New AAN Position Statement on Opioids for Noncancer Pain

Pauline Anderson

September 29, 2014

For mild to moderate pain conditions, such as headache, fibromyalgia, and chronic low back pain, the risks for overdose, addiction, or serious adverse effects associated with long-term use of opioids likely outweigh the benefits, a new position paper from the American Academy of Neurology (AAN) concludes.

For conditions like rheumatoid arthritis, sickle-cell disease, and neuropathic pain, the paper determines that the long-term risks of opioids are unclear.

"For the most severe chronic pain conditions, we still don't know in whom the risk-benefit will be worth it, but clinicians should at least try to keep the dose low, and maybe even use opioids intermittently," the paper's lead author, Gary Franklin, MD, MPH, research professor, Departments of Occupation and Environmental Health Sciences, Neurology, and Health Services, University of Washington, Seattle, told Medscape Medical News.

When treating patients with chronic noncancer pain (CNCP) who continue to take opioids, doctors could use guidance on dosing, tools to screen for risks, and advice on how to monitor patients for early signs of adverse events and misuse, said Dr. Franklin.

The document is published in the September 30 issue of Neurology.

Increasing Doses

The paper comes in the wake of a growing national epidemic in opioid-related deaths. Between 1999 and 2010, more than 100,000 Americans died of opioid overdoses. This, said Dr. Franklin, far exceeds the 58,000 US military casualties of the Vietnam War.

Opioid doses have increased dramatically and quickly during that period, said Dr. Franklin. The average daily dose among a group of injured workers, for example, has gone from 80 to over 140 mg/day MED (morphine equivalent dose).

Dr. Franklin links this increase to advice of "pain leaders" and advocacy groups that lobbied states to pass laws that liberalized the use of opioids for CNCP.

"These state laws pretty much enshrined the unproven theories or assumptions that there was no ceiling on dose and that the way to treat tolerance is to keep increasing the dose," said Dr. Franklin.

The premise that tolerance can be overcome by dose escalation is now seriously questioned, he added.

High opioid doses are strongly related to huge increases in risks for overdose. "Only when the doses went up did we start to see most of the overdoses," said Dr. Franklin. "There's a very strong proven relationship between dose and overdose events, including death."

He cited a study (Ann Intern Med. 2010;152:85-92) that showed a 9-fold increased risk for overdose at doses exceeding 100 mg/d MED compared with doses below 20 mg/d MED in patients with CNCP. Two additional "high-quality" studies have corroborated the substantially increased risk associated with doses at or above 100 to 120 mg/d MED.

And higher doses don't make patients better, stressed Dr. Franklin. He referred to a randomized trial of patients in the Department of Veterans Affairs in southern California that showed no differences between patients in whom doses were "ramped up" and in those in whom they weren't.

Dr. Franklin also pointed to evidence suggesting that a significant proportion of deaths attributable to opioids are due to overprescribing as well as misuse and diversion of these drugs.

Not only are opioids linked to overdose deaths, but they come with sometimes significant adverse effects, including constipation, nausea, vomiting, dizziness, and drowsiness. Other serious, long-term consequences of opioid use include infertility, immunosuppression, falls and fractures in older adults, neonatal abstinence syndrome, cardiac issues, and opioid-induced hyperalgesia.

Dependence and Addiction

There's also the issue of physical dependence and addiction among opioid users. Although the extent of the problem is unknown, it's likely that many more patients than previously reported develop these serious complications, according to Dr. Franklin. Half the patients taking opioids for at least 3 months are still taking them 5 years later — and that goes up to 85% in those with comorbid mental illness, he said.

Dependence seems to feed into disability. Dr. Franklin referred to a study showing that getting just 7 days' worth of opioid medication in the first 6 weeks following a work-related injury doubles the risk of being on disability a year later.

"So in our view, opioids are not only contributing to the onset of disability but are helping to perpetuate disability," he said.

Most problematic, he writes in his paper, "is the lack of a useful case definition for any of these dependent states, making it challenging for an uninitiated prescribing provider to identify and intervene appropriately."

According to Dr. Franklin, the AAN is one of the first groups in organized medicine "to try to reverse" the epidemic of opioid-related deaths.

