Management of pain with oral analgesia after extraction of lower third molars: a network meta-analysis of randomized controlled trials

The aim of this network meta-analysis was to compare and rank single-dose oral analgesics for managing moderate-to-severe pain after third molar surgery, to address limitations of prior reviews. Major databases were searched for relevant randomized controlled trials (RCTs), and guidelines for reporting systematic reviews were followed. The primary outcome was total pain relief over 6 h, with data standardized for comparability. A frequentist network meta-analysis was performed to estimate mean differences and rank treatment strategies. The certainty of the evidence was formally graded. Nineteen randomized controlled trials involving 3615 third molar surgeries were included in the network meta-analysis. All active drug classes outperformed placebo. The combination of an opioid with a non-steroidal anti-inflammatory drug (NSAID) ranked as the most effective strategy, followed by NSAIDs alone. Additionally, the combination of opioids with non-opioid analgesics showed superior efficacy compared to either as monotherapy in pairwise comparisons, although this was not fully reflected in the overall treatment ranking, where it did not outperform non-opioid analgesics. Significant inconsistency was found across the evidence network, and certainty for most comparisons was very low to moderate. Consequently, given the high heterogeneity across studies, treatment effects may vary, warranting careful consideration in clinical practice.