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#64 Opioids and Osteoarthritis: Weighing Benefits and Risks

What is the evidence for opioids as a treatment for osteoarthritis (OA)?

In OA, there are no trials to demonstrate long-term improvements in pain or function with opioids. In elderly patients with OA, the risks of opioids may be worse than the risks of NSAIDs. Opioids should not be routinely used in OA, but if necessary, they should be used for short courses in carefully selected patients. 

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Benefits: No high-quality evidence that opioids improve function more than non-opioid analgesics.1,2 
  • Non-tramadol opioids: Systematic review3 of 22 Randomized Controlled Trials (RCTs) with 8,275 OA patients, median 4-weeks treatment (maximum six months). 
    • More patients reported >50% improvement in pain versus placebo, Number Needed to Treat (NNT)=10. 
      • Median dose: 59 mg morphine-equivalent per day; higher doses did not increase benefits. 
      • Smaller benefits seen in trials >4 weeks. 
    • Function improved 0.6 out of 10 points more versus placebo, NNT=12. 
  • Tramadol: 
    • Systematic review4 of 11 RCTs with 1,939 OA patients, maximum 12-week treatment. 
      • More patients reported at least “moderate” improvement in pain versus placebo, NNT=6. 
    • RCTs have not demonstrated a difference in pain between tramadol and NSAIDs.4,5,6 
  • Harms:  
    • Side-effects cause one in 6-8 to stop treatment.3,4 
    • Cohort study of 12,840 arthritis patients (mean age 80) comparing opioids to NSAIDs:7 
      • Higher risk of fracture when prescribed opioids versus NSAIDs, Number Needed to Harm (NNH)=26. 
      • Opioids also associated with increased risk of cardiovascular events, hospitalizations, and mortality (NNH=17-27). 
      • Limitations: Opioid risk likely exaggerated by selection bias and confounding. 
  • Only small differences in pain are seen between oral OA treatments and placebo (standard mean difference [95% Confidence Intervals]): Acetaminophen 0.13 (0.04-0.22),8 NSAIDs 0.23 (0.15-0.31),9 and opioids 0.28 (0.20-0.35).3  
    • Consider having patients evaluated for joint replacement if pain from OA is severe, as surgery improves quality of life.10 
  • International OA guidelines recommend opioids only in exceptional cases.11 
  • Risks of opioids are dose-dependent: 
    • >100 mg morphine-equivalent per day (e.g. approximately hydromorphone 20 mg or oxycodone 66 mg) is associated with increased risk of opioid-related mortality.12,13 
    • Prescription opioids are a common source of misuse,14 and most opioid overdose deaths occur in individuals who were prescribed opioids.15 
updated july 22,  2016 by Ricky D. Turgeon BSc(Pharm) ACPR PharmD

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  • G. Michael Allan MD CCFP
  • Irfan Dhalla MD FRCPC
  • Noah Ivers MD CCFP

1. Furland AD, Sandoval JA, Mailis-Gagnon A, et al. CMAJ. 2006; 174:1589-94.

2. Ballantyne JC, Shin NS. Clin J Pain. 2008; 24:469-78.

3. Da Costa BR Nuesch E, Kasteler R, et al. Cochrane Database Syst Rev. 2014; (9):CD003115.

4. Cepeda MS, Camargo F, Zea C, et al. Cochrane Database Syst Rev. 2006; (3):CD005522.

5. Beaulieu AD, Peloso PM, Haraoui B, et al. Pain Res Manage. 2008; 13:103-10.

6. DeLemos BP, Xiang J, Benson C, et al. Am J Ther. 2011; 18:216-26.

7. Solomon DH, Rassen JA, Glynn RJ, et al. Arch Intern Med. 2010; 170:1968-76.

8. Towheed TE, Maxwell L, Judd MG, et al. Cochrane Database Syst Rev. 2006; (1):CD004257.

9. Bjordal JM, Ljunggren AE, Klovning A, et al. BMJ. 2004; 329:1317.

10. Skou ST, Roos EM, Laursen MB, et al. N Engl J Med. 2015; 373:1597-606.

11. Zhang W, Moskowitz RW, Nuki G, et al. Osteoarthritis Cartilage. 2007; 15:981-1000.

12. Gomes T, Mamdani MM, Dhalla IA, et al. Arch Intern Med. 2011; 171:686-91.

13. Bohnert AS, Valenstein IM, Bair MJ, et al. JAMA. 2011; 305:1315-21.

14. Sproule B, Brands B, Li S, Catz-Biro L. Can Fam Physician. 2009; 55:68-9.e1-e5.

15. Dhalla IA, Mamdani MM, Sivilotti ML, et al. CMAJ. 2009; 181:891-6.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 22/07/2016

By: Ricky D. Turgeon BSc(Pharm) ACPR PharmD


Evidence Updated: New evidence; Bottom Line: No change.

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