The evidence supporting the use of opioid analgesia in osteoarthritis is poor, but available trial data show that, compared with placebo, opioid analgesics reduce pain in people with osteoarthritis of the knee. There are a lack of trials comparing the efficacy and safety of opioids with other symptomatic treatments for osteoarthritis, and there are virtually no good studies using opioids in people with peripheral joint osteoarthritis, so the benefits of opioids in different types of osteoarthritis remains unclear. There is little evidence to suggest that increasing the opioid dose improves the effect. There are also few data comparing different opioid formulations or routes of administration. The adverse effects of opioids are a concern, especially in elderly people.

• The National Institute for Health and Clinical Excellence (NICE) looked at studies that investigated the efficacy and safety of opioids or opioid–paracetamol compounds compared with other treatment options, with respect to symptoms, function, and quality of life in adults with osteoarthritis. Two systematic reviews were appraised [Cepeda et al, 2006; Bjordal et al, 2007].
• A Cochrane review (11 RCTs, n = 1019) compared the efficacy and safety of tramadol or tramadol/paracetamol with placebo or active control in people with osteoarthritis [Cepeda et al, 2006]. Literature searches were performed up to August 2005.
• Efficacy of opioid analgesics compared with placebo:
• A meta-analysis of three RCTs (n = 749), ranging from 14–91 days, compared the effect of tramadol, tramadol–paracetamol in combination, and paracetamol alone in people with osteoarthritis (mainly of the knee).
• In terms of pain intensity, the analysis found a mean difference of –8.47 (95% CI –12.1 to –4.9, p < 0.00001), favouring the opiod/opioid–paracetamol combination.
• Tramadol was found to significantly reduce pain intensity and total WOMAC score compared with placebo:
• Pain intensity (WMD –8.47, 95% CI –12.05 to –4.90)
• WOMAC score (WMD –0.34, 95% CI –0.49 to –0.19)
• RR 1.37, 95% CI 1.22 to 1.55
• Efficacy of opioid analgesics compared with each other:
• Three RCTs were evaluated that compared tramadol versus dihydrocodeine, dextropropoxyphene, and pentazocine. Tramadol increased the likelihood of a moderate improvement by 38% compared with dextropropoxyphene, and by 150% compared with pentazocine (absolute data and p-value not reported).
• Safety of opioid analgesics compared with placebo:
• The Cochrane review found that tramadol increased the risk of developing major adverse events by 2.6 times (95% CI 2.0 to 3.6) compared with placebo:
• Tramadol — 143/710 (20%)
• Placebo — 49/626 (8%)
• Number needed to harm: 8 (95% CI 7 to 12)
• Safety of opioid analgesics compared with each other:
• The systematic review found that tramadol caused significantly more adverse events than dextropropoxyphene:
• Tramadol — 48/135 (36%)
• Dextropropoxyphene — 14/129 (11%)
• Number needed to harm: 6 (95% CI 4.4 to 12.0)
• Tramadol was also found to cause fewer adverse events than pentazocine, but the p-value was not reported:
• Tramadol — 9/30 (30%)
• Pentazocine — 11/30 (37%)
• A second systematic review (63 RCTs, n = 14,060) investigated the short-term pain relieving effects of seven commonly used drugs in people with osteoarthritis of the knee [Bjordal et al, 2007].
• Efficacy of opioid analgesics compared with placebo:
• In people with moderate-to-severe pain, opioids had maximum efficacy at 2–4 weeks compared with placebo:
• Six RCTs (n = 1057), mean difference 10.5 (95% CI 7.4 to 13.7).
• Safety of opioid analgesic compared with placebo:
• Withdrawal rate — opioids were associated with high withdrawal rates (20–50%) compared with placebo (about 10%).

[National Collaborating Centre for Chronic Conditions, 2008]