Nicholas Myles1,2, Hannah Myles3, Shelley Xia4, Matthew Large4,5, Robert Bird6,7, Cherrie Galletly3,8,9, Steve Kisely2,10, Dan Siskind2,11. 1. 1 Division of Haematology, SA Pathology, Adelaide, SA, Australia. 2. 2 School of Medicine, The University of Queensland, St Lucia, QLD, Australia. 3. 3 Discipline of Psychiatry, The University of Adelaide, Adelaide, SA, Australia. 4. 4 Department of Psychiatry, Prince of Wales Hospital, Kensington, NSW, Australia. 5. 5 School of Psychiatry, UNSW Sydney, Kensington, NSW, Australia. 6. 6 Division of Cancer Services, Princess Alexandra Hospital, Woolloongabba, QLD, Australia. 7. 7 School of Medicine, Griffith University, Nathan, QLD, Australia. 8. 8 Mental Health, Ramsay Health Care, Gilberton, SA, Australia. 9. 9 Department of Mental Health, Northern Adelaide Local Health Network, Elizabeth, SA, Australia. 10. 10 Departments of Psychiatry, Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada. 11. 11 Metro South Addiction and Mental Health Service, Woolloongabba, QLD, Australia.
Abstract
BACKGROUND: In most countries, clozapine can only be prescribed with regular monitoring of white blood cell counts because of concerns that clozapine has a stronger association with neutropenia than other antipsychotics. However, this has not been previously demonstrated conclusively with meta-analysis of controlled studies. METHODS: The aim of this study was to assess the strength of the association between clozapine and neutropenia when compared to other antipsychotic medications by a meta-analysis of controlled studies. An electronic search of Medline (1948-2018), PsycINFO (1967-2018) and Embase (1947-2018) using search terms (clozapine OR clopine OR clozaril OR zaponex) AND (neutropenia OR agranulocytosis) was undertaken. Random-effects meta-analysis using Mantel-Haenszel risk ratio was used to assess the strength of the effect size. RESULTS: We located 20 studies that reported rates of neutropenia associated with clozapine and other antipsychotic medications. The risk ratio was not significantly increased in clozapine-exposed groups compared to exposure to other antipsychotic medications (Mantel-Haenszel risk ratio = 1.45, 95% confidence interval = [0.87, 2.42]). This also applied to severe neutropenia (absolute neutrophil count < 500 per µL) when compared to other antipsychotics (Mantel-Haenszel risk ratio = 1.65, 95% confidence interval = [0.58, 4.71]). The relative risk of neutropenia associated with clozapine exposure was not significantly associated with any individual antipsychotic medication. CONCLUSION: Data from controlled trials do not support the belief that clozapine has a stronger association with neutropenia than other antipsychotic medications. This implies that either all antipsychotic drugs should be subjected to haematological monitoring or monitoring isolated to clozapine is not justified.
BACKGROUND: In most countries, clozapine can only be prescribed with regular monitoring of white blood cell counts because of concerns that clozapine has a stronger association with neutropenia than other antipsychotics. However, this has not been previously demonstrated conclusively with meta-analysis of controlled studies. METHODS: The aim of this study was to assess the strength of the association between clozapine and neutropenia when compared to other antipsychotic medications by a meta-analysis of controlled studies. An electronic search of Medline (1948-2018), PsycINFO (1967-2018) and Embase (1947-2018) using search terms (clozapine OR clopine OR clozaril OR zaponex) AND (neutropenia OR agranulocytosis) was undertaken. Random-effects meta-analysis using Mantel-Haenszel risk ratio was used to assess the strength of the effect size. RESULTS: We located 20 studies that reported rates of neutropenia associated with clozapine and other antipsychotic medications. The risk ratio was not significantly increased in clozapine-exposed groups compared to exposure to other antipsychotic medications (Mantel-Haenszel risk ratio = 1.45, 95% confidence interval = [0.87, 2.42]). This also applied to severe neutropenia (absolute neutrophil count < 500 per µL) when compared to other antipsychotics (Mantel-Haenszel risk ratio = 1.65, 95% confidence interval = [0.58, 4.71]). The relative risk of neutropenia associated with clozapine exposure was not significantly associated with any individual antipsychotic medication. CONCLUSION: Data from controlled trials do not support the belief that clozapine has a stronger association with neutropenia than other antipsychotic medications. This implies that either all antipsychotic drugs should be subjected to haematological monitoring or monitoring isolated to clozapine is not justified.
Authors: Dan Siskind; William G Honer; Scott Clark; Christoph U Correll; Alkomiet Hasan; Oliver Howes; John M Kane; Deanna L Kelly; Robert Laitman; Jimmy Lee; James H MacCabe; Nick Myles; Jimmi Nielsen; Peter F Schulte; David Taylor; Helene Verdoux; Amanda Wheeler; Oliver Freudenreich Journal: J Psychiatry Neurosci Date: 2020-07-01 Impact factor: 6.186
Authors: André Akira Sueno Goldani; Francisco Diego Rabelo-da-Ponte; Jacson Gabriel Feiten; Maria Ines R Lobato; Paulo S Belmonte-de-Abreu; Clarissa S Gama Journal: Braz J Psychiatry Date: 2022 Jan-Feb Impact factor: 2.697