 0.037).
With regards to both efficacy and tolerability, ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures. However, if absence and generalised tonic-clonic seizures co-exist, valproate should be preferred, as ethosuximide is probably inefficacious on tonic-clonic seizures.
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