Emerging topical therapies for melasma: a comparative analysis of efficacy and safety

Melasma, a prevalent acquired hypermelanosis, significantly impacts psychological well-being. It presents as irregular, bilateral patches of brown or gray skin discoloration and currently lacks a curative treatment. Management focuses on controlling disease progression and preventing further hyperpigmentation through photoprotection, topical and oral medications, and dermatological procedures such as chemical peels, lasers, and microneedling.

This review draws upon extensive literature from PubMed and Google Scholar to critically evaluate and compare the safety and efficacy of topical treatments for melasma, highlighting both established and emerging agents. The Melasma Area and Severity Index (MASI) was used as the primary outcome measure to assess treatment effectiveness.

Among chemical agents, thiamidol demonstrated comparable efficacy to hydroquinone with a better tolerability profile in multiple randomized studies. Tranexamic acid and metformin showed similar MASI score improvements to triple-combination therapy with fewer adverse effects. Natural agents such as niacinamide, kojic acid, and ascorbic acid also demonstrated meaningful pigment reduction with superior safety profiles, supporting their potential role in maintenance therapy. Hydroquinone remains the gold-standard topical treatment despite its known side effects.

Several alternative topical agents show promise and warrant further rigorous, large-scale clinical trials to establish their long-term safety and efficacy.