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Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study

BMJ 2015; 350 doi: (Published 10 June 2015) Cite this as: BMJ 2015;350:h2698
  1. Tae Woo Park, assistant professor1,
  2. Richard Saitz, chair2,
  3. Dara Ganoczy, research health science specialist3,
  4. Mark A Ilgen, associate professor34,
  5. Amy S B Bohnert, assistant professor34
  1. 1Departments of Medicine and Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, 111 Plain Street, Providence, RI 02903, United States
  2. 2Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Ave, Boston, MA 02118, USA
  3. 3Department of Veterans Affairs, Health Services Research and Development (HSR&D), 2215 Fuller Road, Ann Arbor, MI 48105, USA
  4. 4Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
  1. Correspondence to: T W Park, tpark1{at}
  • Accepted 15 April 2015


Objective To study the association between benzodiazepine prescribing patterns including dose, type, and dosing schedule and the risk of death from drug overdose among US veterans receiving opioid analgesics.

Design Case-cohort study.

Setting Veterans Health Administration (VHA), 2004-09.

Participants US veterans, primarily male, who received opioid analgesics in 2004-09. All veterans who died from a drug overdose (n=2400) while receiving opioid analgesics and a random sample of veterans (n=420 386) who received VHA medical services and opioid analgesics.

Main outcome measure Death from drug overdose, defined as any intentional, unintentional, or indeterminate death from poisoning caused by any drug, determined by information on cause of death from the National Death Index.

Results During the study period 27% (n=112 069) of veterans who received opioid analgesics also received benzodiazepines. About half of the deaths from drug overdose (n=1185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of death from drug overdose increased with history of benzodiazepine prescription: adjusted hazard ratios were 2.33 (95% confidence interval 2.05 to 2.64) for former prescriptions versus no prescription and 3.86 (3.49 to 4.26) for current prescriptions versus no prescription. Risk of death from drug overdose increased as daily benzodiazepine dose increased. Compared with clonazepam, temazepam was associated with a decreased risk of death from drug overdose (0.63, 0.48 to 0.82). Benzodiazepine dosing schedule was not associated with risk of death from drug overdose.

Conclusions Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose-response fashion.


  • Contributors: All authors have fulfilled authorship criteria per ICMJE guidelines and have approved the manuscript and this submission. TP, RS, and ASBB were involved in the conception or design of the work. TP, DG, and ASBB were involved in acquisition and analysis of data. All authors were involved in interpretation of data. TP and ASBB drafted the manuscript and all authors revised the work critically for important intellectual content. All coauthors approve this version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. TP is guarantor.

  • Funding: This work was supported by funding from a Veteran Affairs Health Services Research and Development Service Career Development Award (CDA‐09‐204; ASBB.) and by the National Institutes of Health (R03 AG042899). The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript of the decision to submit.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: financial support as specified above; RS has received consultant and annual travel fees from The BMJ as editor of the journal Evidence Based Medicine; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study procedures received approval from the Ann Arbor VA human studies committee, which waived the requirement for informed consent.

  • Transparency declaration: All authors affirm that this 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 from the study as planned (and, if relevant, registered) have been explained.

  • Data sharing: Veterans Health Administration (VHA) treatment data are maintained and available for the VHA community through VA Informatics and Computing Infrastructure (

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