Efficacy and safety of over-the-counter analgesics for primary dysmenorrhea: A network meta-analysis

BACKGROUND: Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs – naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen – in patients with primary dysmenorrhea. METHODS: The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. RESULTS: Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18–7.30), ibuprofen (OR 10.08, 95% CI 3.29–30.85), diclofenac (OR 11.82, 95% CI 2.66–52.48), and ketoprofen (OR 5.12, 95% CI 1.57–16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04–0.73) and diclofenac (OR 1.17, 95% CI 0.02–0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18–15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04–0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18–0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac. CONCLUSION: Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.