Ana Teresa Caliman-Fontes

Ary Gadelha

Gustavo C. Leal

Lucas C. Quarantini

Brazilian Journal of Psychiatry

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4 Dalgalarrondo P. Psicopatologia e semiologia dos transtornos men-tais. 3rd ed. Porto Alegre: Artmed; 2019.5 Cheniaux Jr E. Manual de psicopatologia. 6th ed. Rio de Janeiro:Guanabara Koogan; 2020.6 Chisolm MS. Putting the person back into psychiatry. 2021.https://www.psychiatrictimes.com/view/putting-the-person-back-into-psychiatryDiscussing clozapineadverse effects andmonitoring strategies:a focus on ethnic diversityBraz J Psychiatry. 2023 Sep-Oct;45(5):461-462doi:10.47626/1516-4446-2023-328900000000-0002-7316-1185We read with great interest the article by Goldani et al.,1which found that clozapine did not increase neutropeniarisk in a sample of 5,847 psychiatric patients – 1,038 onclozapine – from Hospital de Clı́nicas de Porto Alegre.The study design was retrospective; data were collectedfrom electronic medical records (EMR). Cox regressionanalysis identified ethnicity (specifically non-Hispanicwhite) and absolute neutrophil count (ANC) 4 2,000/mLduring the first year of monitoring as protective factorsagainst neutropenia. Presence of severe medical condi-tions was a risk factor, while clozapine use was not.These data hold considerable significance; nonetheless,we have some concerns about the conclusions drawntherefrom.First, we have reservations about its external validity toinform updates of nationwide monitoring strategies. PortoAlegre is the capital of Rio Grande do Sul, a southernstate of Brazil, with most of its population descendingfrom European immigrants. More than 85% of the Goldaniet al. sample comprised white non-Hispanics. This is notrepresentative of the Brazilian population – with only 43%of white ethnicity and over 50% of self-declared black ormixed ethnicity according to the last national survey,conducted in 20212 –, which could lead to bias, such as adifferent incidence of benign ethnic neutropenia (BEN).BEN is knowingly associated with African, Arabian andMediterranean ancestry, and could potentially lead tolower ANC at baseline and/or after treatment initiation.3The absolute risk of low ANC consistently showedhigher numerical values in the clozapine group. Limita-tions related to study design – retrospective, EMR-based –and power should be taken into account when interpretingthe results as a lack of association between clozapine andmoderate neutropenia. We have concerns over thepossible clinical translation to psychiatric practice of suchstatements.Despite these issues, we agree with the article’sfundamental conclusions. Agranulocytosis is indeed arelatively infrequent adverse event – with a reportedincidence of 0.9%4 – and excessive precaution should notpreclude the prescription of clozapine to patients in need.In a recent review of monitoring strategies worldwide,countries with the highest rates of clozapine usage5 wereamong those with the least stringent monitoring guide-lines.6 These findings reinforce the idea that modifyingmonitoring strategies could enhance access to clozapinetreatment.On the other extreme, there have been claims thatmonitoring should be restricted to the first months ofclozapine administration.4 Against this suggestion standsevidence that, though less frequent, late-onset hemato-logical effects of clozapine should still be a concern, withlittle more than 10% of agranulocytosis occurring after thesecond year of treatment.7Taking all this into account, we support evidence-basedflexibilizations of the monitoring strategy to improveaccessibility and prescription of clozapine to at-riskpopulations, while acknowledging the risk of neutropeniaarising from this prescription. In this regard, we believethat additional data from a more ethnically representativesample of the diverse Brazilian population is needed tosupport more generalizable treatment monitoring guide-lines – which should also consider specificities whendefining ANC thresholds, such as for patients with BEN.Ana Teresa Caliman-Fontes,1,20000-0000-0000-0000 Gustavo C. Leal,1,2Ary Gadelha,30000-0000-0000-0000 Lucas C. Quarantini1,20000-0000-0000-00001Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria,Hospital Universitário Professor Edgard Santos, UniversidadeFederal da Bahia, Salvador, BA, Brazil. 2Programa de Pós-Graduação em Medicina e Saúde, Faculdade de Medicina da Bahia,Universidade Federal da Bahia, Salvador, BA, Brazil. 3Departamentode Psiquiatria, Universidade Federal de São Paulo, São Paulo,SP, Brazil.Submitted Jul 12 2023, accepted Aug 16 2023.DisclosureAG has been a consultant and/or advisor to or hasreceived honoraria from Aché, Daiichi Sankyo, Torrent,Bayer, Cristália, and Janssen. LCQ has received con-sulting fees from Allergan, Abbot, Janssen Pharmaceu-ticals, and Lundbeck. The other authors report noconflicts of interest.How to cite this article: Caliman-Fontes AT, Leal GC,Gadelha A, Quarantini LC. Discussing clozapine adverseeffects and monitoring strategies: a focus on ethnicdiversity. Braz J Psychiatry. 2023;45:461-462. http://doi.org/10.47626/1516-4446-2023-3289References1 Goldani AAS, Rabelo-Da-ponte FD, Feiten JG, Lobato MIR, Bel-monte-De-Abreu PS, Gama CS. Risk of neutropenia among cloza-pine users and non-users: results from 5,847 patients. Braz JPsychiatry. 2022;44:21-5.2 Instituto Brasileiro de Geografia e Estatı́stica (IBGE). PesquisaNacional por Amostra de Domicı́lios (PNAD) Contı́nua: caracter-ı́sticas gerais dos moradores 2020-2021 [Internet]. 2022 [cited 2023Braz J Psychiatry. 2023;45(5)Letters to the Editors 461Oct 16]. www.ibge.gov.br/estatisticas/sociais/trabalho/17270-pnad-continua.html3 Manu P, Sarvaiya N, Rogozea LM, Kane JM, Correll CU. Benignethnic neutropenia and clozapine use: a systematic review of theevidence and treatment recommendations. J Clin Psychiatry.2016;77:e909-16.4 Myles N, Myles H, Xia S, Large M, Kisely S, Galletly C, et al. Meta-analysis examining the epidemiology of clozapine-associated neu-tropenia. Acta Psychiatr Scand. 2018;138:101-9.5 Bachmann CJ, Aagaard L, Bernardo M, Brandt L, Cartabia M,Clavenna A, et al. International trends in clozapine use: a study in17 countries. Acta Psychiatr Scand. 2017;136:37-51.6 Oloyede E, Blackman G, Whiskey E, Bachmann C, Dzahini O, ShergillS, et al. Clozapine haematological monitoring for neutropenia: a globalperspective. Epidemiol Psychiatr Sci. 2022;31:e83.7 Lahdelma L, Appelberg B. Clozapine-induced agranulocytosis inFinland, 1982-2007: long-term monitoring of patients is still war-ranted. J Clin Psychiatry. 2012;73:837-42.Braz J Psychiatry. 2023;45(5)462 Letters to the Editors

Discussing clozapine adverse effects and monitoring strategies: a focus on ethnic diversity

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Discussing clozapine adverse effects and monitoring strategies: a focus on ethnic diversity

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