| アブストラクト | BACKGROUND: Pharmacovigilance findings and box warnings in the clozapine package inserts have marked the history of clozapine. OBJECTIVE: This is the largest review of clozapine adverse drug reactions (ADRs) and their associated fatal outcomes. Reports to the World Health Organization's global pharmacovigilance database, VigiBase, were analyzed, extending from clozapine's introduction to December 31, 2022. METHODS: The analysis focused on the top four reporting countries: United States (US), United Kingdom (UK), Canada and Australia (83 % of fatal outcomes worldwide). Attempts were made to control for population and clozapine prescription in each country. RESULTS: Clozapine ADRs worldwide accounted for 191,557 reports, with the highest number (53,505) in "blood and lymphatic system disorder". Of the 22,596 fatal outcomes reported in clozapine patients, 9587 were from the US, 6567 from the UK, 3623 from Canada and 1484 from Australia. The top category worldwide in fatal outcomes was nonspecifically labeled "death" with 46 % (range 22-62 %). "Pneumonia" was second with 30 % (range 17-45 %). Agranulocytosis was numerically only the 35th top clozapine ADR associated with fatal outcomes. On average, 2.3 clozapine ADRs were reported per fatal outcome. Infections were associated with 24.2 % of the UK fatal outcomes (9.4 %-11.9 % in the 3 other countries). CONCLUSIONS: The four countries appeared to report clozapine ADRs in different ways, making comparisons difficult. We estimated higher fatal outcomes in the UK and Canada after controlling for cross-sectional estimations of population and published clozapine use. This last hypothesis is limited by the lack of precise estimation of accumulated clozapine use in each country. |
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| ジャーナル名 | Schizophrenia research |
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| 投稿日 | 2023/6/11 |
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| 投稿者 | De Las Cuevas, Carlos; Sanz, Emilio J; de Leon, Jose |
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| 組織名 | Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine,;University of La Laguna, Canary Islands, Spain; Instituto Universitario de;Neurociencia (IUNE), Universidad de La Laguna, San Cristobal de La Laguna, Spain.;Electronic address: ccuevas@ull.edu.es.;Department of Physical Medicine and Pharmacology, School of Medicine, Universidad;de La Laguna, Canary Islands, Spain; Hospital Universitario de Canarias,;Tenerife, Spain.;Mental Health Research Center at Eastern State Hospital, Lexington, KY, USA;;Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol;Hospital, University of the Basque Country, Vitoria, Spain. Electronic address:;jdeleon@uky.edu. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37301669/ |
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