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Publication Briefs

Receipt of Opioid Analgesics and Benzodiazepines Associated with Increased Risk of Death Due to Drug Overdose

Drug overdose deaths, particularly involving opioid analgesics are now among the leading causes of injury mortality in the United States. Moreover, 30% of opioid analgesic-related overdose deaths involve benzodiazepines. This case-cohort study sought to describe the relationship between the receipt of concurrent benzodiazepines and opioid analgesics and death due to drug overdose in patients receiving prescription opioids for acute, chronic, and non-terminal cancer pain. Investigators identified Veterans who received VA healthcare and opioid analgesic medications as outpatients between FY2004 and FY2009, including 112,069 Veterans who also received benzodiazepines and 310,717 Veterans who received no benzodiazepines. Using data from the National Death Index, the main outcome was death due to drug overdose, including any intentional, unintentional or indeterminate poisoning death caused by any medication or drug. Investigators also assessed patient demographics, socioeconomics, diagnoses, and medical comorbidity.


  • During the study period, 27% of Veterans who received opioid analgesics also received benzodiazepines. Among those receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death due to drug overdose.
  • About half of the overdose deaths (n=1,185) occurred when Veterans were concurrently prescribed benzodiazepines and opioids.
  • Patients who were prescribed concurrent opioids and benzodiazepines –and then stopped receiving benzodiazepines had higher rates of overdoes than those patients who had only received opioids.
  • Veterans who received benzodiazepines were more likely to be female, middle-aged, white, and to reside in wealthier areas. Veterans who received benzodiazepines were also more likely to have had a recent mental health or substance use disorder-related hospitalization, a diagnosis of a substance use disorder or a number of psychiatric disorders (i.e., PTSD, depression, anxiety).


  • Treatment (including medications) received from non-VA providers was not examined.
  • Daily dose calculations for benzodiazepines and opioid analgesics were based on Veterans taking medications as prescribed.
  • Investigators were unable to ascertain the indications for which benzodiazepines were prescribed.
  • Data used for this study were from 2004 to 2009.


  • These findings provide empirical support for the goal of the VA Opioid Safety Initiative (OSI) to reduce unnecessary co-prescribing of opioids and benzodiazepines, for which there had been limited evidence prior to this study.

This study was partly funded by HSR&D, and Dr. Bohnert was supported by an HSR&D Career Development Award. Drs. Ilgen and Bohnert are part of HSR&D's Center for Clinical Management Research in Ann Arbor, MI.

PubMed Logo Park T, Saitz R, Ganoczy D, Ilgen M, and Bohnert A. Benzodiazepine Prescribing Patterns and Drug Overdose Deaths among U.S. Veterans Receiving Opioid Analgesics: Case Cohort Study. The British Medical Journal. June 10, 2015;350:h2698.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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