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People with long-term back pain, or osteoarthritis of their hips or knees, do not get better pain relief from opioid drugs and are more likely to get side effects than those who take paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs), like naproxen or ibuprofen.

A US study assigned 240 patients to either opioid or non-opioid pain relief drugs and measured their pain over 12 months. Those who were assigned opioid drugs had less relief of their pain and also were more likely to have side-effects related to their medication.

The findings may surprise some doctors and patients with long-term pain, because of the widely held belief that opioids have a stronger pain-relieving effect. Concerns have been raised in recent years that too many people are prescribed potentially-addictive opioids.

The findings support current guidance that opioids should not be used as first-line pain relief drugs for osteoarthritis. However, clinicians should also be aware of the risk of side effects of other drugs too.

Why was this study needed?

Long-term back pain and hip and knee pain from osteoarthritis are common and debilitating conditions. An estimated 278,000 workers in the UK suffered from musculoskeletal pain in the back or lower limbs in 2016/17.

The amounts of opioid drugs prescribed in the UK increased between 2010 and 2014, although we don't know how many of these prescriptions were for long-term pain and how many for the appropriate short-term relief of pain in cancer or just after surgery for example.

UK guidelines discourage the use of opioids for long-term pain relief, because of the potential for addiction and death from overdose. However, opioids are more widely used in other countries including the US, leading to what has been described as an “epidemic” of opioid use and abuse.

What did this study do?

Researchers recruited 265 adults with chronic back pain, hip or knee osteoarthritis, attending primary care clinics in the US to take part in this pragmatic randomised trial. After 25 were excluded or declined to participate, 240 were assigned either to opioid or non-opioid medication.

Each group had a prescribing strategy with three escalating steps which clinicians could use to bring pain under control.

For opioids, these were:

  1. immediate release morphine, hydrocodone/paracetamol, or oxycodone
  2. sustained action morphine or sustained action oxycodone
  3. transdermal fentanyl.

For non-opioids, these were:

  1. paracetamol and NSAIDs
  2. nortriptyline, amitriptyline, gabapentin or topical analgesics
  3. pregabalin, duloxetine or tramadol.

The study was not powered to estimate serious harms associated with opioids, such as death or opioid abuse.

The main outcome of interest was whether pain interfered with daily life and was assessed with the 7-item Brief Pain Inventory interference scale, where higher scores indicate worse pain. This trial used a 1-point difference as the minimally clinical important difference on this scale.

What did it find?

  • There was no relevant clinical difference in pain-related ability to function between people assigned to opioids and people assigned to non-opioids. Pain improved in both groups, from an average 5.4 points at the start of the study in the opioid group to 3.4 points at the end, while the non-opioid group went from average 5.5 points at the start to 3.3 at the end (between-group difference 0.1, 95% confidence interval [CI] -0.5 to 0.7).
  • Pain intensity was also not clinically different in the non-opioid group at the end of the study. On a scale of 1 to 10, pain severity at the end of the study was 4.0 in the opioid group and 3.5 in the non-opioid group (between-group difference 0.5, 95% CI 0.0 to 1).
  • People in the opioid group had more medication-related symptoms over 12 months of treatment (symptom score for the group at 12 months 1.8 on a checklist of 0 to 19 where higher score indicates more symptoms, compared with 0.9 for the non-opioid group).
  • There was no difference in adverse outcomes such as hospital visits or measures of opioid misuse.

What does current guidance say on this issue?

A NICE guideline (updated in 2014) on the treatment of osteoarthritis says: “Paracetamol and/or topical non-steroidal anti-inflammatory drugs (NSAIDs) should be considered ahead of oral NSAIDs, cyclo-oxygenase 2 (COX-2) inhibitors or opioids.” The guideline goes on: “If paracetamol or topical NSAIDs are insufficient for pain relief for people with osteoarthritis, then the addition of opioid analgesics should be considered.”

Regarding low back pain, NICE says (in 2016): “Consider oral non-steroidal anti-inflammatory drugs (NSAIDs) for managing low back pain, taking into account potential differences in gastrointestinal, liver and cardio-renal toxicity, and the person's risk factors, including age,” and “Do not offer opioids for managing chronic low back pain.”

What are the implications?

The results of this pragmatic trial suggest there is little benefit to be gained from initiating opioid treatment for people with chronic back pain or pain from osteoarthritis of the hip or knee. The trial did not assess the effects of opioids added to paracetamol or anti-inflammatories.

The message that opioid pain relief medications are no better than simple analgesics such as paracetamol, or anti-inflammatory medicines, and may have unwanted side effects, might surprise some people.

While side effects were not listed in the study, common opioid side effects include constipation and drowsiness as well as a risk of addiction in long-term use.

Chronic pain continues to be a challenge for clinicians. However, the study confirms that opioid medication is unlikely to be a useful answer to that problem.

Citation and Funding

Krebs 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):872-82.

The study was funded by the US Department of Veterans Affairs Health Services Research and Development Service.



NICE. Low back pain and sciatica in over 16s: assessment and management. NG59. London: National Institute for Health and Care Excellence; 2016.

NICE. Osteoarthritis: care and management. CG177. London: National Institute for Health and Care Excellence; 2014.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre


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