Soon after clinical studies of clozapine were initiated— more than 25 years ago—it was apparent that the drug was at least as effective as available neuroleptics and resulted in negligible extrapyramidal side effects. It was hoped that the widespread availability of the drug would represent a major innovation in the treatment of schizophrenia. These hopes were dealt a severe blow when the drug was found to be associated with a relatively high rate of agranulocytosis. This resulted in the drug being severely restricted in its use in some countries and unavailable in others (including the United States, where it has been given to only a limited number of patients under humanitarian use protocols or in carefully monitored investigations).
Because of this toxic effect, the Food and Drug Administration requested data indicating that clozapine is more See also p 789. effective than conventional neuroleptics in patients considered resistant to treatment. This