It has now been reliably established that clozapine produces agranulocytosis in slightly less than 1 per 100 patients. (78> This is 15 to 30 times the rate associated with the phenothiazines and possibly higher than that for the butyrophenones. The peak of agranulocytosis with clozapine occurs between 4 and 18 weeks, and then falls off sharply. The incidence at various periods after 6 months has never been precisely calculated. Weekly monitoring of the white cell or absolute neutrophil count is required for 26 weeks in most countries, with the frequency decreasing to biweekly or monthly thereafter, sometimes on a voluntary basis. The cost-effectiveness of monitoring after a year has not been studied but it is probably in the range that would lead to its abandonment by current standards. With monitoring, agranulocytosis can usually be detected before infection sets in or becomes overwhelming. Discontinuation of clozapine, beginning treatment with colony cell stimulating factors, and the usual procedures for treating an infection are usually effective in restoring the white cell line.

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