A Comparative Analysis of Fatal Outcomes in 5,370 Geriatric Versus 12,254 Nongeriatric Adult Patients: A Clozapine Study in VigiBase

  1. de Leon, Jose
  2. Ruan, Can-Jun
  3. Schoretsanitis, Georgios
  4. Verdoux, Hélène
  5. Friedman, Joseph
  6. Sanz, Emilio J. 1
  7. De las Cuevas, Carlos 1
  1. 1 Universidad de La Laguna
    info
    Universidad de La Laguna

    San Cristobal de La Laguna, España

    ROR https://ror.org/01r9z8p25

    Geographic location of the organization Universidad de La Laguna
Journal:
The American Journal of Geriatric Psychiatry

ISSN: 1064-7481

Year of publication: 2026

Volume: 34

Issue: 4

Pages: 591-601

Type: Article

DOI: 10.1016/J.JAGP.2025.08.010 GOOGLE SCHOLAR lock_openOpen access editor

More publications in: The American Journal of Geriatric Psychiatry

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Abstract

ObjectiveFatal outcomes associated with clozapine adverse drug reactions (ADRs) were studied for over/underrepresentation in geriatric patients.Design, Setting, ParticipantsThe 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.MeasurementsFatal 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.ResultRespiratory 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).ConclusionAs 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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