| アブストラクト | OBJECTIVE: Fatal outcomes associated with clozapine adverse drug reactions (ADRs) were studied for over/underrepresentation in geriatric patients. DESIGN, SETTING, PARTICIPANTS: The worldwide pharmacovigilance database (VigiBase) was studied for fatal outcomes associated with clozapine ADRs from 1974 to January 15, 2023. They included 5,370 geriatric cases (>/=65 years) versus 12,254 nongeriatric adult controls. MEASUREMENTS: Fatal outcomes of clozapine ADRs were ranked by frequency. Over/underrepresentation was determined by comparison with nongeriatric controls using univariate odds ratios (OR), their 95% confidence intervals (CIs) and adjusted ORs after adjusting for major confounders. RESULT: Respiratory complications likely associated with swallowing impairment led to 1,042 fatal outcomes (19% of all geriatric fatal outcomes and 31% of those with specific information) and was the most overrepresented ADR among the geriatric cases (adjusted OR = 2.53; CI, 2.31-2.78). More than 99% of these 1,042 respiratory fatal outcomes were not explained by agranulocytosis. Agranulocytosis led to only 39 fatal outcomes (0.7% of the geriatric fatal outcomes) and was underrepresented in the geriatric cases (adjusted OR = 0.59; CI, 0.41-0.85). Other underrepresented fatal outcomes were acute cardiac fatal outcomes (adjusted OR = 0.62, CI, 0.59-0.69), myocarditis (adjusted OR = 0.08, CI, 0.03-0.25), completed suicide (adjusted OR=0.14, CI 0.09-0.14) and pulmonary embolism (adjusted OR = 0.37, CI, 0.28-0.49). CONCLUSION: As hematological monitoring is used in most countries for clozapine, agranulocytosis is very rarely fatal. According to VigiBase, in order to prevent the largest number of deaths in clozapine-treated patients, psychiatrists need to focus on respiratory complications likely associated with swallowing impairment; this is most evident in geriatric patients. |
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| 投稿者 | de Leon, Jose; Ruan, Can-Jun; Schoretsanitis, Georgios; Verdoux, Helene; Friedman, Joseph; Sanz, Emilio J; De Las Cuevas, Carlos |
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| 組織名 | Mental Health Research Center (JdL), Eastern State Hospital, Lexington, KY;;Biomedical Research Centre in Mental Health Net (CIBERSAM) (JdL), Santiago;Apostol Hospital, University of the Basque Country, Vitoria, Spain. Electronic;address: jdeleon@uky.edu.;The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of;Mental Disorders (CJR), Beijing Anding Hospital, Capital Medical University,;Beijing, China; Advanced Innovation Center for Human Brain Protection (CJR),;Capital Medical University, Beijing, China.;The Department of Psychiatry (GS), Psychotherapy and Psychosomatics, Psychiatric;Hospital, University of Zurich, Zurich, Switzerland; The Zucker Hillside Hospital;(GS), Psychiatry Research, Northwell Health, Glen Oaks, NY; Zucker School of;Medicine at Hofstra/Northwell (GS), Hempstead, NY.;University of Bordeaux (HV), Inserm, Bordeaux Population Health Research Center,;team pharmacoepidemiology, Bordeaux, France.;Movement Disorders Program (JF), Butler Hospital Department of Neurology, Warren;Alpert Medical School of Brown University, Providence, RI.;The Department of Physical Medicine and Pharmacology (EJS), School of Medicine,;Universidad de La Laguna, Canary Islands, Spain; Hospital Universitario de;Canarias (EJS), Tenerife, Spain.;Department of Internal Medicine (CDlC), Dermatology and Psychiatry, School of;Medicine, and Instituto Universitario de Neurociencia (IUNE), University of La;Laguna, Canary Islands, Spain. |
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