An Updated Review of Melasma Treatments

Woman with melasma and magnifying glass
A multimodality approach to treating melasma may be the most successful.
An international team of researchers summarizes the available medical therapies for melasma and offers suggestions and recommendations for the use of these therapies in clinical practice.

A review from an international team of researchers summarizes the available medical therapies for melasma and offers suggestions and recommendations for the use of these therapies in clinical practice. The review was published online in the Journal of Cosmetic Dermatology.1

Medical Therapies for Melasma

In their paper, the researchers wrote that medical therapies are the preferred first-line approaches for treating, maintaining remission, and preventing recurrences of melasma. The researchers added that nonmedical approaches such as dermabrasion, chemical peels, and lasers (Erbium:YAG laser, Q-switched Nd-YAG laser, Q-switched ruby, pulsed dye laser, fractional lasers), intense pulsed light (IPL), and radiofrequency microneedling also feature utility in the management of “treatment-resistant or difficult-to-treat cases despite the risk of rebound hyperpigmentation, acneiform eruptions, physical urticaria, petechiae, [and] reactivation of herpes simplex infection.”

Below is a summary of the therapies and strategies used to treat and camouflage melasma, according to the researchers:

  • Hydroquinone (HQ) and HQ Derivatives: The researchers wrote that the hydroxyphenolic compound hydroquinone is extensively used as monotherapy or in combination with other agents for topical melasma treatment. The agent inhibits DOPA conversion to melanin via inhibition of tyrosinase activity “possibly interacting with copper at the active end of the enzyme,” the researchers wrote. A concern with hydroquinone, the researchers added, is the compound’s “propensity for rapid oxidation resulting in unstable formulations, discoloration, decreased efficacy, and actual depigmentation from melanotoxic hydroxybenzoquinone and p-benzoquinone, the byproducts of its oxidation.”
  • Corticosteroids: According to the researchers, corticosteroids feature a short-lived effect on melasma, and treatment with these agents alone is rarely used given their risk for cutaneous adverse effects. However, the researchers suggest that corticosteroids dexamethasone, fluocinolone acetonide, fluticasone, hydrocortisone, and mometasone furoate are preferred for triple combination treatment of melasma.
  • Retinoids: Tretinoin is a frequently used and effective retinoid in the treatment of melasma, yet the researchers noted that this therapy requires 24 weeks or longer before clinical improvements become apparent. The researchers noted that tretinoin inhibits tyrosinase transcription and related proteins 1 and 2, the former of which interrupts melanin synthesis following exposure to ultraviolet (UV) B. In addition, the product reduces melanosome transfer and can improve “penetration of other active ingredients like hydroquinone” when used in combination therapy. Although effective for the treatment of melasma, the researchers noted that most patients can experience burning, erythema, itching, and scaling with continuous therapy but added that adapalene is “well tolerated and equally effective among retinoids in long-term melasma treatment.”
  • Azelaic Acid (AA): The dicarboxylic acid AA features antiproliferative as well as selective cytotoxic effects on abnormally hyperactive melanocytes via inhibition on tyrosinase and mitochondrial oxidoreductase enzymes. According to the researchers, there are minimal effects of AA on normally pigmented skin. They cited studies which showed that AA monotherapy at concentrations 15% to 20% is effective for melasma and postinflammatory hyperpigmentation and equally effective as hydroquinone 4%.
  • Kojic Acid (KA): According to the researchers, KA inhibits free tyrosinase and features antioxidant effects. The researchers cited studies that demonstrate the benefit of KA in melasma when used in combination with hydroquinone 2%, in addition to combination with glycolic acid 10% and hydroquinone 2%. Although  the researchers noted that KA could be a useful option in patients who have a suboptimal response to hydroquinone and glycolic acid or those who are intolerant to first-line treatments, KA is a potential irritant and contact sensitizer and may cause pigmented contact dermatitis.
  • Arbutin: A derivative of hydroquinone, arbutin “competitively inhibits enzyme tyrosinase and 5,6-dihydroxyindole-2- carboxylic acid polymerase activity in vitro in a dose-dependent manner,” the researchers wrote. They added that in vitro research suggests arbutin’s inhibitory effect on tyrosinase activity is equivalent to that of hydroquinone but noted that there is a lack of “good clinical studies” on the safety and efficacy of arbutin in patients with melasma.
  • Tranexamic Acid (TA): Topical and oral TA have demonstrated efficacy for the treatment of melasma in some studies, with clinical effect occurring between 2 to 3 months of use, according to the researchers. In terms of the TA’s mechanism of action, the researchers indicate that the acid reduces epidermal pigmentation and erythema of melasma, possibly via inhibition of plasmin or decreased UV-induced plasmin activity in keratinocytes and ultimately reductions in tyrosinase activity in melanocytes.

