Tolerance to antiepileptic drug effects. Experimental evidence and clinical significance

The development of tolerance to the anticonvulsant effect of drugs has been demonstrated in animal experiments for most antiepileptic drugs. This evidence is reviewed, including the methodological approach and the differentiation into 'metabolic' and 'functional' tolerance. Clinical evidence of the development to antiepileptic drug effects is equivocal: The existence of tolerance is generally accepted for the benzodiazepines which often lose their antiepileptic effect during prolonged treatment. For this group of drugs tolerance is a major clinical problem. With other antiepileptic drugs some degree of tolerance may develop, but this can hardly be recognized as such under clinical conditions, and is thus not considered to be of major importance for treatment of epilepsy.