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The Effect of Clozapine on Hematological Indices: A 1-Year Follow-Up Study
Jimmy Lee1, Hiroyoshi Takeuchi, Gagan Fervaha
1From the *Department of General Psychiatry 1, Institute of Mental Health; †Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore; ‡Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; §Department of Neuropsychiatry, Keio University, School of Medicine, Tokyo, Japan; ∥Institute of Medical Science, University of Toronto; ¶Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; #Division of Clinical Pharmacology, Indiana University School of Medicine; **Indiana Clinical and Translational Sciences Institute, Indianapolis, IN; ††Campbell Family Mental Health Research Institute; and ‡‡Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Insights
Clozapine treatment for schizophrenia can cause temporary changes in blood cell counts, including white blood cells and platelets. These early hematological aberrations are usually transient and do not warrant discontinuing clozapine therapy.
Area of Science:
- Hematology
- Psychiatry
- Pharmacology
Background:
- Clozapine is a critical antipsychotic for treatment-resistant schizophrenia.
- Mandatory hematological monitoring is required due to potential adverse effects like agranulocytosis.
- Other hematological aberrations can lead to treatment discontinuation.
Purpose of the Study:
- To investigate the impact of clozapine on red blood cells, platelets, and white blood cells (WBCs) and their differentials.
- To analyze the trajectories of these cell counts during clozapine treatment.
- To understand the immunomodulatory effects of clozapine on hematopoiesis.
Main Methods:
- Retrospective analysis of complete blood counts from patients initiated on clozapine.
- Inclusion criteria: pre-clozapine CBC and 1-year follow-up.
- Extraction and plotting of red blood cells, platelets, WBCs, and differential counts (neutrophils, lymphocytes, monocytes, eosinophils, basophils).
Main Results:
- 101 patients included; 66 completed 1 year of treatment.
- Transient increases observed in WBCs, neutrophils, monocytes, eosinophils, basophils, and platelets within the first week.
- No agranulocytosis cases; five patients developed neutropenia, preceded by a neutrophil spike in three.
- Cumulative incidence: 48.9% neutrophilia, 5.9% eosinophilia, 3% thrombocytosis, 3% thrombocytopenia.
Conclusions:
- Early hematological aberrations occur across various cell lines, particularly myeloid lineage, during clozapine treatment.
- These disturbances are transient and likely linked to clozapine's immunomodulatory properties.
- Observed aberrations do not necessitate clozapine discontinuation.
Abstract:
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and is linked to a need for mandatory hematological monitoring. Besides agranulocytosis, other hematological aberrations have resulted in premature termination in some cases. Considering clozapine's role in immunomodulation, we proceeded to investigate the impact of clozapine on the following 3 main hematological cell lines: red blood cells, platelets, white blood cells (WBCs), and its differential counts. Data were extracted from patients initiated on clozapine between January 2009 and December 2010 at a single hospital. Patients with a preclozapine complete blood count, who were receiving clozapine during the 1-year follow-up period, were included in the present investigation. Counts of red blood cells, platelets, WBC, and its differential including neutrophils, lymphocytes, monocytes, eosinophils, and basophils were extracted and trajectories plotted. One hundred one patients were included in this study and 66 remained on clozapine at the end of 1 year. There was a synchronized but transient increase in WBC, neutrophils, monocytes, eosinophils, basophils, and platelets beginning as early as the first week of clozapine treatment. There were no cases of agranulocytosis reported in this sample, and five developed neutropenia. A spike in neutrophils immediately preceded the onset of neutropenia in three of the five. The cumulative incidence rates were 48.9% for neutrophilia, 5.9% for eosinophilia, and 3% each for thrombocytosis and thrombocytopenia. Early hematological aberrations are visible across a range of cell lines, primarily of the myeloid lineage. These disturbances are transient and are probably related to clozapine's immunomodulatory properties. We do not suggest discontinuing clozapine as a consequence of the observed aberrations.
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