Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis

Clin J Am Soc Nephrol. 2020 Dec 31;16(1):88-97. doi: 10.2215/CJN.10070620. Epub 2020 Dec 18.


Background and objectives: Zolpidem, a nonbenzodiazepine hypnotic, and trazodone, a sedating antidepressant, are the most common medications used to treat insomnia in the United States. Both drugs have side effect profiles (e.g., drowsiness, dizziness, and cognitive and motor impairment) that can heighten the risk of falls and fractures. Despite widespread zolpidem and trazodone use, little is known about the comparative safety of these medications in patients receiving hemodialysis, a vulnerable population with an exceedingly high fracture rate.

Design, setting, participants, & measurements: Using data from the United States Renal Data System registry (2013-2016), we conducted a retrospective cohort study to investigate the association between the initiation of zolpidem versus trazodone therapy and the 30-day risk of hospitalized fall-related fractures among Medicare-enrolled patients receiving maintenance hemodialysis. We used an active comparator new-user design and estimated 30-day inverse probability of treatment-weighted hazard ratios and risk differences. We treated death as a competing event.

Results: A total of 31,055 patients were included: 18,941 zolpidem initiators (61%) and 12,114 trazodone initiators (39%). During the 30-day follow-up period, 101 fall-related fractures occurred. Zolpidem versus trazodone initiation was associated with a higher risk of hospitalized fall-related fracture (weighted hazard ratio, 1.71; 95% confidence interval, 1.11 to 2.63; weighted risk difference, 0.17%; 95% confidence interval, 0.07% to 0.29%). This association was more pronounced among individuals prescribed higher zolpidem doses (hazard ratio, 1.85; 95% confidence interval, 1.10 to 3.01; and risk difference, 0.20%; 95% confidence interval, 0.04% to 0.38% for higher-dose zolpidem versus trazodone; and hazard ratio, 1.60; 95% confidence interval, 1.01 to 2.55 and risk difference, 0.14%; 95% confidence interval, 0.03% to 0.27% for lower-dose zolpidem versus trazodone). Sensitivity analyses using longer follow-up durations yielded similar results.

Conclusions: Among individuals receiving maintenance hemodialysis, zolpidem initiators had a higher risk of hospitalized fall-related fracture compared with trazodone initiators.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_12_18_CJN10070620_final.mp3.

Keywords: fall; fracture; hemodialysis; insomnia; trazodone; zolpidem.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Accidental Falls / statistics & numerical data
  • Aged
  • Cognitive Dysfunction / chemically induced
  • Dizziness / chemically induced
  • Drug Prescriptions / statistics & numerical data
  • Female
  • Fractures, Bone / epidemiology*
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Medicare / statistics & numerical data
  • Middle Aged
  • Registries
  • Renal Dialysis
  • Renal Insufficiency, Chronic / therapy*
  • Retrospective Studies
  • Sleep Aids, Pharmaceutical / administration & dosage
  • Sleep Aids, Pharmaceutical / adverse effects*
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Trazodone / adverse effects*
  • United States / epidemiology
  • Zolpidem / administration & dosage
  • Zolpidem / adverse effects*


  • Sleep Aids, Pharmaceutical
  • Zolpidem
  • Trazodone