Thiamidol in Melasma in Patients of Skin of Color: A Preliminary Report of Efficacy and Safety

Abstract

Background:

Melasma poses significant therapeutic challenges, especially in patients with skin of color, due to the increased risk of post-inflammatory hyperpigmentation. Thiamidol, a novel topical tyrosinase inhibitor, has demonstrated potential efficacy with a favorable safety profile in treating hyperpigmentation disorders.

Objective:

This case series evaluates the efficacy and safety of Thiamidol in women of skin of color with melasma.

Patients and Methods:

Ten Indian women with Fitzpatrick skin types III–V and melasma applied 0.2% Thiamidol twice daily for 12 weeks. Outcomes were measured using the modified Melasma Area and Severity Index (mMASI) and patient satisfaction scores.

Results:

The average reduction in mMASI was 34.4%, with patient satisfaction averaging 62%. Reported adverse effects were minimal and self-limiting.

Limitations:

A small sample size and the lack of a control group limit generalizability of the results. Future research should explore thiamidol’s efficacy in combination therapies and assess its long-term benefits.

Conclusion:

Thiamidol is a promising and well-tolerated treatment for melasma in patients with skin of color.

Introduction

Melasma is a common chronic pigmentary disorder, particularly prevalent in skin of color (Fitzpatrick types III–V). Thiamidol, a potent tyrosinase inhibitor, has shown promising results in treating melasma. In a 24-week randomized controlled trial, thiamidol significantly improved melasma compared to vehicle, with effects persisting during follow-up.[1] Another study found thiamidol more effective than hydroquinone in reducing melasma severity, with 79% of subjects showing improvement, and none experiencing worsening.[2] Lima et al.[3] also reported on thiamidol efficacy and safety compared to 4% hydroquinone cream for facial melasma. Thiamidol was well-tolerated and perceived positively by patients in both studies.

Patients and Methods

Ten Indian women aged 25-48 years with Fitzpatrick types III–V with mild to moderate epidermal melasma diagnosed clinically, dermoscopically, and using Wood’s lamp were enrolled. The diagnosis of melasma was established clinically based on characteristic hyperpigmented macules distributed symmetrically on the sun-exposed areas of the face. This was further confirmed using Wood’s lamp examination to assess the depth of pigmentation, and dermoscopy to evaluate reticular or reticulo-globular brown pigmentation, characteristic of melasma. The patients with epidermal melasma were recruited for the study. Differential diagnoses, such as facial acanthosis nigricans, pigmented contact dermatitis, maturational pigmentation, lichen planus pigmentosus, exogenous ochronosis, nevus of Ota, and freckles or lentigines, were excluded, based on the absence of their characteristic clinical features, patient history, and findings of Wood’s lamp examination, which confirmed the diagnosis of epidermal melasma. Further dermoscopy showed accentuation of pseudo-reticular network and reticulo-globular brown pigmentation, corresponding to melanin deposition in the epidermis and dermis, with an absence of perifollicular scaling or accentuation. This distinguishes melasma from facial acanthosis nigricans, which shows linear or band-like pigmentation with velvety texture, while pigmented contact dermatitis exhibits perifollicular scaling and irregular pigmentation; maturational pigmentation lacks symmetry and reticular patterns; lichen planus pigmentosus with bluish-gray pigmentation with dots or globules; exogenous ochronosis with gray-brown pigment globules and curvilinear streaks; nevus of Ota with bluish pigmentation extending to mucosae; and freckles or lentigines with discrete, sharply circumscribed pigmented globules. A 4-week washout period was implemented, during which participants used only sunscreen. Thiamidol 0.2% cream was applied twice daily for 12 weeks, followed by sunscreen use during the day. The primary outcome was the modified Melasma Area and Severity Index (mMASI) score and the patient’s satisfaction with therapy was assessed using a subjective scale as follows: poor = 0–25%, fair = 25–50%, good = 50–75% and excellent response rate = 75–100% [Table 1]. We calculated the percentage decrease in mMASI, patient’s satisfaction scores, and the average percentage decrease in mMASI. Further statistical analysis using paired Student’s t-test was done to assess the P value of decrease in mMASI score at 12 weeks.

Table 1.

Case series with modified Melasma Area and Severity Index scores at baseline and at 12 weeks

Age (years)	Sex	Duration of disease	Family history	Treatment history	mMASI at baseline	mMASI at 12 weeks	Percentage decrease in mMASI	Side effects reported	Patient’s satisfaction score
35	F	6 years	Yes	Triple combination x 3 months Topical tranexamic acid plus arbutin combination x 3 months	5.4	3.0	44.4	None	80%
44	F	10 years	No	Triple combination x 3 months Kojic acid and arbutin, combination cream x 2 months	7.2	6.3	12.5	None	40%
45	F	2 years	Yes	None	10.7	5.6	47.7	None	80%
47	F	8 years	No	Triple combination x 3 months Kojic acid, arbutin, vitamin E, and glycolic acid combination cream x 2 months	3.5	2.5	28.6	None	50%
25	F	1 year	Yes	None	11.4	8	29.6	None	60%
39	F	9 years	No	Triple combination x 3 months	8.7	6.4	26.4	None	60%
35	F	10 years	Yes	Triple combination x 3 months Multiple sittings of glycolic acid peels	10.2	7.6	25.7	None	60%
43	F	5 years	No	None	8.3	6.3	23.5	None	50%
48	F	10 years	No	Triple combination x 3 months Oral tranexamic acid x 3 months Kojic acid, arbutin, vitamin E, and glycolic acid combination cream x 6 months	1.8	0.4	77.8	None	80%
45	F	7 years	No	None	9.3	6.8	27.4	None	60%
The average decrease in mMASI in above 10 patients							34.4%	No patient reported any side effects	62%

