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

被引：21

作者：

de Leon, Jose ^{[1
,2
,42
]}

Arrojo-Romero, Manuel ^{[3
]}

Verdoux, Helene ^{[4
]}

Ruan, Can-Jun ^{[5
,6
,7
]}

Schoretsanitis, Georgios ^{[8
,9
,10
]}

Rohde, Christopher ^{[11
,12
]}

Cohen, Dan ^{[13
,14
]}

Schulte, Peter F. J. ^{[13
,15
]}

Kim, Se Hyun ^{[16
]}

Cotes, Robert O. ^{[17
]}

Leung, Jonathan G. ^{[18
]}

Otsuka, Yuji ^{[19
]}

Kirilochev, Oleg O. ^{[20
]}

Baptista, Trino ^{[21
,22
,23
]}

Grover, Sandeep ^{[24
]}

Every-Palmer, Susanna ^{[25
,26
]}

Clark, Scott R. ^{[27
]}

McGrane, Ian R. ^{[28
]}

Motuca, Mariano ^{[29
]}

Olmos, Ismael ^{[30
,31
]}

Wilkowska, Alina ^{[32
]}

Sagud, Marina ^{[33
,34
]}

Yagcioglu, A. Elif Anil ^{[35
]}

Ristic, Dragana Ignjatovic ^{[36
]}

Lazary, Judit ^{[37
]}

Sanz, Emilio J. ^{[38
,39
]}

de Las Cuevas, Carlos ^{[40
,41
]}

机构：

[1] Eastern State Hosp, Mental Hlth Res Ctr, Lexington, KY USA

[2] Univ Basque Country, Santiago Apostol Hosp, Biomed Res Ctr Mental Hlth Net CIBERSAM, Vitoria, Spain

[3] Complejo Hosp Univ Santiago, Dept Psychiat, Santiago De Compostela, Spain

[4] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, Team Pharmacoepidemiol, Inserm,UMR 1219, F-33000 Bordeaux, France

[5] Capital Med Univ, Lab Clin Psychopharmacol, Beijing, Peoples R China

[6] Capital Med Univ, Beijing Anding Hosp, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China

[7] Capital Med Univ, Beijing Anding Hosp, Beijing Key Lab Mental Disorders, Beijing, Peoples R China

[8] Univ Zurich, Psychiat Hosp, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland

[9] Northwell Hlth, Zucker Hillside Hosp, Psychiat Res, Glen Oaks, NY USA

[10] Zucker Sch Med Northwell Hofstra, Dept Psychiat, Hempstead, NY USA

[11] Aarhus Univ Hosp Psychiat, Dept Affect Disorders, Aarhus, Denmark

[12] Aarhus Univ, Dept Clin Med, Aarhus, Denmark

[13] Dutch Clozapine Collaborat Grp, Castricum, Netherlands

[14] Mental Hlth Serv North Holland North, Dept Severe Mental Illness, FACT Team Heerhugowaard, Alkmaar, Netherlands

[15] Mental Hlth Serv Noord Holland Noord, Mental Hlth Team Alkmaar, Alkmaar, Netherlands

[16] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Psychiat, Seoul, South Korea

[17] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

[18] Mayo Clin, Dept Pharm, Rochester, MN USA

[19] Asahi Gen Hosp, Dept Psychiat, Chiba, Japan

[20] Astrakhan State Med Univ, Dept Clin Pharmacol, Astrakhan, Russia

[21] Los Andes Univ, Med Sch, Dept Physiol, Merida, Venezuela

[22] Anahuac Univ, Med Sch, Queretaro, Mexico

[23] Neuroorigen, Queretaro, Mexico

[24] Post Grad Inst Med Educ & Res, Dept Psychiat, Chandigarh, India

[25] Capital & Coast Dist Hlth Board, Te Korowai Whariki Cent Reg Forens Serv, Wellington, New Zealand

[26] Univ Otago, Dept Psychol Med, Wellington, New Zealand

[27] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia

[28] Univ Montana, Dept Pharm Practice, Missoula, MT USA

[29] Ctr Studies Assistance & Res Neurosci, Inst Vilaprino, Mendoza, Argentina

[30] Vilardebo Hosp, Adm Serv Salud, Clin Pharmacol Unit, Montevideo, Uruguay

[31] Vilardebo Hosp, Pharm Dept, Adm Serv Salud, Montevideo, Uruguay

[32] Med Univ Gdansk, Dept Psychiat, Gdansk, Poland

[33] Univ Zagreb, Sch Med, Zagreb, Croatia

[34] Univ Hosp Ctr Zagreb, Dept Psychiat & Psychol Med, Zagreb, Croatia

[35] Hacettepe Univ, Fac Med, Dept Psychiat, Ankara, Turkiye

[36] Univ Kragujevac, Fac Med Sci, Dept Psychiat, Kragujevac, Serbia

[37] Natl Inst Mental Hlth Neurol & Neurosurg, Budapest, Hungary

[38] Univ La Laguna, Sch Med, Dept Phys Med & Pharmacol, San Cristobal la Laguna, Canary Islands, Spain

[39] Hosp Univ Canarias, Tenerife, Spain

[40] Univ La Laguna, Dept Internal Med Dermatol & Psychiat, San Cristobal la Laguna, Canary Islands, Spain

[41] Univ La Laguna, Inst Univ Neurociencia IUNE, San Cristobal la Laguna, Canary Islands, Spain

[42] Eastern State Hosp, Mental Hlth Res Ctr, 1350 Bull Lea Rd, Lexington, KY 40511 USA

来源：

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY | 2023年 / 43卷 / 03期

关键词：

clozapine; adverse effects; administration and dosage; metabolism; therapeutic use; toxicity; COVID-19; drug labeling; infection; inflammation; mortality; drug effects; pneumonia; schizophrenia; sex; smoking; MYOCARDITIS; MORTALITY; RISK;

D O I：

10.1097/JCP.0000000000001678

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Purpose/BackgroundA 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.MethodsHere, 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/ResultsStudies 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/ConclusionsThe 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.

引用

页码：239 / 245

页数：7

共 45 条

[1] A Covid-19 outbreak in a Spanish long-term psychiatric hospital led to infections in 6 clozapine patients: elevations in their plasma clozapine levels [J].