Respiratory aspiration during treatment with clozapine and other antipsychotics: a literature search and a pharmacovigilance study in vigibase

IntroductionAntipsychotics (APs), during treatment or overdose, may be associated with respiratory aspiration.Areas coveredA PubMed search on 30 September 2022, provided 3 cases of respiratory aspiration during clozapine therapy and 1 case during an AP overdose. VigiBase records of respiratory aspiration associated with APs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC).Expert OpinionThe ICs (and IC025) were 2.1 (and 2.0) for APs, 3.2 (and 3.0) for clozapine, 2.6 (and 2.4) for quetiapine, and 2.5 (and 2.2) for olanzapine. Cases of respiratory aspiration associated with APs included: 137 overdose/suicide cases (64 fatal) and 609 cases during treatment (385 fatal) including 333 taking clozapine (238 fatal). In logistic regression models of fatal outcomes, the odds ratios, OR, and (95% confidence intervals, CI) of significant independent variables were: a) 2.3-2.6 for clozapine in 3 samples of AP treatment of varying size, b) 1.9 (CI 1.0 to 3.5) for geriatric age in 284 patients on clozapine treatment, and c) 1.8 (CI 1.1-3.2) for antidepressant co-medication in 276 patients on non-clozapine APs. Multiple AP pharmacological mechanisms may explain respiratory aspiration.

Automated summary

Respiratory aspiration may be associated with antipsychotic (AP) treatment or overdose. Cases of respiratory aspiration were reported during clozapine therapy and AP overdose. The information components (ICs) for APs, clozapine, quetiapine, and olanzapine were relatively high. Respiratory aspiration cases associated with APs included overdose/suicide cases and cases during treatment, with a high fatality rate among patients taking clozapine. Multiple mechanisms of action of APs may contribute to respiratory aspiration.