Melasma Treatment: An Evidence-Based Review
Melasma is an acquired, chronic pigmentary disorder predominantly affecting women. It may significantly affect quality of life and self-esteem due to its disfiguring appearance. Multiple treatments for melasma are available, with mixed results.
The aim of this article was to conduct an evidence-based review of all available interventions for melasma.
A systematic literature search of the PubMed electronic database was performed using the keywords ‘melasma’ and/or ‘chloasma’ in the title, through October 2018. The search was then limited to ‘randomized controlled trial’ and ‘controlled clinical trial’ in English-language journals. The Cochrane database was also searched for systematic reviews.
The electronic search yielded a total of 212 citations. Overall, 113 studies met the inclusion criteria and were included in this review, with a total of 6897 participants. Interventions included topical agents, chemical peels, laser- and light-based devices, and oral agents. Triple combination cream (hydroquinone, tretinoin, and corticosteroid) remains the most effective treatment for melasma, as well as hydroquinone alone. Chemical peels and laser- and light-based devices have mixed results. Oral tranexamic acid is a promising new treatment for moderate and severe recurrent melasma. Adverse events from all treatments tend to be mild, and mainly consist of skin irritation, dryness, burning, erythema, and post-inflammatory hyperpigmentation.
Hydroquinone monotherapy and triple combination cream are the most effective and well-studied treatments for melasma, whereas chemical peels and laser- and light-based therapies are equal or inferior to topicals, but offer a higher risk of adverse effects. Oral tranexamic acid may be a safe, systemic adjunctive treatment for melasma, but more studies are needed to determine its long-term safety and efficacy. Limitations of the current evidence are heterogeneity of study design, small sample size, and lack of long-term follow-up, highlighting the need for larger, more rigorous studies in the treatment of this recalcitrant disorder.
The authors are responsible for the accuracy of the information presented.
Compliance with Ethical Standards
This article has no funding source.
Conflict of interest
Jacqueline-McKesey, Andrea Tovar-Garza and Amit G. Pandya have no conflicts of interest to disclose.
- 7.Ponzio HA, Favaretto AL, Rivitti EA. Proposal of a quantitative method to describe melasma distribution in women. J Cosmet Dermatol. 2007;20:103–11.Google Scholar
- 8.Rajaratnam R, Halpern J, Salim A, Emmett C. Interventions for melasma. Cochrane Database Syst Rev. 2010;7(7):CD003583.Google Scholar
- 15.Sivayathorn A, Verallo-Rowell V, Graupe K. 20% azelaic acid cream in the topical treatment of melasma: a double-blind comparison with 2% hydroquinone. Eur J Dermatol. 1995;5:680–4.Google Scholar
- 40.Tehranchinia Z, Saghi B, Rahimi H. Evaluation of therapeutic efficacy and safety of tranexamic acid local infiltration in combination with topical 4% hydroquinone cream compared to topical 4% hydroquinone cream alone in patients with melasma: a split-face study. Dermatol Res Pract. 2018;2018:8350317.PubMedPubMedCentralCrossRefGoogle Scholar
- 41.Steiner D, Feola C, Bialeski N, Ayeres de Morais e Silva F, César Pessanha Antiori A, Alvim Sant’Anna Addor F, Brandão Folino B. Study evaluating the efficacy of topical and injected tranexamic acid in treatment of melasma. Surg Cosmet Dermatol. 2009;1(4):174–7.Google Scholar
