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Opioid benefit small in chronic noncancer pain

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Opioids role very limited in noncancer pain

This meta-analysis suggests that most patients receiving opioids for chronic noncancer pain will not benefit from them, according to Michael A. Ashburn, MD, MPH, and Lee A. Fleisher, MD.

Dr. Lee A. Fleisher

It is time for physicians to redouble efforts to improve the process of care when prescribing opioids,” Dr. Ashburn and Dr. Fleisher wrote in an editorial commenting on the meta-analysis.

Outcomes of the study, which suggest opioids produce modest benefits over placebo in pain and physical functioning, and no difference in pain relief versus NSAIDs, are likely to represent the best case scenario, the authors wrote.

That’s because most trials excluded patients with substance use disorder and nearly half excluded patients with mental illness or those taking psychotropic medications, they explained.

In the clinical setting, many patients will have depression, anxiety, sleep-disordered breathing, and other conditions that could increase the potential risk of harm with opioids, according to the authors.

That said, when proper monitoring is incorporated into care, opioid treatment can be safe and effective for selected patients. “Diligent opioid prescribing to carefully selected patients will lower the risk of harm to patients, their families, and the community,” the authors wrote in their editorial.

Dr. Ashburn and Dr. Fleisher are with the department of anesthesiology and critical care at the University of Pennsylvania, Philadelphia. Their editorial appears in JAMA. Dr. Ashburn reported receiving personal fees from Teva, the Department of Justice, the Attorney General for the State of Maryland, the Department of State for the Commonwealth of Pennsylvania, the Montgomery County District Attorney, and the Carolinas Pain Society. He also reported several patents related to drug delivery systems and methods.



Compared with placebo, opioids provide very modest improvements in chronic noncancer pain and physical functioning that decrease over time, according to the authors of a systematic review and meta-analysis of nearly 100 randomized clinical trials.

Dr. Lee Fleisher

There was little difference in pain control between opioids and nonopioid alternatives such as NSAIDs in a subset of nine such comparative trials, reported the authors, led by Jason W. Busse, DC, PhD, of the department of anesthesia at McMaster University, Hamilton, Ont.

Pain benefits of opioids decreased over time in longer trials, possibly because of opioid tolerance or hyperalgesia, a condition marked by hypersensitivity to pain. “A reduced association with benefit over time might lead to prescription of higher opioid doses and consequent harms,” Dr. Busse and his coauthors wrote in JAMA.

The meta-analysis included 96 randomized clinical trials including 26,169 patients with chronic noncancer pain.

Opioid treatment did significantly improve pain and physical function versus placebo, though the magnitude of benefit was small, according to the investigators. The reduction in pain was –0.69 cm on a 10-cm visual analog scale (P less than .001), based on high-quality evidence from 42 randomized, controlled trials that followed patients for at least 3 months.

The improvement in physical functioning was likewise significant but small at 2.04 out of 100 points on the SF-36 physical component score (P less than .001). Emotional and role functioning were not significantly improved by opioid use.

Opioid use was linked to increased vomiting incidence versus placebo, with a relative risk of 4.12 (95% CI, 3.34-5.07; P less than .001) for patients in “nonenrichment” trials – those studies that included all patients regardless of whether or not they reported lack of improvement or had substantial adverse events during a study run-in period.

Nausea, constipation, dizziness, drowsiness, pruritus, and dry mouth were also linked to opioid use as compared with placebo, Dr. Busse and his colleagues reported.

The benefit of opioids and nonopioid alternatives appeared to be similar in this meta-analysis, though the available evidence from comparative studies was of low to moderate quality, the authors advised.

In moderate-quality evidence from nine clinical trials of opioids versus NSAIDs including 1,431 patients, there was no difference in pain relief between the two interventions, the investigators said. Moreover, comparisons of physician functioning also suggested no difference, while opioids were associated with more vomiting.

Both tricyclic antidepressants and synthetic cannabinoids offered similar pain relief, compared with opioids, based on low-quality clinical trial evidence, they added, while moderate-quality evidence suggested opioids offered superior pain relief, compared with anticonvulsants.

Support for the study came from the Canadian Institutes of Health Research and Health Canada. One study coauthor reported receiving personal fees from Purdue Pharma and the Nova Scotia College of Physicians and Surgeons.

SOURCE: Busse JW et al. JAMA. 2018;320(23):2448-60.

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