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

Carlos De Las Cuevas, Emilio J. Sanz, Alejandro G. Villasante-Tezanos, Jose de Leon

Research output: Contribution to journalReview articlepeer-review


Introduction: Antipsychotics (APs), during treatment or overdose, may be associated with respiratory aspiration. Areas covered: A 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 Opinion: The 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.

Original languageEnglish
Pages (from-to)57-74
Number of pages18
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number2
StatePublished - 2023

Bibliographical note

Funding Information:
This paper was not funded. The authors are indebted to the national centers which make up the World Health Organization (WHO) Program for International Drug Monitoring and contribute reports to VigiBase. The information comes from a variety of sources, and the probability that the suspected adverse effect is drug-related is not the same in all cases. However, the opinions and conclusions of this study are not necessarily those of the various centers nor of the WHO. The authors acknowledge Lorraine Maw, M.A., from the University of Kentucky Mental Health Research Center at Eastern State Hospital, who helped in editing the article.

Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.


  • Airway obstruction
  • antipsychotic agents/adverse effects
  • deglutition disorders
  • dementia
  • drug overdose
  • intellectual disability
  • polypharmacy
  • respiratory aspiration
  • schizophrenia

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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