Paradoxical intoxication--a complication of anticonvulsant administration.

A new syndrome, paradoxical intoxication, has been defined in which high levels of hydantoins, and in one instance carbamazepine, produced an increase in seizures with little or no evidence of intoxication; a decrease in these levels produced an improvement in seizure control. This syndrome occurs often but not exclusively in those people who are less astute in assessing their neurologic status and therefore may experience unexpectedly higher blood levels of their anticonvulsants. Instances have been documented with serum levels above 40 mugm/ml for phenytoin or mephenytoin alone, or above 50 mugm/ml of combined hydantoins phenytoin and mephenytoin, and when the level is in the range of 20 mugm/ml and above for carbamazepine. Possible mechanisms underlying the syndrome are reviewed. Appropriate therapy is a reduction of the dose of the drug in question.