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Fatal outcomes associated with clozapine adverse drug reactions (ADRs) were studied for over/underrepresentation in middle-aged (45-64 years) versus young adult patients (18-44 years). These fatal outcomes were obtained from the worldwide pharmacovigilance database (VigiBase) from inception to January 15, 2023, including 7874 cases of middle-aged adults versus 4380 young adult controls. Fatal outcomes of clozapine ADRs were ranked by frequency; over/underrepresentation was determined by comparison with controls using univariate odds ratios (OR), their 95 % confidence intervals (CIs) and adjusted ORs after adjusting for major confounders. Overrepresentation (12.5 % vs. 5.6 % with an adjusted OR = 2.41; CI: 2.08-2.78) occurred in respiratory complications likely associated with swallowing impairment. It was the most frequent specific fatal outcome in middle-aged patients and accounted for 19 % (983/5237) of fatal outcomes with specific labels. Other overrepresented fatal outcomes were those associated with leukocytosis, 7.4 % vs. 3.7 % (adjusted OR = 2.00, CI: 1.67-2.40); all neoplasms, 6.4 % vs. 1.2 % (adjusted OR = 5.57, CI: 4.19-7.40); and myocardial infarction 6.9 % vs. 4.9 % (adjusted OR=1.50, CI: 1.27-1.77). Underrepresented variables were completed suicide, 2.7 % vs. 8.5 % (adjusted OR = 0.30, CI: 0.25-0.36); pulmonary embolism, 2.1 % vs. 5.0 % (adjusted OR: 0.38, CI: 0.31-0.47); and myocarditis, 0.5 % vs. 1.1 % (adjusted OR = 0.57, CI: 0.38-0.87). These underrepresentations may indicate that fatal outcomes associated with pneumonia or myocardial infarction could be underrepresented in young adults. Future studies need to further explore how early stages of aging from young to middle age influence fatal outcomes in clozapine-treated patients and their association with clozapine versus treatment-resistant schizophrenia.
Cuevas et al. (Thu,) studied this question.