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Original Investigation
March 6, 2018

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis PainThe SPACE Randomized Clinical Trial

Author Affiliations
  • 1Center for Chronic Disease Outcomes Research, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota
  • 2Department of Medicine, University of Minnesota Medical School, Minneapolis
  • 3Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, Minneapolis, Minnesota
  • 4Center for Health Information and Communication, Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana
  • 5Department of Medicine, Indiana University School of Medicine, Indianapolis
  • 6Regenstrief Institute, Indianapolis, Indiana
JAMA. 2018;319(9):872-882. doi:10.1001/jama.2018.0899
Key Points

Question  For patients with moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use, does opioid medication compared with nonopioid medication result in better pain-related function?

Findings  In this randomized clinical trial that included 240 patients, the use of opioid vs nonopioid medication therapy did not result in significantly better pain-related function over 12 months (3.4 vs 3.3 points on an 11-point scale at 12 months, respectively).

Meaning  This study does not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.


Importance  Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.

Objective  To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects.

Design, Setting, and Participants  Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized.

Interventions  Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response.

Main Outcomes and Measures  The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19).

Results  Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]). Pain intensity was significantly better 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]). Adverse medication-related symptoms were significantly more common in the opioid group 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]).

Conclusions and Relevance  Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.

Trial Registration  clinicaltrials.gov Identifier: NCT01583985