Analysis of anticholinergic adverse effects using two large databases: The US Food and Drug Administration Adverse Event Reporting System database and the Japanese Adverse Drug Event Report database

PLoS One. 2021 Dec 2;16(12):e0260980. doi: 10.1371/journal.pone.0260980. eCollection 2021.

Abstract

Introduction: Anticholinergic adverse effects (AEs) are a problem for elderly people. This study aimed to answer the following questions. First, is an analysis of anticholinergic AEs using spontaneous adverse drug event databases possible? Second, what is the main drug suspected of inducing anticholinergic AEs in the databases? Third, do database differences yield different results?

Methods: We used two databases: the US Food and Drug Administration Adverse Event Reporting System database (FAERS) and the Japanese Adverse Drug Event Report database (JADER) recorded from 2004 to 2020. We defined three types of anticholinergic AEs: central nervous system (CNS) AEs, peripheral nervous system (PNS) AEs, and a combination of these AEs. We counted the number of cases and evaluated the ratio of drug-anticholinergic AE pairs between FAERS and JADER. We computed reporting odds ratios (RORs) and assessed the drugs using Beers Criteria®.

Results: Constipation was the most reported AE in FAERS. The ratio of drug-anticholinergic AE pairs was statistically significantly larger in FAERS than JADER. Overactive bladder agents were suspected drugs common to both databases. Other drugs differed between the two databases. CNS AEs were associated with antidementia drugs in FAERS and opioids in JADER. In the assessment using Beers Criteria®, signals were detected for almost all drugs. Between the two databases, a significantly higher positive correlation was observed for PNS AEs (correlation coefficient 0.85, P = 0.0001). The ROR was significantly greater in JADER.

Conclusions: There are many methods to investigate AEs. This study shows that the analysis of anticholinergic AEs using spontaneous adverse drug event databases is possible. From this analysis, various suspected drugs were detected. In particular, FAERS had many cases. The differences in the results between the two databases may reflect differences in the reporting countries. Further study of the relationship between drugs and CNS AEs should be conducted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / epidemiology
  • Central Nervous System Diseases / pathology
  • Cholinergic Antagonists / adverse effects*
  • Databases, Factual / statistics & numerical data*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Humans
  • Japan / epidemiology
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / epidemiology
  • Peripheral Nervous System Diseases / pathology
  • Software
  • United States / epidemiology

Substances

  • Cholinergic Antagonists

Grants and funding

This work was supported by JSPS (The Japan Society for the Promotion of Science) KAKENHI for Grant-in-Aid for Early-Career Scientists Grant Number 19K16424 to J.N. https://www.jsps.go.jp/english/index.html The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.