Hematological Effects | Cardiac Effects | Metabolic Effects | Seizures | Constipation | Other Side Effects
The side effects of clozapine make it one of the most challenging
medications for psychiatrists to prescribe. The main factor that
limits its use is the potential serious side effect of agranulocytosis.
Agranulocytosis is defined as a drop in absolute neutrophil count
(ANC) to levels below 500/mm3.
In 1975, there were 17 cases of agranulocytosis in Finland, and
widespread use of the medication for the treatment of schizophrenia
was temporarily halted (Amsler et al. 1977; de la Chapelle et al. 1977). Agranulocytosis is a potentially
lethal side effect that occurs in less than 1% of patients
treated in the United States (Alvir et al. 1993). In
the United States, all patients who are taking clozapine are entered
into a national registry. Through the national registry, patients
are prescribed the medication only if their WBC count shows no signs
of clinically meaningful suppression (Honigfeld 1996).
In a review of the morbidity and mortality of clozapine-treated
patients (Honigfeld et al. 1998) over a 5-year period,
99,502 patients were registered through the Clozaril National Registry.
Of these, 2,931 (2.95%) patients developed leukopenia (WBC
count = 3,500/mm3),
and 382 (0.38%) patients developed agranulocytosis (ANC <500/mm3).
Twelve of the cases of agranulocytosis (0.012%) were fatal.
These findings contrast with the 1%–2% cumulative
incidence expected from the premarketing experience with clozapine.
In the United States, 1,743 patients received the drug in premarketing
trials. In addition, this estimate was based on trials in Europe
performed in the 1970s and 1980s (Honigfeld et al. 1998).
The encouraging report by Honigfeld et al. (1998) supports
the monitoring system for clozapine as an adequate measure to prevent