F: Female; Triple combination: Hydroquinone 4%, tretinoin 0.05%, flucinolone acetonide 0.01 %

Results

At the end of 12 weeks, all patients showed significant mMASI score reductions (P < 0.001). with a mean reduction of 34.4%. Patient satisfaction scores were fair to good, with an average score of 62%. None of our patients reported any side effects. Higher satisfaction rates were attributed by the patients to no side effects, including burning, stinging, hypopigmentation, etc., which were present with previously used treatment regimens. Figures 1-6 show baseline and post-12 weeks clinical photographs of 3 of the patients.

Figure 1.

Clinical image of patient 3 at baseline

Figure 6.

Clinical image of patient 5 after 12 weeks of thiamidol use

Figure 2.

Clinical image of patient 3 after 12 weeks of thiamidol use

Figure 3.

Clinical image of patient 4 at baseline

Figure 4.

Clinical image of patient 4 after 12 weeks of thiamidol use

Figure 5.

Clinical image of patient 5 at baseline

Discussion

Thiamidol, a selective tyrosinase inhibitor, has shown significant promise in the treatment of melasma, offering an alternative to traditional therapies, such as hydroquinone.[1,2,3] It is a novel agent and only a few studies have tried to evaluate its efficacy in melasma, and none of them have evaluated its safety and efficacy in skin of color. Our study confirms the findings of previous studies showing the potential clinical benefits of thiamidol in mild to moderate epidermal melasma in patients with skin types III–V.

Hydroquinone remains a gold standard for melasma treatment, but is often associated with limitations, including irritant dermatitis, rebound pigmentation, and a strict usage duration of three months to avoid severe side effects. Thiamidol has demonstrated comparable or superior efficacy to hydroquinone in reducing melasma severity.[2,3] Previous studies indicate a significant reduction in mMASI scores with thiamidol use over 12 weeks, with improvements observed as early as four weeks.[2] The percentage of subjects showing clinical improvement was consistently higher with thiamidol (79%) compared to hydroquinone (61%).[2] This efficacy is attributed to its potent inhibition of human tyrosinase, which is a key enzyme in melanin synthesis. Unlike hydroquinone, which has cytotoxic effects on melanocytes, thiamidol selectively inhibits tyrosinase without causing melanocyte damage.[4] Thiamidol does not cause ochronosis or paradoxical hyperpigmentation, complications that are occasionally seen with hydroquinone.[3] Additionally, its nontoxic mechanism of action broadens its applicability across different skin types and tones.[2] These findings suggest that thiamidol is well suited for long-term use in melasma in skin of color. However, previous reports indicate a low incidence of side effects, such as mild stinging, transient erythema, or slight burning sensations, during the initial weeks of treatment.[1,2,3] These effects were self-limiting and did not lead to treatment discontinuation. A favourable safety profile is one of the most compelling advantages of thiamidol, which is emphasized by our study where none of our participants reported any adverse effects.

Further compared to other depigmenting agents, such as kojic acid and arbutin, thiamidol has demonstrated superior efficacy in vitro.[4] The findings from our study and previous studies position thiamidol as a promising first-line therapy for melasma, particularly for patients with skin of color, who are at greater risk of complications from conventional treatments. Its ease of application, lack of severe adverse effects, and consistent efficacy across skin types highlight its potential to improve treatment adherence and outcomes in this population. Future research should aim to explore combination regimens involving thiamidol with other therapies, such as tranexamic acid, antioxidants, or microneedling. Long-term studies are also needed to assess its role in preventing relapses and its effectiveness in other pigmentary disorders beyond melasma.

Limitations

This study’s small sample size and lack of a control group limit generalizability.

Conclusion

Thiamidol represents a significant advancement in the management of melasma, offering a safe, effective, and patient-friendly alternative to traditional depigmenting agents. Its selective inhibition of tyrosinase, coupled with its excellent safety profile, positions it as a valuable tool for clinicians addressing the challenges of hyperpigmentation, especially in skin of color. Further studies are warranted to establish its long-term benefits and optimize its use in clinical practice. Future research should explore thiamidol’s efficacy in combination therapies and assess its long-term benefits.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence (AI)

The preparation of this manuscript was carried out entirely by the author without the use of artificial intelligence technologies.

Funding Statement

Nil.