Subcutaneous Administration of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Pain Management: A Systematic Review and Meta-Analysis.

This review aimed to evaluate the efficacy and safety of subcutaneous nonsteroidal anti-inflammatory drugs (NSAIDs). We searched CENTRAL, MEDLINE, Embase, trial registries, and Google Scholar until December 19, 2024. Eligible studies were randomized controlled trials (RCTs) in adults comparing subcutaneous NSAIDs with other routes of administration, placebo, no treatment, or other drugs. The primary outcome was pain intensity; secondary outcomes were rescue medication use and adverse events. We assessed risk of bias using the Risk of Bias 2 tool. Random-effects meta-analyses used standardized mean differences (SMDs) for pain intensity and odds ratios for rescue medication use. Adverse events were summarized narratively. Four RCTs (n = 825) were included: three placebo-controlled trials and one route-comparison trial, all evaluating short-term treatment for acute pain with subcutaneous diclofenac or ketorolac. In the meta-analysis of three placebo-controlled trials (n = 500), subcutaneous NSAIDs reduced pain (SMD = 0.72; 95% CI, 0.22 to 1.21; I2 = 82.8%) and rescue medication use. Adverse-event data were limited and inconsistent, with one trial reporting higher event rates with subcutaneous NSAIDs than placebo and another reporting comparable rates. The route-comparison trial showed comparable efficacy and safety between subcutaneous and intramuscular diclofenac. In conclusion, subcutaneous diclofenac and ketorolac may reduce short-term acute pain compared with placebo. However, the evidence is limited and safety remains uncertain. Further route-comparison studies are needed.