MINNEAPOLIS — The VA has struggled to reduce the use of opioids in chronic pain patients over the long term, primarily because of concerns about risk of addiction and other adverse effects. A new veterans study provides another good reason: The therapy really isn’t that effective.

Important new research noted that, while opioids often are prescribed for chronic pain for extended periods of time, evidence has been limited on how effective they really are.

The new study published in the Journal of the American Medical Association (JAMA) sought to determine effectiveness and found that opioid medications were no better than nonopioid medications at improving pain that interfered with activities such as walking, work and sleep.

The study, led by researchers from the Minneapolis Veterans Affairs Health Care System, was conducted over a year with veterans suffering from chronic back pain or hip or knee osteoarthritis pain.

Included were 240 patients seeking care from 2013 to 2015, with follow-up ending in 2016. Participants, who averaged 58.3 years old and were 87% male, were recruited from 62 Minneapolis VA primary care clinicians who were affiliated with the Minneapolis VAMC, including clinics in the main medical center building and four outpatient clinics in the greater Minneapolis-Saint Paul metropolitan area. Potentially eligible patients were identified by searching the electronic health record (EHR) for back, hip or knee pain diagnoses at a primary care visit in the prior month, with study personnel screening patients by telephone and then conducting a focused chart review.

For the trial, both interventions—opioid and nonopioid medication therapy—followed a treat-to-target strategy which sought to improve pain and function. In the opioid group, the first step was immediate-release morphine, oxycodone or hydrocodone/acetaminophen.

For the nonopioid group, meanwhile, the first step was acetaminophen or a nonsteroidal anti-inflammatory drug. Individual patient response determined when medications were changed, added, or adjusted, study authors noted.

No Significant Difference

Results indicated that the two groups did not significantly differ on pain-related function over 12 months (overall P = .58), with mean 12-month BPI interference of 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]).

Despite the avoidance of narcotics, pain intensity was significantly improved in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]), the researchers pointed out. The opioid group, meanwhile, had significantly more adverse medication-related symptoms over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]).

“Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months,” study authors concluded. “Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.”

The authors, led by Erin E. Krebs, MD, MPH, of the1 Center for Chronic Disease Outcomes Research at the Minneapolis VAMC and the University of Minnesota Medical School, noted that, actually, nonopioid treatment was associated with significantly better pain intensity. They added, however, that the clinical importance of the finding was unclear, partly because the magnitude was so small—0.5 points on the 0-10 BPI severity scale—and less than the MCID of 1.0.

At the same time, researchers emphasized that opioids did not demonstrate any advantage over nonopioid medications that could potentially outweigh their greater risk of harms, which included causing significantly more medication-related adverse symptoms than nonopioid medications.

The study team said that slight differences also called into question the importance of findings related to secondary outcomes. Only anxiety symptoms were found to be statistically better in the opioid group.

“This finding is consistent with the role of the endogenous opioid system in stress and emotional suffering,” study authors write. “The importance of this finding is uncertain because the magnitude of the difference in anxiety was small and the overall level of anxiety was low (9% of patients had moderate severity anxiety symptoms at baseline).”

Overall, however, they said that pain-related function improved for most patients in each group. “Poor pain outcomes associated with long-term opioids in observational studies may be attributable to overprescribing and insufficient pain management resources rather than to direct negative effects of opioids,” the researchers suggested.

While the trial didn’t have sufficient statistical power to estimate rates of death, opioid use disorder or other serious harms associated with prescribed opioids, the participants had characteristics similar to those of patients receiving opioids in VA primary care, including patients with depression and post-traumatic stress disorder.

In addition, flexibility of treatment within assigned groups kept patients in the study. The treat-to-target approach was more like real-world clinical practice than approaches comparing single drugs or fixed dosages, study authors pointed out.
The study cited recent opioid prescribing guidelines, which recommend keeping daily dosages low. “This study was designed to identify the medication regimen with the best balance of benefits and tolerability for each patient and allowed treatment with a range of low to moderately high opioid dosages,” study authors noted.

Among the limitations of the study were that results were patient-reported and that patients with physiological opioid dependence due to ongoing opioid use were excluded, so results do not apply to them.


1Krebs EE, Gravely A, Nugent S, et. al. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain—The SPACE Randomized Clinical Trial. JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899