Agranulocytosis during treatment with clozapine

Abstract

Within six months of the introduction of the new antipsychotic drug clozapine in Finalnd, 17 cases of neutropenia or agranulocytosis were recorded amongst about 3000 patients treated. Agranulocytosis was fatal in eight patients, and in addition, two patients developed thrombocytopenia, and one patient leukaemia. As additional cases might well have been overlooked as banal infections, the risk of developing agranulocytosis during clozapine treatment was at least 0.5%. Impaired elimination of the drug or increased susceptibility of granulocyte precursors to clozapine, possibly due to some inherited characteristic, might explain the high incidence of complications.

Population-Based Drug-Induced Agranulocytosis

“…The risk of agranulocytosis associated with ticlopidine 14 and clozapine 17,18 had already been uncovered in clinical trials.…”

Acute and subchronic effects of clozapine on licking in rats: tolerance to disruptive effects on number of licks, but no tolerance to rhythm slowing

“…Despite its tendency to induce agranulocytosis (Idanpaan-Heikkila et al 1977), the atypical neuroteptic clozapine is an effective psychotherapeutic agent in treatment-resistant schizophrenic patients (e.g., Meltzer 1992a); moreover, clozapine has a quite low incidence of inducing extrapyramidat side effects (Schmauss et al 1989;Meltzer 1992b). The therapeutic success of this drug has spurred the search for clozapine-like drugs without leukocytopenic side effects.…”

A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism

“…In addition to the well documented evidence associating neurological abnormalities with schizophrenia, there is some evidence that hematologic disturbances may be associated with genetic vulnerability to schizophrenia. Studies have shown that risk for clozapine-induced agranulocytosis may vary by ethnicity with rates for Finnish (12) and Jewish (13) populations being particularly elevated. Other investigators studying subjects from the Copenhagen schizophrenia high-risk project have hypothesized that disturbances in fetal neuronal development that are under genetic control may be associated with an increased vascular sensitivity to periventricular hemorrhage (14).…”