August 23, 2015 - 7:00 AM
TORONTO - Men prescribed opioids like oxycodone for chronic non-cancer pain are twice as likely as women to escalate to a high dose and die as a result of taking the powerful drugs, a study suggests.
The research by the Institute for Clinical Evaluative Sciences (ICES) found that one in 45 men amplified their dosage over time to more than 200 milligrams of morphine or its equivalent, compared with one in 70 women taking the drugs.
Patients whose opioid use had snowballed were almost 24 times as likely to die as those who did not ramp up the amount of their daily medication, concluded the study, published Thursday in the journal PLOS ONE.
"The absolute risks here are just staggering," said senior author Dr. David Juurlink, head of clinical pharmacology and toxicology at the University of Toronto.
"This is really the first large-scale study to give us an idea of how likely it is that patients who are receiving chronic opioid therapy will die from their treatment," said Juurlink. "And as somebody who has been quite critical of these drugs over the years, the findings surprise even me."
The 1997-2010 study, which examined health records for more than 285,500 Ontarians aged 15 to 64, found that more than one in every 10 patients prescribed the drugs for the first time became chronic users.
As well, one in every 350 men and one in every 850 women died as a result of taking an opioid long-term.
"One in 350 doesn't sound especially high, but remember there are tens of millions of patients on these drugs, and we're talking about death," said Juurlink. "So from a public health perspective, that's a very big deal."
Opioids like oxycodone, morphine and hydromorphone are prescribed short-term to patients with acute pain from injury, for instance, and have been a significant boon to those suffering from severe pain due to cancer.
Doctors also often prescribe them for chronic conditions such as low back pain, osteoarthritis, pelvic pain and fibromyalgia.
"These are all conditions where there isn't good evidence for the use of opioids long-term," said Juurlink. "And, in fact, in some of those conditions it's actively discouraged.
"And yet it happens, and it happens in part because doctors are desperate to help patients and patients with pain are desperate themselves, and we don't have a lot of drugs at our disposal."
While women are more likely to be prescribed opioids, men are more likely to be given a more potent agent, research has shown.
"I think doctors are probably more comfortable giving stronger drugs to men ... So when you are on stronger opioids, you hit that threshold more readily," Juurlink said of a high-dose regimen.
"And it may even be the case that men are more likely to take additional doses now and then without their doctor's permission," he speculated.
"Those are all factors which in theory could increase the risk of death."
Dr. Andrea Furlan, a physician at the Toronto Rehabilitation Institute who co-wrote the Canadian Opioid Guideline, said the ICES study provides useful information for prescribers about the risks for men compared to women.
At the same time, the "message of the guideline is to be careful with everyone, not just men," said Furlan, who was not involved in the study.
However, she questioned whether the study's findings reflect the situation in 2015, since the data show only what was happening up to 2010 — before the prescribing guideline was released.
"So we don't know what is the impact of having the guideline" on dose escalation and related deaths, she said. "So we need to see what's going on now."
Still, Furlan agrees that too many patients are continuing to be prescribed opioids and often at excessive doses.
Juurlink said patients need to understand that while opioids can help some people when used judiciously and at a low dose, they are still dangerous drugs.
"And I'd say the message for doctors is fairly unambiguous: think long and hard before you start a patient on long-term opioid therapy and try if at all possible to avoid escalating to high-dose therapy.
"There's no data to suggest that that's in a patient's best interest and you're very clearly exposing your patients to risk if you do that."
News from © The Canadian Press, 2015