Abstract: We included 16 trials, with a total of 2144 participants. Two studies included children only. The other 14 studies included predominantly young adults, of whom over 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, one was at high risk of bias due to incomplete outcome data, and four were at high risk of selective outcome reporting bias. The evidence was usually either low quality or very low quality, reflecting study limitations, indirectness such from as suboptimal dosing of single comparators, imprecision, or one or more of these. Thus we are either uncertain or very uncertain of the estimates. Nine studies, involving 991 participants, compared NSAIDs with paracetamol. While tending to favour paracetamol, there was a lack of clinically important differences between the two groups in pain at less than 24 hours (377 participants, 4 studies; moderate-quality evidence), at days 1 to 3 (431 participants, 4 studies; low quality), and at day 7 or over (467 participants, 4 studies; low quality). A similar lack of difference between the two groups applied to swelling at day 3 (86 participants, 1 study; very low quality) and at day 7 or over (77 participants, 1 study; low quality). There was little difference between the two groups in return to function at day 7 or over (316 participants, 3 studies; very low quality): based on an assumed recovery of function of 804 per 1000 participants in the paracetamol group, 8 fewer per 1000 recovered in the NSAID group (95% confidence interval (CI) 80 fewer to 73 more). There was low-quality evidence of a lower risk of gastrointestinal adverse events in the paracetamol group: based on an assumed risk of gastrointestinal adverse events of 16 per 1000 participants in the paracetamol group, 13 more participants per 1000 had a gastrointestinal adverse event in the NSAID group (95% CI 0 to 35 more). Four studies, involving 958 participants, compared NSAIDs with opioids. Since a study of a selective COX-2 inhibitor NSAID (valdecoxib) that was subsequently withdrawn from the market dominates the evidence for this comparison (706 participants included in the analyses for pain, function and gastrointestinal adverse events), the applicability of these results is in doubt and we give only a brief summary. There was low quality evidence for a lack of clinically important differences between the two groups regarding pain at less than 24 hours, at days 4 to 6, and at day 7. Evidence from single studies showed a similar lack of difference between the two groups for swelling at day 3 (68 participants) and day 10 (84 participants). Return to function at day 7 or over favoured the NSAID group (low-quality), and there were fewer gastrointestinal adverse events in the selective COX-2 inhibitor NSAID group (very low quality). Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is partly in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. While the point estimates favoured NSAID, the very low-quality evidence did not show a difference between the two interventions in the numbers with little or no pain at day 1 (51 participants, 1 study), day 3 (149 participants, 2 studies), or day 7 (138 participants, 2 studies). Very low-quality evidence showed a similar lack of difference between the two groups applied to swelling at day 3 (reported in two studies) and at day 7 (reported in two studies), in return to function at day 7 (89 participants, 1 study), and in gastrointestinal adverse events (141 participants, 3 studies). No studies compared NSAIDs with complementary and alternative medicines, and no study reported re-injury rates. There is generally low- or very low-quality but consistent evidence of no clinically important difference in analgesic efficacy between NSAIDs and other oral analgesics. There is low-quality evidence of more gastrointestinal adverse effects with non-selective NSAID compared with paracetamol. There is low- or very low-quality evidence of better function and fewer adverse events with NSAIDs compared with opioid-containing analgesics; however, one study dominated this evidence using a now unavailable COX-2 selective NSAID and is of uncertain applicability. Further research is required to determine whether there is any difference in return to function or adverse effects between both non-selective and COX-2 selective NSAIDs versus paracetamol.

Plain-language summary: The evidence available for most outcomes was either low or very low quality. This means that we are unsure of the reliability of these results. We found no evidence for an important difference between NSAIDs and paracetamol for people with strains, sprains and bruises for pain relief, swelling or return to function at seven days or over. However, there was some evidence that people treated with NSAIDs had slightly more side-effects related to the stomach or intestines. Although there was some evidence to suggest a greater return to function at seven days and fewer side-effects for people with sprains, strains and bruises using an NSAID compared with an opioid, we cannot say if this would apply to drugs that are currently available. This is because most of the evidence came from a study that tested an NSAID that is no longer on the market. We found no evidence for an important difference between NSAIDs and a combination of paracetamol and opioid for people with sprains, strains and bruises regarding pain relief, swelling, return to function at seven days or over, or gut-related side-effects. However, the combination painkiller used in the studies is not now in common use. This means that we cannot be sure that these results would currently apply. We found no studies comparing NSAIDs and complementary and alternative medicines. Also, no studies looked at the risk of re-injury after treatment. This review found low or very low-quality but consistent evidence showing no important difference between NSAIDs and paracetamol, opioids or a combination of paracetamol and opioid in pain or swelling after a soft tissue injury. There is low-quality evidence of more gut-related complications with NSAIDs compared with paracetamol. Although there is either low- or very low-quality evidence of better function and fewer adverse events with NSAIDs compared with opioid-containing analgesics, one study dominated this evidence using a now unavailable NSAID and is therefore of uncertain applicability. Further research is required to determine whether there is any difference in return to function or adverse effects between different types of NSAIDs versus paracetamol.