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Fentanyl pills are shown in an undated police handout photo. The opioid's risks are already well known, but a new study suggests narcotic painkillers are almost more likely to cause deaths not related to overdose.The Canadian Press

People who take long-acting opioids for chronic pain are much more likely to die than those taking other medications, according to a study published Tuesday, providing more evidence that the powerful narcotics should be used only as a last resort for ongoing pain.

It is well known that opioids such as oxycodone, morphine and fentanyl have risks. They can suppress the respiratory system, leading to accidental overdose, and they are also addictive.

But in this new study, researchers tried to determine whether those narcotic painkillers are also more likely to cause deaths not related to overdoses. They found that more than two-thirds of the deaths among those taking opioids were not caused by unintentional overdoses. About half were caused by cardiovascular problems.

"This suggests, as we thought, that the existing approaches have underestimated the harms of long-acting opioids," said Wayne Ray, lead author of the study and a professor of health policy at Vanderbilt University Medical Center in Nashville. "I think these data would add even more urgency to reducing the use of opioids."

To do the study, which was published in the Journal of the American Medical Association, researchers studied data from thousands of patients in Tennessee who were either prescribed an opioid, an anticonvulsant used to treat chronic pain, or low-dose cyclic antidepressants, which can also be prescribed for pain. The researchers wanted to make sure that they were counting only people who died as a result of the medication, so they excluded people 75 and older, people with cancer or other life-threatening illnesses, those in end-of-life care and long-term-care residents. They also excluded people with a history of drug abuse.

Most people in the study were diagnosed with back pain, other musculoskeletal pain and abdominal pain.

After looking at the data, the researchers discovered that in the opioid group, there were 167 deaths per 10,000 person years (a measurement based on the number of people in the study and the total number of years of follow-up). In the control group, there were about 108 deaths per 10,000 person years.

The authors said the opioids may have caused or exacerbated breathing problems during sleep such as sleep apnea. Those breathing disruptions are linked to heart problems, which could explain why opioids are linked to a heightened risk of cardiovascular-related death.

The researchers note that, in some cases, opioids might be the right drug to use to treat pain. But over all they are being prescribed too liberally and exposing too many to risk, Ray said. "What one can do is to use opioids as a last resort, basically," he said. "The simple idea is to try other things first."

Some proponents of using opioids to treat long-term pain suggest that the drugs are safe if used cautiously and that the real problem are addicts who purposefully misuse the drugs.

This new research shows that isn't the case, said David Juurlink, senior scientist at Toronto's Institute for Clinical Evaluative Sciences and expert on the risks of opioids. "What we've got here is yet another study that shows the harm associated with long-term opioid therapy. We don't have a single study documenting this is a beneficial thing to do," he said. "I think it does give us reason to rethink how liberally we use these drugs."

Canada is the world's second-largest per capita consumer of opioids next to the United States. Many provinces have instituted drug-monitoring programs to crack down on people who fill prescriptions at multiple pharmacies, but researchers such as Juurlink say much more needs to be done.

Earlier this year, the College of Family Physicians of Canada rejected a call by the Federation of Medical Regulatory Authorities of Canada to make a course on safe opioid prescribing mandatory for family doctors. Earlier this month, the College of Physicians and Surgeons of British Columbia adopted a mandatory opioid-prescribing standard that requires physicians to carefully assess a patient's potential risk factors, review his or her other medications and start him or her on low doses. At the same time, the College of Physicians and Surgeons of Nova Scotia endorsed new guidelines from the U.S. Centers for Disease Control and Prevention that recommend against prescribing opioids for long-term chronic pain because of the risks.

Editor's note: An earlier version of this article incorrectly stated that the College of Family Physicians of British Columbia has adopted a mandatory opioid-prescribing standard. In fact, the measure has been put in place by the College of Physicians and Surgeons of British Columbia. This version has been corrected.

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