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

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.