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

Fatal outcomes associated with clozapine adverse drug reactions (ADRs) were studied for over/underrepresentation in geriatric patients.

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.

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.

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).

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.