Purpose This article attempted to describe the efficacy and safety of 1064QNYL in combination with other treatments for refractory melasma. Methods Two researchers independently retrieved randomized controlled trials (RCTs) according to inclusion and exclusion criteria. Primary outcome was evaluated with MASI and mMASI scores in control group and experiment group. The secondary outcome was evaluated with MI scores. We calculated 95% CI of standardized mean difference (SMD) and heterogeneity of the included literature by Higgins I2 test, and assessed publication bias by Funnel plots, Egger's, and Begg's tests. Results A total of 12 articles including 322 subjects were analyzed. Experiment group was treated with 1064QNYL combined with single treatment (e.g., PDL, IPL, RF, and TA). Control group was treated with 1064QNYL alone. A greater reduction of Melasma Area and Severity Index (MASI)/modified Melasma Area and Severity Index (mMASI) scores were shown in experiment group than that in control group at the end of the treatment (SMD, −0.37; 95% CI −0.70 to −0.04, p = 0.03, I2 = 33%). The SMD of MI scores further supported this conclusion by −0.32 (95% CI −0.63 to −0.02, p = 0.04, I2 = 27%). As for adverse events (AEs), combined treatment gave rise to more mild burning, stinging, and erythema that resolved spontaneously. Several studies reported focal purpura, punctate leukoderma, hyperpigmentation, hypopigmentation, and so on. Conclusion Combined 1064QNYL treatment was better than single laser treatment, with the highest short‐term benefit and long‐term follow‐up to maintain the effect in favor of combined treatment.
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