States, too, are starting to respond to the urgent public health problem. For example, Washington, along with the Centers for Disease Control and Prevention, has "yellow flag" guidelines recommending that a prescriber seek consultation if a patient reaches 120 mg/d MED and if pain and function haven't substantially improved. Other states are pursuing similar policies.

The Washington guideline has been updated to include tools for prescribing opioids to patients with CNCP that allow clinicians to, for example, track pain and function, screen for past and current substance abuse and depression, and calculate daily MED in real time using a Web-based application.

A new Washington guideline, specific to workers' compensation, includes a tapering algorithm for patients receiving high doses who haven't demonstrated meaningful improvement in function, and recommendations for perioperative opioid use in patients receiving chronic opioid analgesic therapy in whom elective surgery is planned.

Risk Evaluation and Mitigation Strategies

Elsewhere, the US Food and Drug Administration (FDA) has implemented risk evaluation and mitigation strategies for extended-release and long-acting Schedule II opioids. The FDA has also moved to up-schedule hydrocodone products to Schedule II and to change labeling on extended-release/long-acting opioids to reserve their use for patients with more severe pain that requires around-the-clock dosing.

The White House Office of National Drug Control Policy has provided national guidance, emphasizing prescriber education and enhanced capacity of state Prescription Drug Monitoring Programs (PDMPs) that allow prescribers to check on dispensed sources of all controlled substances.

However, these programs, said Dr. Franklin, are underfunded, underused, and not interoperable across states lines or healthcare systems.

"In a lot of states, less than 30% of doctors who could and should be using the program are using it," said Dr. Franklin, adding that there's evidence that some doctors don't even do random urine testing.

"It's a matter of clinicians not understanding that these are crucial best practices; you could even call them universal precautions."

To help illustrate the extent of the problem, Dr. Franklin pointed to an as-yet unpublished study he and his colleagues carried out that found most people admitted to the hospital with an opioid overdose continued to receiving an opioid — and some later died.

Dr. Franklin identified a need for more studies looking at the long-term benefits and harms of opioids for CNCP. Although there's evidence for substantial pain relief in the short term — an average of 5 weeks, according to the trials — no substantial evidence suggests maintenance of pain relief over longer periods of time or improved physical function, Dr. Franklin writes.

Other research gaps, he said, include the extent, intensity, and quality of urine drug testing; genotyping to determine whether response to opioid therapy can or should be more individualized; and how to identify patients who benefit from long-term opioid use but are not adversely affected by long-term adverse effects.

Safety Steps

For patients still receiving opioids for CNCP, clinicians can take several steps to safely and effectively use these drugs, said Dr. Franklin. For example, he recommends that they do the following:

  • Draft an opioid treatment agreement with patients (which should include such things as carrying out random drug screening);

  • Assess prior or current abuse or misuse of alcohol and illicit drugs and heavy tobacco use;

  • Screen for depression;

  • Prudently use random urine drug screening (to identify cases of diversion and nonprescribed drugs);

  • Avoid prescribing concomitant sedative-hypnotics or benzodiazepines;

  • Track pain and function at every visit;

  • Track daily MED using an online dosing calculator;

  • Seek help if MED reaches 80 to 120 mg and pain and function have not substantially improved; and

  • Use the state PDMPs to monitor all sources of controlled substances.

Patients who are misusing opioids or obtaining them from multiple prescribers may be discharged from the practice, said Dr. Franklin.

More Research

Reached for a comment, Lynn Webster, MD, immediate past president, American Academy of Pain Medicine (AAPM) and vice president, scientific affairs, PRA Health Science, said the AAN document "summarizes the risks of opioids" and reinforces the position that opioids need to be prescribed with caution.

"Opioids are not going to be helpful with many patients, and if we're going to prescribe opioids, we need to be cognizant of the potential harm."

Dr. Webster noted that while the paper presented some evidence, albeit weak evidence, that opioids can help a subset of the population, it concluded that these drugs may not be effective long term for many pain conditions.

"Clearly, we need safer and more effective therapy than opioids because we are not doing a very good job of treating millions of Americans with serious disabling pain, many of whom are suicidal," said Dr. Webster.

"We don't have good therapies; unfortunately, opioids are about the only treatment that insurance carriers will pay for. So ultimately, we need a lot more research so that one day we can replace opioids."

Dr. Franklin has disclosed no relevant financial relationships.

Neurology. 2014;83:1277-1284. Abstract

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