The prevalence of agranulocytosis and related death in clozapine-treated patients: a comprehensive meta-analysis of observational studies

Psychol Med. 2020 Mar;50(4):583-594. doi: 10.1017/S0033291719000369. Epub 2019 Mar 12.

Abstract

Background: Clozapine treatment increases the risk of agranulocytosis, but findings on the epidemiology of agranulocytosis have been inconsistent. This meta-analysis examined the prevalence of agranulocytosis and related death in clozapine-treated patients.

Methods: A literature search in the international (PubMed, PsycINFO, and EMBASE) and Chinese (WanFang, Chinese National Knowledge Infrastructure, and Sinomed) databases was conducted. Prevalence estimates of agranulocytosis and related death in clozapine-treated patients were synthesized with the Comprehensive Meta-Analysis program using the random-effects model.

Results: Thirty-six studies with 260 948 clozapine-treated patients published between 1984 and 2018 were included in the meta-analysis. The overall prevalence of agranulocytosis and death caused by agranulocytosis were 0.4% (95% CI 0.3-0.6%) and 0.05% (95% CI 0.03-0.09%), respectively. The prevalence of agranulocytosis was moderated by sample size, study quality, year of publication, and that of data collection.

Conclusions: The prevalence of clozapine-associated agranulocytosis is low. Agranulocytosis-related death appears rare.

Keywords: Agranulocytosis; clozapine; meta-analysis; prevalence.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agranulocytosis / chemically induced*
  • Agranulocytosis / epidemiology*
  • Agranulocytosis / mortality
  • Antipsychotic Agents / adverse effects*
  • Cause of Death
  • Clozapine / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / mortality
  • Humans
  • Observational Studies as Topic*
  • Prevalence

Substances

  • Antipsychotic Agents
  • Clozapine