Search   |  Advanced

Research Summary

Opioid-Related Death in Patients with Nonmalignant Pain

To assess the association between opioid dose and opioid-related death in patients with nonmalignant pain, researchers used administrative and pharmacy records to conduct a case-control study of 607,156 patients aged 15 to 64 years who received a prescription opioid between 1997 and 2006. Cases were opioid-related deaths as determined by a coroner. Controls were matched to cases based on age, gender, receipt of opioids during the year of the index date (date of case’s death), comorbidity, and disease-risk index results. For cases and controls, the average daily opioid dose at the index date was calculated and converted into morphine equivalents in milligrams (mg). Four hundred ninety-eight opioid-related deaths and 1714 patients met criteria for inclusion as cases and controls, respectively.

  • The average age of cases at the time of death was 43 years. The majority of deaths were accidental.
  • Compared with controls, cases were more likely to have received psychotropic drugs, methadone, benzodiazepines, and antidepressants; to have used multiple physicians or pharmacies for opioid prescriptions; and to have current or past alcohol dependence.
  • In analyses controlling for confounders, when compared with a reference of <20 mg morphine equivalents, increasing daily opioid dose was associated with greater risk of opioid-related death:
    • 20–49 mg (odds ratio [OR], 1.3).
    • 50–99 mg (OR, 1.9).
    • 100–199 mg (OR, 2.0).
    • >200 mg (OR, 2.9).


This study showed increasing risk of opioid-related death as the daily dose increased, including a 3-fold increase in risk at doses (>200 mg per day) that exceed recommendations for nonmalignant pain. Although the absolute risk of opioid-related death is low, the results argue for clinical caution when prescribing opioids for nonmalignant pain, for identifying risks such as alcohol dependence or use of other psychoactive medications, and for assuring appropriate opioid dosage and mitigation of use in patients taking other prescribed medications. Kevin L. Kraemer, MD, MSc


Gomes T, Mamdani MM, Dhalla IA, et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171(7):686–691.