Over a 3-year period, we encountered 6 adults whose seizure control unexpectedly deteriorated with the occurrence of partial
status epilepticus and daily multiple
seizures. Analysis of the case histories and subsequent clinical follow-up for 1 1/2 to 3 years disclosed the following evidence that demonstrates the role of
carbamazepine-epoxide in the development of the seizure exacerbation: (1) There were high serum
carbamazepine-epoxide concentrations while serum
carbamazepine concentrations were lower than or the same as baseline levels; (2) all patients were taking drugs that are known to increase serum
carbamazepine-epoxide concentrations; (3)
status epilepticus failed to respond to intravenous
phenytoin loading; (4) seizure exacerbation in all patients was corrected by withholding
carbamazepine dose; (5) seizure exacerbation recurred in 1 patient who resumed the same dose of
carbamazepine; and (6) there were no prior
status epilepticus or daily multiple
seizures despite previous toxicities with other
antiepileptic drugs in 3 patients. Our experience shows that inconspicuous elevation of
carbamazepine-epoxide levels during polytherapy may precipitate a distinct state of
drug toxicity characterized by severe exacerbation of
seizures.
Mental retardation may be a predisposition to this condition.