Over the past 15 years, powerful opioid painkillers have been on the front lines of treatment for backache, headaches, and other chronic pain conditions in the United States. But over 100,000 overdose deaths later, physicians and policymakers are rethinking this approach. A flurry of reports in recent weeks suggests that the practice of treating routine chronic pain with opioids has outpaced the evidence.
Chronic pain affects one-third of Americans, and will afflict even more as the incidence of diseases such as diabetes, obesity, and arthritis rises in the aging population. This burden, combined with the unclear benefits but all too apparent risks long-term opioid use brings, requires more principled guidelines, argues a position paper published by the American Academy of Neurology (AAN) on September 30.
“Because organized medicine basically caused this problem, it’s really going to take organized medicine to reverse it,” said Gary Franklin of the University of Washington, Seattle, US, who wrote the paper, which is the first official caution regarding long-term opioid use for chronic pain from a major professional society.
In the same week, the National Institutes of Health (NIH) hosted a workshop to examine the issue, producing a summary that is open for commentary until October 17. Experts discussed the evidence, using as a key reference a new review of the literature commissioned by the Agency for Healthcare Research and Quality (AHRQ) on September 29. This report found no evidence for effectiveness of long-term opioid use for chronic pain, but a disquieting amount of evidence for harm, including overdoses and addiction.
Once reserved for short-term analgesia, or for easing pain in cancer patients at the end of their lives, opioid prescriptions began to surge in the late 1990s in the United States. Encouraged by a study finding that opioids could be used safely for several years to decrease pain in some people (Portenoy and Foley, 1986), some clinicians successfully advocated for extending opioid use to routine conditions such as back pain, headaches, or fibromyalgia. State laws relaxed limitations on prescribing opioids, and pain leaders taught that there was no ceiling on dosage, meaning that dosage should be increased to address tolerance.
“With that as a backdrop, it's not that surprising that doses went through the roof,” said Franklin, who was the first to document a rise in opioid overdose deaths (Franklin et al., 2005). “It becomes a vicious cycle.”
Between 1999 and 2010 over 100,000 people died from unintentional opioid overdoses. Deaths occurring in the highest risk age group of 35-54 years now outnumber deaths from gun and car accidents combined. This includes people who received prescriptions for the painkillers and people who obtained opioids illicitly for recreational use, often from friends or relatives with a prescription. Even those getting opioid prescriptions to treat chronic pain may start to abuse the drugs, making it hard to discern the number of deaths related to misuse.
Soldiers face an even greater risk of opioid abuse and overdose due to their high burden of chronic pain, according to a study published August 1 in JAMA Internal Medicine. A survey of soldiers returning from tours in Afghanistan or Iraq found that 44 percent reported chronic pain, and 23 percent of these said they had used opioids in the past month.
“Chronic pain and use of opioids carry the risk of functional impairment of America’s fighting force,” said a commentary accompanying the study.
More harm than good?
When taking opioids for chronic pain, there’s no clear end in sight. Of people who used opioids for at least three months to treat pain, 50 percent were still on the painkillers five years later (Martin et al., 2011). But it’s unclear how many get substantial pain relief. Physicians note that for some patients, long-term opioid treatment can provide adequate pain relief without undermining their quality of life. But for others it may be a situation of diminishing returns, in which escalated doses needed to numb pain increase disability due to dependence or addiction.
“We don't want to deny patients who could really benefit from chronic opioid therapy, but on the other hand, we want to minimize risk and harm,” said Judy Turner of the University of Washington, Seattle, US.
Yet so far, there are scant data for benefits. Turner and others put together the AHRQ report, which was ultimately based on 39 studies of opioid treatment lasting for at least one year. Not one study compared benefits from opioid use to either a non-opioid drug or a placebo control group. “But it's important to emphasize that the lack of evidence is not evidence for a lack of benefit,” Turner said. “We just don't know one way or another.”
The report did find evidence of harm, with opioid use raising risk of addiction, physical dependence, fractures, heart problems, and endocrine effects. Of people taking opioids for over a year, 0.6 to 8 percent ended up misusing or addicted to their medications, whereas 3 to 26 percent became physically dependent on them. Not surprisingly, higher opioid doses were also associated with increased risk of overdose.
The review also found little direction in the literature on whether the risk-benefit profile varied according to different types of chronic pain.
A way forward
Despite these research gaps, the AAN position paper urges the development of guidelines for clinicians. One recommendation is to set a “yellow flag” dosage of 80-120 mg per day (morphine-equivalent dose): when a patient exceeds this dose, the doctor must consult with a pain specialist.
Franklin helped develop a similar guideline in Washington, which in 2007 recommended 120 mg per day as a yellow flag dose. By 2010, a 27 percent decrease in opioid-related deaths was apparent. In 2011, the state also released tools to help doctors track dosage, pain, function, and risk in their patients. Other states have begun to institute similar guidelines.
Another approach may be to avoid opioids altogether. On September 25, the NIH announced funding $21.7 million worth of research on pain control methods that don’t involve drugs, including non-invasive brain stimulation, chiropractic care, and meditation. The projects focus on veterans because they suffer disproportionately from chronic pain.
The 13 funded projects stress pain management rather than just its abolition, said Josephine Briggs, director of the NIH’s National Center for Complementary and Alternative Medicine (NCCAM), which funded the grants, along with the National Institute of Drug Abuse and the Veterans Administration. “Reducing pain is important, but we also need to learn about ways to help patients keep the pain from interfering with their important life activities,” she said.
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