Article ; Online: Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.
2023
Abstract: Introduction: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil ... ...
| Abstract | Introduction: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. Methods: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. Results: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm Conclusion: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN. |
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| Language | English |
| Publishing date | 2023-08-24 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 639422-x |
| ISSN | 1573-2509 ; 0920-9964 |
| ISSN (online) | 1573-2509 |
| ISSN | 0920-9964 |
| DOI | 10.1016/j.schres.2023.08.002 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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