Patients and clinicians can choose from several treatment options to address acute pain from non-low back musculoskeletal injuries.
To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs).
MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020.
Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks’ duration from non-low back musculoskeletal injuries.
Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence).
Only English-language studies were included. The number of head-to-head comparisons was limited.
Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms.
National Safety Council. (PROSPERO: CRD42018094412).

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