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

Abstract

Background: Melasma is an acquired skin disease characterized by symmetric hyperpigmentation on sun-exposed areas, particularly on the face. Recently, there has been tremendous scientific interest in novel, safe, and effective topical agents to manage melasma.

Objective: To evaluate topical treatments for melasma and provide evidence-based recommendations for clinical use and further research.

Methods: We performed a systematic review of randomized controlled trials (RCTs) on topical agents for the treatment of melasma on March 4th, 2019 using PRISMA guidelines. Clinical recommendations were based on the American College of Physicians guidelines. 

Results: After screening, we identified 35 original RCTs using azelaic acid, cysteamine, epidermal growth factor, hydroquinone (liposomal-delivered), lignin peroxidase, mulberry extract, niacinamide, Rumex occidentalis, triple combination therapy, tranexamic acid, 4-n-butylresorcinol, glycolic acid, kojic acid, aloe vera, ascorbic acid, dioic acid, ellagic acid and arbutin, flutamide, parsley, or zinc sulfate for melasma.

Conclusions: Cysteamine, triple combination therapy, and tranexamic acid received strong clinical recommendations for the treatment of melasma. Cysteamine has excellent efficacy and is reported to have anti-cancer properties, but has not been directly compared with hydroquinone. Triple combination agents and tranexamic acid are effective, but carry theoretical risks for ochronosis and thrombosis, respectively. Natural compounds are associated with low risk for adverse events, but more research is needed to determine the efficacy, optimal formulation, and appropriate concentration of novel treatments. 

J Drugs Dermatol. 2019;18(11):1156-1171. 

INTRODUCTION

Melasma is an acquired skin disease characterized by symmetric patches of hyperpigmentation on sun-exposed areas such as the cheeks, forehead, chin, nose, and upper lips. Histological features may include epidermal and dermal pigmentation, solar elastosis, increased vascularization, and mastocytosis.1

Although the true incidence of melasma is unknown, melasma has been reported to affect 1% to 50% of the population globally.2 Melasma is more prevalent in female patients of Asian, Latin American, Middle Eastern, and African descent due to multifactorial causes including increased skin pigmentation, alterations in hormone levels, family history, and sun exposure.3-6 Melasma has a tremendous societal and psychosocial impact as patients with melasma report dramatically lower self-esteem, depression, and social isolation.7,8

Therapy for melasma remains a clinical challenge and topical agents are the mainstay. First-line topical treatment options for melasma are hydroquinone (HQ) and triple combination (TC) therapies, which include HQ, a retinoid, and a steroid. Second-line treatments include chemical peels and laser therapies.9 There have been concerns about the long-term safety and efficacy of HQ. Topical HQ is associated with ochronosis, a bluish-gray discoloration of the skin.9 In response, HQ has been banned in the European Union as a cosmetic additive, but is available as a prescription medication.9

Recently, there has been tremendous scientific and general public interest in novel, safe, and effective topical agents to improve melasma. To determine the safety and efficacy of newer topical agents for melasma, we performed a systematic review of randomized controlled trials (RCTs) on topical agents for the treatment of melasma and provided evidence-based recommendations for clinical use and further research.

METHODS

According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol, we performed a systematic search for novel and currently used topical treatments for melasma on March 4th, 2019 (Figure 1). Included articles were RCTs using topical treatments for melasma published within the