Ethosuximide (ESM) is used commonly as a first-line therapy for typical absence seizures occurring in primary generalized epilepsy syndromes. However, atypical absence is more common in the developmentally disabled population. Although ESM may be effective against atypical absence, the common association with other seizures (e.g., atonic, myoclonic, generalized tonic-clonic) that do not respond to ESM renders it a less-than-optimal choice for treating such patients.

Although ESM usually is considered a benign treatment for absence seizures in primary generalized epilepsies, it can cause:

  • confusion
  • sleep disturbances
  • assorted behavioral changes (e.g., aggression, depression, hostility, and even psychosis33)

The controversial entity of "forced normalization"45 has been invoked as a potential explanation for ESM-related behavioral abnormalities, in which ESM-induced "normalization" of the EEG recording results in a paradoxical behavioral abnormality.46

Adapted from: Ettinger AB, Barr WB, and Solomon SP. Psychotropic properties of antiepileptic drugs in patients with developmental disabilities. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;219–230. With permission from Elsevier (

Authored By: 
Sanford P. Solomon MD
William B. Barr MD
Alan B. Ettinger MD
Reviewed By: 
Steven C. Schachter MD
Thursday, April 1, 2004