Leukocytosis Associated with Clozapine Treatment: A Case Report

Abstract

Clozapine is considered the antipsychotic of choice for refractory schizophrenia because of its efficacy. The ongoing obstacles to clozapine treatment have been its risk for hematologic side effects and regular blood monitoring. The incidence of clozapine-induced hematologic adverse effects in clinical trials is neutropenia 3%, agranulocytosis 1%, eosinophilia 1%, and leukocytosis 1%. Clozapine-induced neutropenia and agranulocytosis have been investigated. However, leukocytosis, defined as a leukocyte count greater than 11,000 cells per mm, associated with clozapine treatment has received less attention in the literature. The clinical decision to continue or stop clozapine when leukocytosis develops could be challenging. Leukocytosis, which can occur within each of the white blood cell lines, can have multiple causes, including extreme stress and infection, and generally triggers a medical investigation for underlying causes. Medications can cause leukocytosis via demargination of leukocytes, via increased bone marrow production or release of stored cells, or via decreased leukocyte apoptosis. Clinical manifestations of drug-induced leukocytosis can include fever and malaise, but long-term sequelae are unclear. As such, there are no guidelines to advise clinicians if or when clozapine should be discontinued if leukocytosis appears. Moreover, there are no controlled data available to suggest antipsychotic treatment options if clozapine is discontinued because of associated hematologic side effects. This report illustrates a treatment-resistant patient who developed a neutrophilic leukocytosis up to 22.3 1000/mm during clozapine treatment. Clozapine was tapered and discontinued and subsequently the white blood count (WBC) returned to within the normal range. However, the patient became floridly psychotic after the discontinuation of clozapine. The rise of the WBC and absolute neutrophil count (ANC) counts steadily with