Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis

Aust N Z J Psychiatry. 2016 Jun;50(6):520-33. doi: 10.1177/0004867415616695. Epub 2015 Nov 20.


Background: Use of hypnotics or anxiolytic drugs is common and various studies have reported increased mortality with hypnotics or anxiolytic use.

Objective: To consolidate the evidence on mortality risk associated with hypnotics or anxiolytic use

Methods: Major databases were searched through April 2014 for studies reporting mortality risk associated with hypnotics or anxiolytics use. A pooled hazard ratio with 95% confidence interval was estimated using random-effects model.

Results: After screening 2188 articles, 25 studies (24 cohort, 1 case-control) enrolling 2,350,093 patients with 59% females (age 18-102 years) were included in the meta-analysis. Hypnotics or anxiolytic users had 43% higher risk of mortality than non-users (hazard ratio, 1.43; 95% confidence interval, [1.12, 1.84]). Eight studies reported risk estimates for each gender category and pooled results from these studies showed increased risk of mortality among men (hazard ratio = 1.60, 95% confidence interval = [1.29,1.99]) and women (hazard ratio = 1.68, 95% confidence interval = [1.38, 2.04]). Pooled results from 10 studies showed higher mortality among benzodiazepine users compared to non-users (hazard ratio = 1.60, 95% confidence interval = [1.03, 2.49]), while pooled results from five studies showed an increased risk of mortality with Z-drugs use although the effect could not reach statistical significance (hazard ratio = 1.73, 95% confidence interval = [0.95, 3.16]). Significant heterogeneity was observed in the analyses and the quality of included studies was good.

Conclusion: This meta-analysis suggests that hypnotics or anxiolytics drugs use is associated with increased mortality and hence should be used with caution. Future studies focused on underlying mechanism of increased mortality with hypnotics or anxiolytics use are required.

Keywords: Hypnotic; Z-drugs; anxiolytic; meta-analysis; mortality; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anti-Anxiety Agents / adverse effects*
  • Benzodiazepines / adverse effects
  • Drug-Related Side Effects and Adverse Reactions / mortality*
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Male


  • Anti-Anxiety Agents
  • Hypnotics and Sedatives
  • Benzodiazepines