The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding) and by indirectness (differences between the population of interest and those studied: substantial secular changes in the management of rheumatoid arthritis may limit the applicability of the findings to patients in the current era).
A Cochrane review included 11 studies with a total of 672 subjects. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.
Seven studies were between 1 and 6 weeks in duration and assessed 6 different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate (1 study, n=20). Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (RR 1.44, 95% CI 1.03 to 2.03; 3 studies, n=324; NNT=6, 3 to 84) but not for the number of withdrawals due to inadequate analgesia (RR 0.82, 95% CI 0.34 to 2.0; 4 studies, n=345). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (OR 3.90, 95% CI 2.31 to 6.56; 4 studies, n=371; NNTH=4, 3 to 6); the pooled risk ratio for withdrawal due to adverse events was 2.67 (95% CI 0.52 to 13.75; 3 studies, n=331). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions.
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