Agranulocytosis: incidence and risk factors

The use of clozapine has been limited by the risk of agranulocytosis. The cumulative incidence of agranulocytosis is 0.80% after 1 year and 0.91% after 1 1/2 years. Risk is greatest during the first 3 months of treatment and greater among women and the elderly. White-cell counts tend to spike upward before the occurrence of agranulocytosis. The occurrence of a white-cell count spike of > or = 15% above the previous count predicts development of agranulocytosis within 75 days (risk ratio = 3.02; 95% confidence interval, 1.38-6.57). Our results indicate that hematologic monitoring is necessary and effective. They also suggest that the frequency of monitoring could be reduced after the initial period of maximal risk.