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New study establishes risk of death during chronic opioid therapy, showing men at much higher risk than women


Among people receiving chronic opioid therapy, men are more likely than women both to escalate to high doses and to die from opioid-related causes, says a new study from the Institute for Clinical Evaluative Sciences (ICES).

The study, published today in the journal PLOS ONE, examined the records of 285,520 individuals in Ontario receiving opioid treatment over a 13-year period. It is the first large-scale study to confidently assess the risk of overdose death during treatment with chronic opioid therapy.

“Men were twice as likely as women to escalate to high-dose therapy and twice as likely to die from opioid-related causes,” says the study’s senior author and ICES senior scientist Dr. David Juurlink, who is also the head of the Division of Clinical Pharmacology and Toxicology at the University of Toronto. “But even more striking were the overall rates of escalation in both sexes to high-dose therapy and opioid-related death in patients on chronic opioid therapy. Both of these were far higher than we expected, and will likely come as a surprise to many physicians and patients.”

The study found that:

  • Among patients receiving chronic opioid therapy (longer than 3 months), roughly 1 of every 45 men and 1 of every 70 women escalated to high dose therapy (greater than 200 mg morphine or equivalent per day).
  • Opioid-related death occurred in 1 of every 350 men and 1 of every 850 women receiving chronic opioid therapy.
  • Relative to women, men were almost 50 per cent more likely to escalate to high-dose opioids and twice as likely to die from opioid-related causes.
  • Patients who escalated to high dose opioid therapy were nearly 24 times as likely to die as those who did not escalate.
  • More than 1 of every 10 patients prescribed opioids for the first time became chronic users.

Sales of opioids have quadrupled in the last decade, and more than 238 million opioid prescriptions were issued in the United States in 2011 alone, making them the third most widely prescribed drug class. Opioid deaths now represent more than 40 per cent of all mortality from poisoning in North America today, outnumbering deaths from alcoholic liver disease and HIV.

Despite their very widespread use, the researchers say there is little evidence supporting the safety and effectiveness of long-term opioid therapy for chronic pain, especially compared to other analgesics.

“These findings underscore the importance of thinking twice before embarking on chronic opioid therapy, and particularly high-dose therapy.” says Juurlink. “Physicians who opt to prescribe chronic opioid therapy should appreciate these risks, and should ensure their patients understand them too.”

“Sex differences in dose escalation and overdose death during chronic opioid therapy: a population-based cohort study,” was published today in the journal PLOS ONE.

Author block: Eric Kaplovitch, Tara Gomes, Ximena Camacho, Irfan A Dhalla, Muhammad M Mamdani, David Juurlink.

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario


  • Kathleen Sandusky
  • Media Advisor, ICES
  • [email protected]
  • (o) 416-480-4780 or (c) 416-434-7763

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