Article Text

Original research
Concurrent use of opioids and benzodiazepines/Z-drugs in Alberta, Canada and the risk of hospitalisation and death: a case cross-over study
  1. Vishal Sharma1,
  2. Scot H Simpson2,
  3. Salim Samanani3,
  4. Ed Jess4,
  5. Dean T Eurich1
  1. 1School of Public Health, University of Alberta, Edmonton, Alberta, Canada
  2. 2Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
  3. 3Okaki Health Intelligence, Calgary, Alberta, Canada
  4. 4The College of Physicians & Surgeons of Alberta, Edmonton, Alberta, Canada
  1. Correspondence to Professor Dean T Eurich; deurich{at}


Objectives Coprescribing of benzodiazepines/Z-drugs (BZDs) and opioids is a drug-use pattern of considerable concern due to risk of adverse events. The objective of this study is to estimate the effect of concurrent use of BZDs on the risk of hospitalisations/emergency department (ED) visits and deaths among opioid users.

Design, setting and participants We conducted a population-based case cross-over study during 2016–2018 involving Albertans 18 years of age and over who received opioids. From this group, we identified 1 056 773 people who were hospitalised or visited the ED, and 31 998 who died.

Intervention Concurrent use of opioids and BZDs.

Outcomes We estimated the risk of incident all-cause hospitalisation/ED visits and all-cause mortality associated with concurrent BZD use by applying a matched-pair analyses comparing concurrent use to opioid only use.

Results Concurrent BZD use occurred in 17% of opioid users (179 805/1 056 773). Overall, concurrent use was associated with higher risk of hospitalisation/ED visit (OR 1.13, p<0.001) and all cause death (OR 1.90; p<0.001). The estimated risk of hospitalisation/ED visit was highest in those >65 (OR 1.5; p<0.001), using multiple health providers (OR 1.67; p<0.001) and >365 days of opioid use (OR 1.76; p<0.001). Events due to opioid toxicity were also associated with concurrent use (OR 1.8; p<0.001). Opioid dose-response effects among concurrent patients who died were also noted (OR 3.13; p<0.001).

Interpretation Concurrent use of opioids and BZDs further contributes to the risk of hospitalisation/ED visits and mortality in Alberta, Canada over opioid use alone, with higher opioid doses, older age and increased number of unique health providers carrying higher risks. Regulatory bodies and health providers should reinforce safe drug-use practices and be vigilant about coprescribing.

  • epidemiology
  • public health
  • substance misuse
  • pain management
  • adverse events

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  • Contributors VS, DTE, SHS, SS and EJ were involved in the conception and design of the study. VS, SHS and DTE analysed the data. VS and DTE drafted the article. EJ, SHS and SS revised the article. All authors gave final approval of the version to be published. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. DTE is the guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; SS has received research grants from the College of Physicians and Surgeons of Alberta; no other relationships or activities that could appear to have influenced the submitted work.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the health ethics research board at the University of Alberta (#Pro00083807).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. No data are available.The data used in this study are not available for external analysis. However, administrative health data can be accessed from Alberta Health by following defined research protocols and confidentiality agreements.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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