The association between benzodiazepines and influenza-like illness-related pneumonia and mortality: a survival analysis using UK Primary Care data

Pharmacoepidemiol Drug Saf. 2016 Nov;25(11):1263-1273. doi: 10.1002/pds.4028. Epub 2016 May 23.

Abstract

Purpose: Bacterial superinfections, including pneumonia, are frequent complications of influenza-like illness (ILI). Clinical and laboratory evidence suggests that benzodiazepines and Z-drugs may influence susceptibility to infections and mortality. We investigated whether benzodiazepines and zopiclone modify the occurrence of ILI-related pneumonia and mortality.

Methods: We obtained data on 804 051 ILI patients from a comprehensive primary care database, the Clinical Practice Research Datalink. The follow-up period started from the diagnosis of ILI for 30 days. Pneumonia and deaths occurring within the 30-day follow-up period were considered as potentially 'ILI related'. Exposure to benzodiazepines and zopiclone was determined in the period preceding a diagnosis of ILI with current use defined as a prescription for benzodiazepines in the month prior to ILI diagnosis. Cox regression was used for the analyses. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) are presented.

Results: Influenza-like illness-related pneumonia and mortality were noted in 1117 and 707 ILI patients, respectively. Current exposure to benzodiazepines was associated with increased occurrence of both ILI-related pneumonia and mortality (ILI-related pneumonia adjusted HR 4.24, 95%CI [2.27, 7.95]; ILI-related mortality adjusted HR 20.69, 95%CI [15.54, 27.54]). A similar increase in ILI-related mortality but not pneumonia was observed with current zopiclone use (ILI-related mortality adjusted HR 10.86, 95%CI [6.93, 17.02]; ILI-related pneumonia adjusted HR 1.97, 95%CI [0.63, 6.12]).

Conclusion: Benzodiazepines may increase the likelihood of pneumonia and mortality related to ILI. A cautionary approach to prescribing benzodiazepine is suggested in people known to be at increased risk of pneumonia or mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: benzodiazepines; influenza-like illness; mortality; pharmacoepidemiology; pneumonia; zopiclone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Azabicyclo Compounds / administration & dosage
  • Azabicyclo Compounds / adverse effects
  • Bacterial Infections / etiology*
  • Bacterial Infections / mortality
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Cohort Studies
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects
  • Influenza, Human / complications
  • Influenza, Human / mortality
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Pneumonia / etiology*
  • Pneumonia / mortality
  • Primary Health Care
  • Proportional Hazards Models
  • Retrospective Studies
  • Superinfection / etiology*
  • Superinfection / mortality
  • Survival Analysis
  • United Kingdom
  • Young Adult

Substances

  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • zopiclone
  • Benzodiazepines