Does switching to another antipsychotic in patients with clozapine-associated granulocytopenia solve the problem? Case series of 18 patients.

Unlabelled: Clozapine is a well-known drug that is used in treatment-resistant schizophrenia, but granulocytopenia, which may lead to a potentially fatal condition such as agranulocytosis, limit its use. The question about which antipsychotic should be used after a diagnosis of clozapine-associated granulocytopenia is difficult to answer, because antipsychotics other than clozapine may also have hematologic toxicity, or they may prolong clozapine-associated granulocytopenia. In this study, we aimed to find out the incidence of clozapine-associated granulocytopenia in our treatment sample and discuss suitable antipsychotic drug options in terms of hematologic toxicity, for management of clozapine-associated granulocytopenia.

Subjects: One thousand five hundred twenty-four schizophrenia patients, treated with clozapine, were included in the study.

Methods: Patients' white blood cell counts were monitored closely. Should granulocytopenia related to clozapine be diagnosed, clozapine was stopped immediately, and a new antipsychotic that the patient did not have a history of use was begun, according to the clinical profile of the patient. Persistent low white blood cell count after the 10th day of cessation of clozapine was accepted as prolongation effect.

Results: Of the 1524 schizophrenia patients, 18 were diagnosed to have granulocytopenia, which means that 1.18% of the clozapine users developed granulocytopenia related to clozapine. Six of the patients were treated with olanzapine, 5 patients were treated with quetiapine, 1 patient was treated with risperidone, and 6 patients were treated with amisulpride after clozapine is stopped. None of the patients treated with risperidone or amisulpride showed prolonged low white blood cell count. Two of the patients treated with olanzapine (33.3%) and 2 of the patients treated with quetiapine (40.0%) showed prolonged leukopenia.

Discussion: It is noteworthy that 33.3% of the patients treated with olanzapine and 40.0% of the patients treated with quetiapine showed prolonged leukopenia. This finding is also consistent with the literature that declares higher numbers of cases about prolongation of clozapine-associated granulocytopenia for olanzapine and quetiapine than risperidone and amisulpride. After switching to another antipsychotic drug, close monitoring of white blood cell count on a daily basis for the first 2 weeks should be continued until white blood cell counts are stabilized. Quetiapine and olanzapine especially need attention after clozapine-associated granulocytopenia. Further studies with larger series and longer follow-up should be carried out.