Cosmeceuticals and Botanicals

In addition to medical therapies, the researchers also provided a summary of naturally occurring depigmenting ingredients and agents that have been studied in the treatment of melasma:

  • Ascorbic acid: Vitamin C, which is commonly used in skin-whitening products, reduces dopaquinone to DOPA, acts as an antioxidant, and provides a photoprotective effect on the skin. The researchers noted that ascorbic acid inhibits melanogenesis via inhibition of tyrosinase activity via copper interaction. Additionally, the researchers cited studies that suggest ascorbic acid in magnesium ascorbyl-2-phosphate (MAP) cream form is more effective than vitamin C in its natural form but added that the other esterified forms such as ascorbyl- 6-palmitate and tetrahexyldecyl ascorbate are also more stable than the natural form of vitamin C.
  • Vitamin E: While also serving as an antioxidant, the researchers wrote that vitamin E offers photoprotection and can lead to depigmentation by inhibiting tyrosinase, increasing intracellular glutathione content, and interfering with lipid peroxidation of melanocyte membranes. The researchers added that studies have demonstrated that a combination of topical vitamins E and C appears to result in significantly greater improvements in melasma and pigmented contact dermatitis compared with the use of either vitamin alone.
  • Topical rucinol: According to the researchers, the phenolic derivative rucinol inhibits ty- rosinase and tyrosinase-related protein (TRP-1), supporting the rationale for its use in melasma. The researchers cited studies that have previously demonstrated significant melasma improvements with the use of twice daily topical rucinol in women.
  • Cysteamine: The natural aminothiol biological compound cysteamine is part of the vitamin B3 family, and according to the researchers, has antioxidant capabilities and inhibits melanosomal transfer. Available as cysteamine + isobionic-amide complex 5% topical cream, cysteamine has demonstrated favorable safety with “very low risk of adverse effects,” the researchers wrote. 
  • Sunscreens and makeup: Given that UV radiation and visible light play a role in melasma pathogenesis, the researchers indicated that all patients with melasma should be prescribed sunscreens of SPF 15 or higher. The researchers added that physical sunscreens that contain zinc oxide and titanium dioxide, iron oxides, and silicones are photoprotective and provide a white camouflage effect, which may be preferred for patients with melasma. While sunscreen takes time to provide a difference in skin tone, the researchers noted that cosmetic camouflage can provide more immediate visible effects and can be encouraged. 

Treatment Algorithm

The researchers suggested a treatment algorithm (Figure 1) that could be used as “a quick reference guide in routine office practice” for the treatment of melasma. The algorithm involves several evidence-based treatment approaches for mild and moderate/severe melasma.

Figure 1. Melasma Treatment Algorithm1

Abbreviations: AA, Azelaic acid; HQ, hydroquinone; IPL, Intense pulse light; KA, Kojic acid; NAFL, Nonablative fractional laser; PDL, Pulsed dye laser; QSNY, Q-switched Nd:YAG laser; TXA, tranexamic acid.

“Nevertheless, a multimodality approach such as using a topical formulation, sunscreen, oral TA, and Polypodium leucotomos in combination or in a sequential manner with IPL and/or PDL to treat the vascular component then a low fluence 1927 nm laser will perhaps provide an effective treatment approach,” the researchers wrote.


Mahajan VK, Patil A, Blicharz L, et al. Medical therapies for melasma. J Cosmet Dermatol. Published online July 19, 2022. doi:10.1111/jocd.15242