Topical Treatments for Melasma: A Systematic Review of Randomized Controlled Trials

November 2019 | Volume 18 | Issue 11 | Original Article | 1156 | Copyright © November 2019

Evan Austin BS,ª Julie K. Nguyen MD,a,b Jared Jagdeo MD MSa,b

ªDepartment of Dermatology, State University of New York, Downstate Medical Center, Brooklyn, NY 

BDermatology Service, VA New York Harbor Healthcare System Brooklyn Campus, Brooklyn, NY


We performed a systematic review of topical treatments for melasma. Strong evidence-based recommendations include cysteamine, TC, and TXA as first-line treatments for melasma. Cysteamine has excellent efficacy, is reported to have anti-cancer properties, and has no known risk for thrombosis or ochronosis. TC therapies and TXA are effective for melasma but carry theoretical risks for ochronosis or thrombosis, respectively. Natural compounds are associated with low risk for AEs, but more research is needed to determine the efficacy, optimal formulation, and appropriate concentration of novel treatments.

For all topical agents, continued treatment and use of medications is necessary as pigmentation may recur following treatment cessation. Future large RCTs with control arms using standard-of-care treatments (ie, HQ or TC) are necessary to assess the relative risks and benefits of a novel agent. Current topical treatments mostly inhibit melanin formation and transfer, but do not target the vascular components of melasma, inflammation, or underlying disease etiology. We believe that synergetic combination approaches are likely to have greater efficacy than stand-alone treatments. Future mechanistic research on the underlying etiology of melasma may facilitate the development of targeted approaches.


Dr. Jagdeo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Acquisition, analysis, and interpretation of data: EA and JN. Drafting of the manuscript: EA. Critical revision of the manuscript for important intellectual content: JN and JJ.


Dr. Jagdeo is a speaker for L’Oréal/Skinceuticals and a consultant for Scientis. Dr. Jagdeo is on the scientific advisory board for Sun Pharma/DUSA Pharmaceuticals, Inc. for the product Levulan® photodynamic therapy. No funding has been received for this article. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the U.S. Department of Veterans Affairs or the United States Government.



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