Legally Prescribed Opioid Use May Increase Mortality in Chronic Pain Patients

Legally Prescribed Opioid Use May Increase Mortality in Chronic Pain Patients

According to a New Study Published in PAIN®
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Thursday, November 13, 2014 - 1:00pm

CONTENT: Press Release

PHILADELPHIA, November 13, 2014 /3BL Media/ – Associations between opioid-related overdoses and increased prescription of opioids for chronic noncancer pain are well known. But some suggest that overdose occurs predominately in individuals who obtain opioids from nonmedical sources. In a new study published in the November issue of the journal PAIN®, researchers in Denmark found an increased risk of death associated with chronic pain without opioid treatment, as well as an even higher risk among those prescribed opioids for long-term use and a somewhat lower risk associated with short-term use.

“Our study provides the first evidence that directly links legally prescribed opioids to risk of deaths related to short- and long-term opioid use in patients with chronic noncancer pain,” notes lead investigator Ola Ekholm, a senior advisor in the National Institute of Public Health, University of Southern Denmark in Copenhagen.

In the United States and Denmark, about 3% to 5% of the populations are using opioids regularly for treatment of chronic pain. In the U.S. from 1999 to 2010, the number of dispensed opioid prescriptions doubled (120 million to 210 million), and during the same period annual deaths related to opioid overdoses quadrupled from 4,030 to 16,651.

Using data from two Danish Health and Morbidity surveys from 2000 and 2005, combined with information from official Danish health-care statistics and socioeconomic registers, researchers from the University of Southern Denmark and the Rigshospitalet Copenhagen University Hospital in Copenhagen found that the risk of all-cause mortality was 1.72 times higher among long-term opioid users and 1.39 times higher among non-opioid-using chronic pain patients than among individuals without chronic pain. Although the study showed no statistically significant association between long-term opioid use and cardiovascular and cancer mortality, the results indicated that risk of death due to other causes was almost 2.4 times higher among long-term opioid users than among individuals without chronic pain.

Investigators also determined that long-term opioid users had four times higher risk of toxicity/poisoning by drugs, medications, and biological substances than individuals without chronic pain. Non-opioid users with chronic pain also had a higher mortality risk but did not present with higher risk for poisoning by drugs, medications, and biological substances. They did, however, have a slightly higher risk for injury, poisoning, and certain other consequences of external causes when compared with individuals without chronic pain.

In an accompanying commentary, Harald Breivik, MD, DMSc, and Audun Stubhaug, MD, DMSc, from the Department of Pain Management and Research, University of Oslo and Oslo University Hospital, Oslo, Norway, pose a number of important questions about opioid treatment of chronic pain.

Dr. Breivik and Dr. Stubhaug comment that the most robust finding in the Danish study is the higher mortality rate in chronic pain patients not using opioids compared with persons without pain. They note that opioids may aggravate this burden of disease in chronic-pain patients, but it remains to determine whether this higher mortality rate is caused by the opioid treatment or the seriousness of the pain problem. They discuss how the relatively liberal attitude toward prescribing opioids in Denmark contrasts with the more restrictive policies in neighboring Nordic countries and assert that striking a balance poses a major challenge in pain medicine.

The final question they propose is whether the primary culprit is opioids per se or the way in which patients are treated with opioids. They write: “Safe and effective treatment of opioid-sensitive pain is possible but continues to be a double-edged sword that is difficult to handle. It requires deep pharmacological knowledge, experience, resources, considerable patience, and mental energy from a group of helpers who are able to take care of the whole bio-psycho-social conundrum of the chronic pain patient.”


Notes for editors
“Chronic pain, opioid prescriptions, and mortality in Denmark: A population-based cohort study,” by Ola Ekholm, Geana Paula Kurita, Jette Højsted, Knud Juel, and Per Sjøgren (DOI:

“Burden of disease is often aggravated by opioid treatment of chronic pain patients: Etiology and prevention,” by Harald Breivik and Audun Stubhaug (DOI:

Both articles appear in PAIN®, Volume 155/Issue 11 (November 2014), published by Elsevier.

Full text of these articles are available to credentialed journalists upon request. Contact Terry Materese at +1 215 239 3196 or for copies. Journalists wishing to interview the authors of Ekholm et al. should contact Geana Paula Kurita at Dr. Breivik may be contacted at

About PAIN®
PAIN®, the official journal of the International Association for the Study of Pain® (IASP®), publishes 12 issues per year of original research on the nature, mechanisms, and treatment of pain. This peer-reviewed journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest and is cited in Current Contents and MEDLINE. It is ranked #2 out of the 29 journals in the Anesthesiology category, according to the 2013 Journal Citation Reports, published by Thomson Reuters.

About the International Association for The Study of Pain® (Iasp®)
IASP® is the world's largest multidisciplinary organization focused specifically on pain research and treatment. It is the leading professional forum for science, practice, and education in the field of pain, bringing together scientists, clinicians, health-care providers, and policymakers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide. Founded in 1973, IASP has nearly 8,000 members from 133 countries and in 90 chapters.

About Elsevier
Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey — and publishes nearly 2,200 journals, including The Lancet and Cell, and over 25,000 book titles, including a number of iconic reference works.

The company is part of Reed Elsevier Group PLC, a world-leading provider of professional information solutions in the Science, Medical, Legal and Risk and Business sectors, which is jointly owned by Reed Elsevier PLC and Reed Elsevier NV. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Media contact
Terry Materese
+1 215 239 3196
+1 215 327 9934