- 42.Budamakuntla L, Loganathan E, Suresh DH, Shanmugam S, Suryanarayan S, Dongare A, Venkataramiah LD, Prabhu N. A randomised, open-label, comparative study of tranexamic acid microinjections and tranexamic acid with microneedling in patients with Melasma. J Cutan Aesthet Surg. 2013;6(3):139–43.PubMedPubMedCentralCrossRefGoogle Scholar
- 44.Torok H, Taylor S, Baumann L, Jones T, Wieder J, Lowe N, Jarret M, Rich P, Pariser D, Tschen E, Martin D, Menter A, Weiss J. A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads. J Drugs Dermatol. 2005;4(5):592–7.PubMedGoogle Scholar
- 46.Chan R, Park KC, Lee MH, Lee ES, Chang SE, Leow YH, Tay YK, Legarda-Montinola F, Tsai RY, Tsai TH, Shek S, Kerrouche N, Thomas G, Verallo-Rowell V. A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008;159(3):697–703.PubMedGoogle Scholar
- 47.Gong Z, Lai W, Zhao G, Wang X, Zheng M, Li L, Yang Q, Dang Y, Liu L, Zou Y. Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream in Chinese patients with melasma: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Clin Drug Investig. 2015;35(6):385–95.PubMedCrossRefGoogle Scholar
- 48.Arellano I, Cestari T, Ocampo-Candiani J, Azulay-Abulafia L, Bezerra Trindade Neto P, Hexsel D, Machado-Pinto J, Muñoz H, Rivitti-Machado MC, Sittart JA, Trindade de Almeida AR, Rego V, Paliargues F, Marques-Hassun K. Preventing melasma recurrence: prescribing a maintenance regimen with an effective triple combination cream based on long-standing clinical severity. J Eur Acad Dermatol Venereol. 2012;26(5):611–8.PubMedCrossRefGoogle Scholar
- 53.Francisco-Diaz J, Cristi-Cataluna I, Cruz DD, Verallo-Rowell VM. A double-blind randomized placebo-controlled trial on the efficacy and safety of botanical extract (Gigawhite_ 5% solution) in the treatment of melasma. J Philos Dermatol Soc. 2004;13:18–23.Google Scholar
- 58.Pratchyapurit WO. Combined use of two formulations containing diacetyl boldine, TGF-β1 biomimetic oligopeptide-68 with other hypopigmenting/exfoliating agents and sunscreen provides effective and convenient treatment for facial melasma. Either is equal to or is better than 4% hydroquinone on normal skin. J Cosmet Dermatol. 2016;15(2):131–44.PubMedCrossRefGoogle Scholar
- 61.Morag M, Nawrot J, Siatkowski I, Adamski Z, Fedorowicz T, Dawid-Pac R, Urbanska M, Nowak G. A double-blind, placebo-controlled randomized trial of Serratulae quinquefoliae folium, a new source of β-arbutin, in selected skin hyperpigmentation. J Cosmet Dermatol. 2015;14(3):185–90.PubMedCrossRefGoogle Scholar
- 71.Adalatkhah H, Sadeghi-Bazargani H. The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: a randomized clinical trial. Drug Des Dev Ther. 2015;9:4219–25.Google Scholar
- 82.Ejaz A, Raza N, Iftikhar N, Muzzafar F. Comparison of 30% salicylic acid with Jessner’s solution for superficial chemical peeling in epidermal melasma. J Coll Phys Surg Pak. 2008;18(4):205–8.Google Scholar
- 86.Murtaza F, Bangash AR, Khushdil A, Noor SM. Efficacy of trichloro-acetic acid peel alone versus combined topical magnesium ascorbyl phosphate for epidermal melasma. J Coll Phys Surg Pak. 2016;26(7):557–61.Google Scholar
- 89.Goldman MP, Gold MH, Palm MD, Colon LE, Preston N, Johnson LA, Gottschalk RW. Sequential treatment with triple combination cream and intense pulsed light is more efficacious than sequential treatment with an inactive (control) cream and intense pulsed light in patients with moderate to severe melasma. Dermatol Surg. 2011;37(2):224–33.PubMedCrossRefGoogle Scholar
- 91.Chung JY, Lee JH, Lee JH. Topical tranexamic acid as an adjuvant treatment in melasma: side-by-side comparison clinical study. J Dermatol Ther. 2016;27(4):373–7.Google Scholar
