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Publication Briefs

Study Suggests Veterans Receiving Higher-Dose Opioid Prescriptions for Pain at Increased Risk of Death from Overdose

Between 1999 and 2007, the rate of death from unintentional overdose in the U.S. increased by 124%, largely due to increases in prescription opioid overdoses. This study examined the association of maxiumum prescribed daily opioid dose and dosing schedule (“as needed,” regularly scheduled, or both) with risk of opioid overdose death among Veterans with cancer, chronic pain, acute pain, and substance use disorders. Investigators also adjusted for patient demographics and comorbid conditions. Using both VA and National Death Index data, investigators identified a random sample of Veterans who used VA healthcare in FY04 and FY05 and received opioid therapy for pain (n=154,684), in addition to all Veterans who had died unintentionally from a prescription opioid overdose (n=750). All patients were followed through FY08. Veterans with indications of palliative care or hospice care were excluded.


  • Among Veterans receiving opioid prescriptions for pain, higher opioid doses were associated with increased risk of death from opioid overdose.
  • The frequency of fatal overdose among Veterans treated with opioids was rare – estimated to be 0.04% - and was directly related to the maximum prescribed daily dose of opioid medication. For example, risk of opioid overdose increased when opioid dose was equivalent to 50mg/d or more of morphine.
  • There was no significant increased risk of opioid overdose among Veterans who were treated with both “as-needed” and regularly scheduled opioids – a strategy for treating pain exacerbations – after adjusting for maximum daily dose and patient characteristics.
  • Veterans who died from opioid overdose were significantly more likely to be middle-aged and white, and to have chronic or acute pain, substance use disorders, and other psychiatric disorders, but they were less likely to have cancer.
  • This study highlights the importance of implementing strategies for reducing opioid overdose among patients being treated for pain, for example, ascertaining history of substance abuse, using treatment contracts, and scheduling frequent follow-up visits and toxicological screens for patients at special risk.


  • Investigators were unable to measure actual opioid doses consumed by patients on any given day; also, semi-synthetic opioids, which may have a particularly high risk for overdose, were excluded.
  • Some of the deaths may have been suicides misclassified as unintentional overdoses.
  • The use of medical records likely resulted in the under-detection of medical conditions.

Dr. Bohnert was supported by an HSR&D Career Development Award. Drs. Bohnert and Valenstein are part of HSR&D’s Center for Clinical Management Research, Ann Arbor, MI.

PubMed Logo Bohnert A, Valenstein M, Bair M, et al. Association between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths. JAMA April 6, 2011;305(13):1315-1321.

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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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