Efficacy and Safety of Different Treatments for Melasma: Network Meta-Analysis of Updated Data

Background: Melasma is a chronic, relapsing pigmented skin disease with challenging and unsatisfactory treatment outcomes. This study aims to compare the efficacy and safety of different treatments for melasma. Methods: We conducted a comprehensive search of PubMed and EMBASE databases to identify randomized controlled clinical trials (RCTs) for melasma treatment modalities between January 2022 and January 2025. Relative efficacy refers to the comparison of the improvement in melasma severity before and after treatment for all modalities of interest at a specific time point. The Melasma Area Severity Index (MASI) (also known as modified MASI (mMASI) or half-MASI score) was defined as the efficacy index. Safety refers to the incidence of the most common adverse events. The quality of the included trials was assessed using the GRADE method. Results: The analysis included 14 clinical trials with 15 treatment modalities involving 738 women who met the inclusion criteria. The mean difference in efficacy index showed that intradermal PRP (platelet-rich plasma) and intradermal PRP + oTXA (oral tranexamic acid) were the best treatment options compared with HQ4%, intradermal TXA, intradermal PRGF (plasma rich in growth factor) + HQ4 (hydroquinone 4%), followed by intradermal TXALaser (intradermal TXA + Q-switched fractional 1064-nmNd:YAG lasers). The efficacy indices of other modalities were comparable. Most treatment-related adverse events were mild, were well tolerated, or resolved with treatment. The quality of evidence was generally high. Conclusions: This NMA showed that intradermal PRP in combination or alone is an effective and safe treatment option for melasma. PRP may be a direction for the development of new melasma treatment options in the future, but well-designed, comprehensive, large-scale randomized controlled trials are needed to verify it.