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

last 15 years (since January 1st, 2003) as this period was considered clinically relevant. Clinical recommendations were based on the American College of Physicians (ACP) guidelines.10 We excluded studies using proprietary or undescribed active ingredients (as these studies and outcomes would not be verifiable or reproducible by third parties, if desired) and those evaluating non-topical agents (ie, oral medications, bleaching agents, chemical peels, intralesionally administered drugs, laser, and light-based therapies) as stand-alone or combination approaches. Patients were allowed to apply daily sunscreen in the included studies. Non-randomized original reports, literature reviews, conference abstracts, oral presentations, basic science investigations, animal studies, and non-English articles were excluded. We examined the bibliographies of included published original reports and literature reviews to ensure that relevant articles were included in the systematic search.


Our systematic search identified 9,413 articles. After screening titles, abstracts, and full text articles, we identified 35 original RCTs using azelaic acid (2), cysteamine (2), epidermal growth factor (EGF) (1), liposomal hydroquinone (1), lignin peroxidase (1), mulberry extract (1), niacinamide (1), Rumex occidentalis (1), tranexamic acid (TXA) (5), TC therapy (5), 4-n-butylresorcinol (3), glycolic acid (2), kojic acid (2), aloe vera (1), ascorbic acid (1), dioic acid (1), ellagic acid and arbutin (1), flutamide (1), parsley (1), or zinc sulfate (2) for melasma. Table 1 provides a detailed summary of the identified studies and highlights study designs, treatment parameters, results, and adverse events (AEs).