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Publication Briefs

Opioids Do Not Result in Better Pain-Related Function or Pain Intensity Compared to Non-Opioid Drugs in Veterans with Chronic Pain

No previous randomized trials of opioid therapy have reported long-term pain, function, or quality of life outcomes. The Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial was a randomized trial that compared opioid therapy versus non-opioid medication therapy over 12 months for primary care patients with chronic back pain or hip or knee osteoarthritis pain. Investigators identified 240 Veterans with chronic pain (nearly every day for ≥6 months) that was moderate-to-severe despite analgesic use. Veterans were recruited from 62 Minneapolis VA primary care clinicians from June 2013 to December 2015. Patients were randomized to one of two intervention groups: opioid therapy or non-opioid medication therapy. Each intervention had its own prescribing strategy that included multiple medication options in three steps. In the opioid therapy group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the non-opioid group, the first step was acetaminophen or a non-steroidal anti-inflammatory drug. The primary outcome was pain-related function over 12 months, and the main secondary outcome was pain intensity. The primary adverse outcome was medication-related symptoms. Additional secondary outcomes included: quality of life, sleep disturbance, fatigue, depression, anxiety, adverse events, and opioid misuse.


  • The use of opioid therapy compared with non-opioid medication therapy did not result in significantly better pain-related function over 12 months.
  • Opioid therapy compared with non-opioid medication therapy resulted in significantly worse pain intensity over 12 months, but the importance of this is unclear because the magnitude was small.
  • Opioids caused significantly more medication-related adverse symptoms than non-opioid medications.

Overall, opioids did not demonstrate any advantage over non-opioid medications that could potentially outweigh their greater risk of overdose and other serious harms. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip/knee osteoarthritis pain.


  • Because primary outcomes were patient-reported, results are subject to potential reporting bias that would likely favor opioids.
  • There was an imbalance in pre-randomization treatment preference. Any effect of this imbalance would likely favor opioids.

This study was funded by HSR&D (IIR 11-125). Dr. Krebs, Ms. Gravely, and Mr. Nugent are part of HSR&D's Center for Chronic Disease Outcomes Research (CCDOR), Minneapolis.

PubMed Logo Krebs E, Gravely A, Nugent S, et al. Effect of Opioid vs. Non-Opioid Medications on Pain-Related Function in Patients with Chronic Back Pain or Hip or Knee Osteoarthritis Pain: the SPACE Randomized Clinical Trial. JAMA. March 6, 2018;319(9):872-82.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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