- 94.Yun WJ, Lee SM, Han JS, Lee SH, Chang SY, Haw S, Lee JB, Won CH, Lee MW, Choi JH, Chang SE. A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians. J Cosmet Laser Ther. 2015;17(5):259–66.PubMedCrossRefGoogle Scholar
- 95.Park KY, Kim DH, Kim HK, Li K, Seo SJ, Hong CK. A randomized, observer-blinded, comparison of combined 1064-nm Q-switched neodymium-doped yttrium–aluminum–garnet laser plus 30% glycolic acid peel vs. laser monotherapy to treat melasma. J Clin Exp Dermatol Res. 2011;36(8):864–70.CrossRefGoogle Scholar
- 97.Ustuner P, Balevi A, Ozdemir M. A split-face, investigator-blinded comparative study on the efficacy and safety of Q-switched Nd:YAG laser plus microneedling with vitamin C versus Q-switched Nd: YAG laser for the treatment of recalcitrant melasma. J Cosmet Laser Ther. 2017;19(7):383–90.PubMedCrossRefGoogle Scholar
- 98.Kaminaka C, Furukawa F, Yamamoto Y. The clinical and histological effect of a low-fluence Q-Switched 1,064-nm neodymium:yttrium-aluminum-garnet laser for the treatment of melasma and solar lentigines in asians prospective, randomized, and split-face comparative study. Dermatol Surg. 2017;43(9):1120–33.PubMedCrossRefGoogle Scholar
- 108.Wind BS, Kroon MW, Meesters AA, Beek JF, van der Veen JW, Nieuweboer-Krobotová L, Bos JD, Wolkerstorfer A. Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled split-face study. Lasers Surg Med. 2010;42(7):607–12.PubMedCrossRefGoogle Scholar
- 109.Kroon MW, Wind BS, Beek JF, Van Der Veen JW, Nieuweboer-Krobotová L, Bos JD, Wolkerstorfer A. Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled pilot study. J Am Acad Dermatol. 2011;64(3):516–23.PubMedCrossRefGoogle Scholar
- 115.Choi YJ, Nam JH, Kim JY, Min JH, Park KY, Ko EJ, Kim BJ, Kim WS. Efficacy and safety of a novel picosecond laser using combination of 1 064 and 595 nm on patients with melasma: a prospective, randomized, multicenter, split-face, 2% hydroquinone cream-controlled clinical trial. Lasers Surg Med. 2017;49(10):899–907.PubMedCrossRefGoogle Scholar
- 118.Sadako N. Treatment of melasma with tranexamic acid. Clin Rep. 1979;13:3129–31.Google Scholar
- 120.Higashi N. Treatment of melasma with oral tranexamic acid. Skin Res. 1988;30:676–80.Google Scholar
- 121.Zhu HJ, Yang XH. The clinical study of acidum tranexamicum on melasma. Pharm Prog. 2001;3:178–81.Google Scholar
- 125.Lajevardi V, Ghayoumi A, Abedini R, Hosseini H, Goodarzi A, Akbari Z, Hedayat K. Comparison of the therapeutic efficacy and safety of combined oral tranexamic acid and topical hydroquinone 4% treatment vs. topical hydroquinone 4% alone in melasma: a parallel-group, assessor- and analyst-blinded, randomized controlled trial with a short-term follow-up. J Cosmet Dermatol. 2017;16(2):235–42.PubMedCrossRefGoogle Scholar
- 135.Martin LK, Caperton C, Woolery-Lloyd H, et al. A randomized double-blind placebo-controlled study evaluating the effectiveness and tolerability of oral Polypodium leucotomos in patients with melasma. American Academy of Dermatology Annual Meeting: 16–20 March 2012; San Diego.Google Scholar
- 139.Teo WL, Gan E, Jinghan A, Chuah SY, Alain K, et al. Double blind placebo controlled trial to evaluate of the effectiveness of a dietary supplement rich in carotenoids as adjunct to topical lightening cream for the treatment of melasma: a pilot study. Pigment Disord. 2015;2(2):164.Google Scholar
- 141.Hamadi SA, Mohammed MM, Aljaf AN, Abdulrazak A. The role of topical and oral melatonin in management of melasma patients. J Arab Univ Basic Appl Sci. 2009;8:30–42.Google Scholar