Phenytoin-induced seizures: a paradoxical effect at toxic concentrations in epileptic patients

We examined the incompletely defined convulsant action of phenytoin (PHT) at toxic concentrations in humans. A retrospective chart review (1979-1985) yielded 96 cases (90 patients), meeting both clinical and laboratory criteria for PHT intoxication. Seven patients, all with epilepsy, had one or more seizures while toxic. However, in only two patients (2.1%) with serum concentrations of 93.2 and 69.7 micrograms/ml was a causal relationship deemed highly probable. Seizures did not occur in most toxic epileptic patients with total serum PHT concentrations as high as 85.1 micrograms/ml or in any of the nonepileptic patients with concentrations as high as 64.2 micrograms/ml. The lack of convulsant action of PHT in these patients suggests that seizure risk may be multifactorial and also that PHT is a weak convulsant. We conclude that PHT at very high concentrations can rarely exacerbate seizures or even precipitate generalized status in some epileptic patients, a paradoxical effect.