Pilot Study Finds Intradermal Botulinum Toxin A Safe and Effective for Melasma

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A pilot study found intradermal Botulinum Toxin A (BoNT-A) to be safe and effective for melasma treatment.¹ A randomized trial and in vitro study confirmed that the clinical depigmenting benefits do not harm the skin cells or pose any risk for patients.

The randomized, split-face, double-blind, placebo-controlled study (TCTR20250118001) was conducted at Samitivej Sukhumvit Hospital in Bangkok, Thailand. It included 12 female patients with Fitzpatrick skin types III and IV and a clinical diagnosis of melasma. All were between the ages of 20 and 55 and the mean age was 39.8 years. About 42% had a family history of melasma with an average disease duration of 6.1 years.

To be eligible for the study, participants must have had no melasma treatments for at least 1 month prior and no Botox injections for at least 6 months prior. Only 7 patients had previously used Botox injections. One side of the face received injections of BoNT-A while the other was given 0.9% normal saline solution.

The primary outcome was to assess the melasma area and severity index (MASI) score. As secondary outcomes, researchers analyzed 7-point physician global assessment (PGA) scores and patient satisfaction scores. Participants were evaluated at baseline, as well as 2, 4, 8, and 12 weeks after treatment.

After 3 months, MASI scores were significantly lower on the side treated with BoNT-A injection, 2.8 versus 4.5, respectively (p < 0.001). The injection also reduced the MASI score at 2 and 3 months compared to baseline, decreasing from 4.1 to 3.2 (p = 0.01) and to 2.8 (p < 0.001). This equates to a -22% and a -31.7%, respectively.

PGA scores were also lower on the BoNT-A side, with a 3.9 compared to the controlled score of 4.9 at 3 months (p = 0.005). Interestingly, peak effects were seen at 3 months rather than the usual 2 weeks for BoNT-A. These results were confirmed with clinical photos taken before and after treatment.

Patient satisfaction scores were higher on the treatment side for the duration of the entire study, when compared to the control side (p < 0.001). The only reported adverse event was mild erythema, which was observed in 33% of all patients. Furthermore, the in vitro study confirmed that all concentrations of BoNT-A reduced melanin content and tyrosinase activity in UVA-irradiated B16F0 cells without causing cytotoxicity or significant cell death.

No objective measurement methods were used in this study, which could complement future findings. Further research that utilizes higher concentrations of BoNT-A with more frequent doses, longer follow-up periods, and even combination therapies, could be beneficial.

“Higher concentrations of BoNT-A should also be evaluated in vitro,” the authors noted. “However, the dose-dependent relationship observed in our initial in vitro findings implied that higher concentrations of BoNT-A might be more effective for melasma.”

Even with modern advancements in melasma like laser therapeutics, tranexamic acid, and chemical peels, it is difficult to find a long-term treatment that offers consistent and safe results due to the disease’s high relapse rates.² Recent studies have confirmed that BoNT-A reduced UVB-induced pigmentation and decreased the melanin index in healthy skin.³ However, this study is the first of its kind in evaluating the BoNT-A injection specifically for the treatment of melasma.

References

1. Thanasarnaksorn W, Supasiri T, Panich U, Thanachaiphiwat S, Salakshna N. Intradermal botulinum toxin A for Melasma: A randomized split‐face study trial and in vitro study of its antimelanogenic effect. Dermatologic Therapy. 2025;2025(1). doi:10.1155/dth/5550483

2. Gan C, Rodrigues M. An Update on New and Existing Treatments for the Management of Melasma. Am J Clin Dermatol. 2024;25(5):717-733. doi:10.1007/s40257-024-00863-2

3. Erdil D, Manav V, Türk CB, Kara Polat A, Koku Aksu AE. The clinical effect of botulinum toxin on pigmentation. Int J Dermatol. 2023;62(2):250-256. doi:10.1111/ijd.16522