Psychiatric Complications of Absence Therapy and Their Relation to Alteration of Sleep

In the treatment of absence seizures, doctors have to choose mainly between two drugs: ethosuximide (ES) and sodium valproate (VPA). The situation is somewhat unusual in the field of epilepsy. There are two drugs of about equal efficiency (Simon and Penry, 1975) for about the same seizure types, but they are absolutely unrelated chemically; as similar as they are in their desired action, as much they differ in their possible side effects. With VPA, loss of hair, weight gain, tremor, thrombocytopenia, and rare but fatal instances of liver failure have been reported, and, more recently, there is suspicion of a teratogenic effect (Robert and Guibaud, 1982). With ES, no fatalities seem to have been reported, and singultus is one of the few common adverse effects. In quite a few patients, however, psychotic episodes have been observed, which were reviewed by Roger et al. (1968). As these occur at extremely different drug levels (Wolf, 1977) but are usually accompanied by complete or quasicomplete seizure control, they have been considered examples of “forced normalization” (Wolf and Trimble, in press)—an intriguing condition, the pathogenesis of which is still unexplained. This has not been observed with absence control by VPA (Wolf, 1976) even in patients that have had forced normalization with ES. Quantitative investigations of this difference have, however, not been reported, although they seem of considerable interest, as any significant difference between the drugs in this respect would be of high theoretical and practical importance.