Efficacy and Safety of Hyaluronic Acid Fillers With or Without Lidocaine in the Treatment of Nasolabial Folds: An Updated Systematic Review and Meta-Analysis.

objectiveTo update the evidence on the effectiveness and safety of hyaluronic acid gel combined with lidocaine for treating nasolabial folds.

methodsWe searched electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science using subject headings and keywords associated with hyaluronic acid and lidocaine in the context of nasolabial folds. Inclusion criteria were met by randomized controlled trials (RCTs) comparing the efficacy and safety of hyaluronic acid gel with or without lidocaine. Outcomes measured included visual pain analog scale (VAS) scores, wrinkle severity scale scores, and adverse events. The quality of RCTs was evaluated using the Cochrane Randomized Controlled Trials Scale, which encompasses criteria such as randomization, allocation concealment, blinding, dropout, and withdrawal rates, and was assessed by two independent reviewers.

resultsNo significant difference in overall wrinkle severity rating scale scores was observed between HA with lidocaine and HA without lidocaine [MD = 0.08, 95% CI (- 0.09, 0.24), P = 0.36]. However, there was a significant reduction in pain scale scores (VAS) [SMD = -2.47, 95% CI (- 4.15, - 0.79), P = 0.004]; no significant differences were noted in the ncidence of at least one adverse event [RR = 0.97, 95% CI (0.90, 1.05), P = 0.51]; and there were no significant differences in swelling [RR =  0.99, 95% CI (0.92, 1.06), P = 0.80], erythema [RR = 1.01, 95% CI (0.91, 1.11), P = 0.91], bruising [RR = 0.99, 95% CI (0.89, 1.13), P = 0.86], itching [RR = 1.03, the 95% CI (0.88, 1.21), P = 0.74], induration [RR = 1.04, 95% CI (0.92, 1.17), P = 0.55], and papules [RR = 0.77, 95% CI (0.58, 1.02), P = 0.07]. There was a significantly lower incidence of tenderness [RR = 0.91, 95% CI (0.86, 0.97), P = 0.002] only in the control group. Sensitivity analysis confirmed the stability of results across all outcome indicators with low sensitivity and high confidence. Subgroup analysis indicated higher wrinkle severity scores among East Asians compared to Europeans and Americans.

conclusionsHA containing lidocaine significantly reduces pain and is comparable in effectiveness and safety of HA without lidocaine. The clinical effects appear more pronounced in East Asians. Due to the limited number of related studies, further research is necessary. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .