Self-applied Topical Interventions for Melasma

A Systematic Review and Meta-analysis of Data From Randomized, Investigator-blinded Clinical Trials

Antonia Pennitz; Maria Kinberger; Gabriela Avila Valle; Thierry Passeron; Alexander Nast; Ricardo N. Werner


The British Journal of Dermatology. 2022;187(3):309-317. 

In This Article

Abstract and Introduction


Background: Melasma is a common dermatological condition. Although its relevance as a skin condition is primarily of a cosmetic nature, it may affect the patient's wellbeing and quality of life. A broad range of treatment options is available, which makes it difficult to choose the most appropriate of those treatments.

Objectives: To summarize and critically appraise evidence from investigator-blinded randomized controlled trials (RCTs) on the efficacy and safety of self-applied topical interventions for melasma.

Methods: We systematically searched MEDLINE and the Cochrane CENTRAL trials database for RCTs on topical, self-administered interventions for patients diagnosed with melasma. Eligibility was limited to RCTs that explicitly stated in their methods section (i) how they generated the random allocation sequence, and (ii) that the study outcome assessor was blinded to the participants' group allocation. Outcomes of interest included evaluator-assessed clinical scores (such as the Melasma Area and Severity Index), quality of life and patient-reported outcomes, as well as safety outcomes. The study findings were meta-analysed, pooling data from studies on the same comparisons, if this was possible. We assessed confidence in effect estimates using the GRADE approach.

Results: Our searches yielded 1078 hits. We included 36 studies reporting on 47 different comparisons of interventions. These included medical treatments such as 'triple combination cream' (TCC), over-the-counter cosmetic and herbal products, as well as sun creams covering different light spectra. Pooling data was possible for only two comparisons, topical tranexamic acid (TXA) vs. hydroquinone (HQ) and cysteamine vs. placebo. Direct comparisons were available for a variety of interventions; however, the reported outcomes varied greatly. Overall, our confidence in the effect estimates ranged from very low to high.

Conclusions: Our findings indicate that TCC and its individual components HQ and tretinoin are effective in lightening melasma. Besides these established self-applied treatment options, we identified further medical treatments as well as promising cosmetic and herbal product treatment approaches. Furthermore, evidence suggests that using broad-spectrum sunscreen covering both the visible and ultraviolet-light spectrum enhances the treatment efficacy of HQ. However, with mostly small RCTs comparing treatments directly using a broad range of outcomes, further research is needed to draw conclusions about which treatment is most effective.


Melasma is a common skin condition characterized by an acquired symmetrical cutaneous hypermelanosis.[1,2] Its pathogenesis is complex, involving not only melanocytes, but also keratinocytes, fibroblasts and endothelial cells along with an altered basement membrane.[3–5] Several known risk factors include exposure to ultraviolet (UV)[6,7] and visible light,[8–11] genetic predisposition,[12,13] oral contraceptives,[14,15] pregnancy[16,17] and female sex.[5,18] Melasma is most common in Asian and Latin women of reproductive age[19–22] with Fitzpatrick skin types II–IV.[23,24] Its prevalence varies widely among countries[2,20] according to the distribution of different ethnicities[20–22] and skin phototypes.[23,24]

Because it occurs most commonly on the central face, forehead, temple and cheeks, melasma can severely affect emotional wellbeing, self-esteem and overall quality of life.[25–28] Treatments include a broad range of medical and cosmetic interventions, albeit characterized by inconsistent results and frequent relapses.[29–31]

This paper aims to systematically assess the evidence from randomized controlled trials (RCTs) on self-applied topical interventions for melasma.