Melasma Treatment: An Evidence-Based Review

Jacqueline McKesey; Andrea Tovar-Garza; Amit G. Pandya


Am J Clin Dermatol. 2020;21(2):173-225. 

In This Article


Although there have been many studies in subjects with melasma, the majority have used subjective outcome measures; only a small number of studies included objective outcomes. The most common outcome measures were based on clinical examination, photographic evaluation, and/or Wood's lamp examination. The most common scoring system used was the MASI score, followed by mMASI. The latter includes the analysis of the percentage of area affected by melasma in four different areas of the face, and darkness. Another scoring system utilized was the melasma severity scale, however this is a non-validated outcome measure. Comparison across studies was difficult as many articles included a variation on non-specific ratings, such as 'poor', 'excellent', or 'moderate'. Objective outcomes were used in some studies, including reflectance spectrophotometry. A few studies also included histopathological analysis of melanin content and blood vessels in the dermis. Several split-face studies used a mMASI score that included only the analysis of the malar surface involved instead of the entire face, as used in traditional methods. Better studies using validated and objective outcome measures, large sample size, and longer follow-up are needed.


Topical HQ continues to be the most extensively studied treatment for melasma. Despite theoretical risk of adverse effects, multiples studies have demonstrated its excellent safety profile. TCC continues to be the most effective treatment for melasma, and safety has been established in studies of daily use up to 12 months. Furthermore, a tapering regimen of TCC seems to be slightly less effective than a twice-weekly protocol for maintenance therapy of TCC, although a twice-weekly regimen may still result in relapse. Relapse rates seem to be most closely tied to severity of melasma at baseline. Multiple variations of the original formulation of TCC have been made to decrease adverse effects, particularly the tretinoin component, which is the most irritating component. The use of sunscreen with SPF ≥ 30 is mandatory in the management of melasma, and, recently, the use of iron oxide-containing sunscreen to provide additional protection from visible light has been advocated.[141]

Other depigmenting agents, such as topical TXA, have not shown higher efficacy when compared with HQ. However, microneedling using TXA has shown promising initial results. Furthermore, microneedling may be a valuable tool for assisting drug delivery to the skin in lieu of laser therapy or chemical peels, which may induce PIH.[142] AA was found to be more effective than 2% HQ, but equivalent to 4% HQ cream, although it garnered more adverse effects. Vitamin C has been shown to decrease skin pigmentation and could be used as an alternative treatment when HQ is not an option. Topical tretinoin 0.05–0.1% has shown mixed results, with most studies showing efficacy; however, longterm use is necessary for clinical improvement.

The chemical peels reviewed did not show consistent results. GA peels and SA peels were not found to be more effective than HQ. TCA peels combined with Jessner's solution could be a promising alternative in recalcitrant melasma, but larger, controlled studies are needed. A major problem with chemical peels is the risk of erythema, burning, and PIH. Therefore, use of peels should only be considered as a second-line treatment and they must be used cautiously in dark-skinned subjects.

Laser- and light-based devices have yielded mixed results. IPL has been shown to improve melasma, however concomitant use of HQ or TCC is recommended to decrease the risk of rebound. QS-Nd:YAG has not been found to be more effective than HQ, and risk of mottled hypopigmentation is present. Low-fluence QS-Nd:YAG has shown higher efficacy than 2% HQ, but, again, carries the risk of mottled hypopigmentation. PDL laser is the only treatment that has shown decrease in the relapse of melasma, mainly targeting the vascular component of melasma. Fractional photothermolysis has a high risk of PIH and melasma recurrence. Laserand light-based devices should be considered as a third-line treatment for melasma, and should be used judiciously in dark-skinned subjects.

Oral TXA has been shown to be a safe and effective treatment for recalcitrant moderate to severe melasma.


Even with multiple treatment modalities, there is no topical, oral, or light-based monotherapy treatment that guarantees improvement of melasma. The lack of well-designed, placebo-controlled studies makes it difficult to compare treatments and assess statistical significance. Furthermore, this review did not include the myriad of studies reported as case series, reports, and retrospective reviews. Future studies should adhere to validated subjective and objective outcome measures so that comparison across studies can be made. Subjective validated outcome measures include MASI and mMASI scores. Objective assessment can be made by reflectance spectrophotometer, colorimeter, and/or skin biopsies from lesional and non-lesional skin. Quality-of-life measures should also be assessed using validated measures such as the MelasQoL questionnaire.