[Hematologic effects of clozapine: a review of the international experience]

Before clozapine was marketed, 4 cases of agranulocytosis occurred amongst the 2,900 patients exposed to the drug in the clinical studies from 1962 to 1972. At that time, the frequency of 0.14% was considered comparable to that published with some phenothiazines. After clozapine was launched in different countries, several notifications of agranulocytosis/granulocytopenia were reported, with a high mortality ratio in some countries. This outbreak of agranulocytosis has led to the implementation of recommendations, particularly a strict worldwide hematologic surveillance with a discontinuation of clozapine when the white blood cells drop below a critical level. This article emphasizes the positive impact of these precautionary measures on the present incidence of the agranulocytosis and on the mortality ratio.