Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom

Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Methods: Here, an international group of collaborators discusses a point of view complementary to...

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Autores: León, José de, Arrojo Romero, Manuel, Verdoux, Hélène, Ruan, Can-Jun, Schoretsanitis, Georgios, Rohde, Christopher, Cohen, Dan, Schulte, Peter F. J., Kim, Se Hyun, Cotes, Robert O., Leung, Jonathan G., Otsuka, Yuji, Kirilochev, Oleg O., Baptista, Trino, Grover, Sandeep, Every-Palmer, Susanna, Clark, Scott R., McGrane, Ian R., Motuca, Mariano, Olmos, Ismael, Wilkowska, Alina, Sagud, Marina, Yağcioğlu, A Elif Anil, Ristic, Dragana Ignjatovic, Lazary, Judit, Sanz Álvarez, Emilio José, Cuevas Castresana, Carlos de las
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de La Laguna (ULL)
Repositorio:RIULL. Repositorio Institucional de la Universidad de La Laguna
OAI Identifier:oai:riull.ull.es:915/39637
Acceso en línea:http://riull.ull.es/xmlui/handle/915/39637
Access Level:acceso abierto
Palabra clave:lozapine/adverse effects
clozapine/administration and dosage
clozapine/metabolism
clozapine/therapeutic use
clozapine/toxicity
Covid-19
drug labeling
infection
inflammation
mortality/drug effects
pneumonia
schizophrenia
sex
smoking
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spelling Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United KingdomLeón, José deArrojo Romero, ManuelVerdoux, HélèneRuan, Can-JunSchoretsanitis, GeorgiosRohde, ChristopherCohen, DanSchulte, Peter F. J.Kim, Se HyunCotes, Robert O.Leung, Jonathan G.Otsuka, YujiKirilochev, Oleg O.Baptista, TrinoGrover, SandeepEvery-Palmer, SusannaClark, Scott R.McGrane, Ian R.Motuca, MarianoOlmos, IsmaelWilkowska, AlinaSagud, MarinaYağcioğlu, A Elif AnilRistic, Dragana IgnjatovicLazary, JuditSanz Álvarez, Emilio JoséCuevas Castresana, Carlos de laslozapine/adverse effectsclozapine/administration and dosageclozapine/metabolismclozapine/therapeutic useclozapine/toxicityCovid-19drug labelinginfectioninflammationmortality/drug effectspneumoniaschizophreniasexsmokingPurpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. Findings/results: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. Implications/conclusions: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.Medicina Interna, Dermatología y PsiquiatríaAdherencia Terapéutica202420242023info:eu-repo/semantics/articleapplication/pdfhttp://riull.ull.es/xmlui/handle/915/39637reponame:RIULL. Repositorio Institucional de la Universidad de La Lagunainstname:Universidad de La Laguna (ULL)InglésJournal of Clinical Psychopharmacology 2023 May-Jun;43(3)Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ESoai:riull.ull.es:915/396372026-06-22T13:13:57Z
dc.title.none.fl_str_mv Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
title Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
spellingShingle Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
León, José de
lozapine/adverse effects
clozapine/administration and dosage
clozapine/metabolism
clozapine/therapeutic use
clozapine/toxicity
Covid-19
drug labeling
infection
inflammation
mortality/drug effects
pneumonia
schizophrenia
sex
smoking
title_short Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
title_full Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
title_fullStr Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
title_full_unstemmed Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
title_sort Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom
dc.creator.none.fl_str_mv León, José de
Arrojo Romero, Manuel
Verdoux, Hélène
Ruan, Can-Jun
Schoretsanitis, Georgios
Rohde, Christopher
Cohen, Dan
Schulte, Peter F. J.
Kim, Se Hyun
Cotes, Robert O.
Leung, Jonathan G.
Otsuka, Yuji
Kirilochev, Oleg O.
Baptista, Trino
Grover, Sandeep
Every-Palmer, Susanna
Clark, Scott R.
McGrane, Ian R.
Motuca, Mariano
Olmos, Ismael
Wilkowska, Alina
Sagud, Marina
Yağcioğlu, A Elif Anil
Ristic, Dragana Ignjatovic
Lazary, Judit
Sanz Álvarez, Emilio José
Cuevas Castresana, Carlos de las
author León, José de
author_facet León, José de
Arrojo Romero, Manuel
Verdoux, Hélène
Ruan, Can-Jun
Schoretsanitis, Georgios
Rohde, Christopher
Cohen, Dan
Schulte, Peter F. J.
Kim, Se Hyun
Cotes, Robert O.
Leung, Jonathan G.
Otsuka, Yuji
Kirilochev, Oleg O.
Baptista, Trino
Grover, Sandeep
Every-Palmer, Susanna
Clark, Scott R.
McGrane, Ian R.
Motuca, Mariano
Olmos, Ismael
Wilkowska, Alina
Sagud, Marina
Yağcioğlu, A Elif Anil
Ristic, Dragana Ignjatovic
Lazary, Judit
Sanz Álvarez, Emilio José
Cuevas Castresana, Carlos de las
author_role author
author2 Arrojo Romero, Manuel
Verdoux, Hélène
Ruan, Can-Jun
Schoretsanitis, Georgios
Rohde, Christopher
Cohen, Dan
Schulte, Peter F. J.
Kim, Se Hyun
Cotes, Robert O.
Leung, Jonathan G.
Otsuka, Yuji
Kirilochev, Oleg O.
Baptista, Trino
Grover, Sandeep
Every-Palmer, Susanna
Clark, Scott R.
McGrane, Ian R.
Motuca, Mariano
Olmos, Ismael
Wilkowska, Alina
Sagud, Marina
Yağcioğlu, A Elif Anil
Ristic, Dragana Ignjatovic
Lazary, Judit
Sanz Álvarez, Emilio José
Cuevas Castresana, Carlos de las
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina Interna, Dermatología y Psiquiatría
Adherencia Terapéutica
dc.subject.none.fl_str_mv lozapine/adverse effects
clozapine/administration and dosage
clozapine/metabolism
clozapine/therapeutic use
clozapine/toxicity
Covid-19
drug labeling
infection
inflammation
mortality/drug effects
pneumonia
schizophrenia
sex
smoking
topic lozapine/adverse effects
clozapine/administration and dosage
clozapine/metabolism
clozapine/therapeutic use
clozapine/toxicity
Covid-19
drug labeling
infection
inflammation
mortality/drug effects
pneumonia
schizophrenia
sex
smoking
description Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. Findings/results: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. Implications/conclusions: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://riull.ull.es/xmlui/handle/915/39637
url http://riull.ull.es/xmlui/handle/915/39637
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Clinical Psychopharmacology 2023 May-Jun;43(3)
dc.rights.none.fl_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
rights_invalid_str_mv Licencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIULL. Repositorio Institucional de la Universidad de La Laguna
instname:Universidad de La Laguna (ULL)
instname_str Universidad de La Laguna (ULL)
reponame_str RIULL. Repositorio Institucional de la Universidad de La Laguna
collection RIULL. Repositorio Institucional de la Universidad de La Laguna
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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