The Taking of Absence Epilepsy One Two Three

The most common, identifiable form of pediatric epilepsy, absence seizures (formerly known as petit mal seizures) were first described in the early 18th century by (you guessed it) a French guy. Effective and relatively safe pharmacologic treatment for the condition has been available since 1960, when ethosuximide (Zarontin) was introduced by Parke-Davis (now a subsidiary of Pfizer, like just about every other drug company).

Absence seizures are also responsive to valproic acid (aka Depakene or Depakote; Abbott), which was FDA approved for treatment of the disorder in 1978, and lamotrigine (Lamictal; GSK), which has been studied for the treatment of absence seizures since at least the late 1990s.*

Despite our extensive clinical experience with these drugs, it was unknown which provided the best empirical therapy for absence epilepsy. In fact, Glauser and other neurologists at the University of Cincinnati concluded in 2006 that it was "impossible to develop an evidence-based guideline" for the initial, monotherapy treatment of generalized seizures and specifically those in children, because of the "alarming lack of well-designed, properly conducted" randomized, controlled trials. This finding evidently prompted Glauser and his colleagues to conduct a randomized, double-blind multicenter trial of the 3 drugs in children with newly diagnosed absence seizures—the results of which are available in today's issue of the NEJM.

Among 453 children with new-onset absence epilepsy, Glauser et al found that ethosuximide or valproic acid were significantly more likely to result in a primary composite outcome of seizure control and tolerability (~50%-60% of patients) than lamotrigine (~30% of patients) after 4 months. Attentional deficit, a secondary outcome measure, was significantly more likely with valproic acid than ethosuximide (49% vs 33%).

Commenting at MedPage Today, Glauser said, "[E]thosuximide gave the child the best chance to get the combination of seizure control without side effects or [adverse] effects on attention."

So ethosuximide, it is; then valproic acid; then lamotrigine.

* Although lamotrigine is not FDA approved for the treatment of absence seizures specifically.

The characteristic 3-per-second spike-and-wave EEG pattern of absence epilepsy from An Introduction to Epilepsy.