The effect of pregabalin for pain after third molar surgery: a systematic review and meta-analysis

Pregabalin has been proposed as an adjunct for postoperative pain management following third molar surgery, but its analgesic efficacy, safety, and clinical applicability remain uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) ascertaining pregabalin for pain after third molar extraction.

A systematic search was conducted across PubMed, Scopus, Web of Science, and Google Scholar up to January 2025. RCTs appraising pregabalin for postoperative pain following third molar surgery were included. The primary outcome was pain intensity (VAS) and the secondary outcome was adverse events (AEs). Data were pooled using a random-effects meta-analysis, with mean difference (MD) for pain scores and odds ratio (OR) for AEs, each with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2 tool.

Six RCTs involving 545 patients undergoing third molar surgery were included. Of these, 170 patients (4 RCTs) contributed data to the quantitative synthesis. Pregabalin significantly mitigated postoperative pain compared with control (MD − 0.99, 95% CI − 1.46 to − 0.52, p < 0.00001), though substantial heterogeneity was observed (I²=91%). Subgroup analysis by timepoint revealed consistent but individually nonsignificant reductions in pain at 2–24 h postoperatively. Pregabalin use was linked to a higher risk of adverse events (OR 4.36, 95% CI 2.52–7.55, p < 0.00001, I²=77%), with a dose–response effect observed (ORs: 1.18 for 50 mg, 5.19 for 75 mg, 11.16 for 300 mg). Risk of bias was high or raised some concerns in three of the six included trials, with the certainty of evidence being limited by the substantial heterogeneity.

Pregabalin may provide a modest reduction in postoperative pain following third molar surgery; however, the clinical relevance and robustness of this benefit remain uncertain due to substantial heterogeneity and sensitivity to a single study. In contrast, pregabalin was consistently associated with an increased risk of adverse events. Therefore, the benefit–harm balance does not clearly support routine use of pregabalin as a first-line analgesic in this setting. Further high-quality, placebo-controlled RCTs with standardized dosing, comparator groups, and postoperative assessment timepoints are needed.