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Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis

BMJ 2017; 356 doi: (Published 14 March 2017) Cite this as: BMJ 2017;356:j760
  1. Eric C Sun, assistant professor1,
  2. Anjali Dixit, resident physician2,
  3. Keith Humphreys, professor3,
  4. Beth D Darnall, clinical associate professor1,
  5. Laurence C Baker, professor4,
  6. Sean Mackey, Redlich professor1
  1. 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, 300 Pasteur Dr, H3580, Stanford, CA 94305, USA
  2. 2Department of Anesthesiology and Perioperative Care, University of California, San Francisco, 521 Parnassus Ave, San Francisco, CA 94131, USA
  3. 3Center for Innovation to Implementation, VA Palo Alto Health Care System and Department of Psychiatry, Stanford University School of Medicine, Stanford University, 401 N Quarry Road, MC:5717, Stanford, CA 94305, USA
  4. 4Department of Health Research and Policy, Stanford University School of Medicine, Stanford University and National Bureau of Economic Research, 150 Governor’s Lane, HRP Redwood Building, Stanford, CA 94305, USA
  1. Correspondence to: E Sun esun1{at}
  • Accepted 30 January 2017


Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.

Design Retrospective analysis of claims data, 2001-13.

Setting Administrative health claims database.

Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.

Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug.

Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.

Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).

Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.


  • Contributors: All authors contributed to the design and conduct of the study, data collection and management, analysis interpretation of the data; and preparation, review, or approval of the manuscript. ECS is guarantor.

  • Funding: ECS was supported by a mentored research training grant from the Foundation for Anesthesia Education and Research and the Anesthesia Quality Institute. KNH was supported by funding from the Veterans Affairs health services research and development service. The research conducted was independent of any involvement from the sponsors of the study. Study sponsors were not involved in study design, data interpretation, writing, or the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: support provided by grants from the Foundation for Anesthesia Education and Research; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required as patient data were de-identified.

  • Data sharing: No additional data available.

  • Transparency statement: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies are disclosed.

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