Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK

• Published in: Schizophrenia research Vol. 268; pp. 175 - 188
• Main Authors: De las Cuevas, Carlos, Sanz, Emilio J., Gross, Jason A., Correll, Christoph U., Verdoux, Hélène, Lally, John, de Filippis, Renato, Schulte, Peter F.J., Molden, Espen, Arrojo-Romero, Manuel, Bostrom, Adrian D., Schoretsanitis, Georgios, Fernandez-Egea, Emilio, de Leon, Jose
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2024; Elsevier
• Subjects: Clozapine/administration and dosage; Clozapine/adverse effects; Clozapine/therapeutic use; Drug labeling; Europe; Life Sciences; Medicin och hälsovetenskap; Santé publique et épidémiologie; Schizophrenia; Clozapine/administration and dosage; Schizophrenia; Clozapine/therapeutic use; Europe; Clozapine/adverse effects; Drug labeling
• ISSN: 0920-9964; 1573-2509; 1573-2509
• DOI: 10.1016/j.schres.2023.11.010

Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label “death” was the top cause in the world (46 %) and in the UK (33 %). “Pneumonia” was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1–10 % of the UK clozapine fatal outcome number. Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases. [Display omitted]