Intradermal Botulinum Toxin A for Melasma: A Randomized Split-Face Study Trial and In Vitro Study of Its Antimelanogenic Effect

Background: Melasma is a challenging hyperpigmentation disorder without absolute treatment. Aims: This study aimed to evaluate the effects of intradermal botulinum toxin A (BoNT-A) on melasma and the protective effects of BoNT-A on UVA-induced melanogenesis in B16F10 melanoma cells. Patients/Methods: This study is a split-face randomized, double-blind, placebo-controlled trial in 12 melasma patients who received intradermal abobotulinumtoxinA injection into melasma lesions. An in vitro study was also conducted in B16F10 melanoma cells treated with different concentrations of BoNT-A prior to exposure to UVA. Cell viability and cellular melanogenesis were determined. Results: The adjusted MASI scores on the BoNT-A side were significantly lower than the control at 3 months after injection, 2.8 versus 4.5 (p < 0.001), respectively. BoNT-A injection significantly reduced the MASI score at 2 and 3 months compared with the baseline of 4.1–3.2 (22%) (p < 0.001) and 2.8 (31.7%) (p < 0.001), respectively. Melanin content and tyrosinase activity in B16F10 cells with or without UVA irradiation were significantly reduced by treatment with BoNT-A in a dose-dependent manner without causing cytotoxicity. Conclusions: BoNT-A has a potentially beneficial effect in the treatment of melasma due to its antimelanogenic effect. Trial Registration: Clinical Trial Registry identifier: TCTR20250118001.