New and Emerging Treatments for Hyperpigmentation

Topical treatment of hyperpigmentation is largely aimed at reducing the production and distribution of epidermal pigment. The tyrosinase inhibitor, hydroquinone, has long been the gold standard topical agent due to its established efficacy. In melasma, specifically, there is strong evidence for use of 4% hydroquinone as a first-line agent, especially in a triple-combination that includes tretinoin and fluocinolone acetonide.^1,2 However, the risk of exogenous ochronosis from long-term or excessive use of hydroquinone as well as the potential for irritation are limitations of this agent. Safety concerns on the part of regulatory agencies (based on animal studies), and to some extent the general public, have driven a surge in the development of non-hydroquinone containing products for hyperpigmentation. Frequently cited alternatives to hydroquinone that have been used in the treatment of hyperpigmentation disorders include kojic acid, azelaic acid, and the topical retinoids (tretinoin, tazarotene, and adapalene). While published studies involving skin lightening formulations have been reviewed elsewhere,^3-9 a selection of recently published studies involving novel non-hydroquinone topical formulations are summarized below.

In this investigator-blinded, randomized study, the tolerability and efficacy of a hydroquinone-free four-product regimen (cleanser, skin brightening complex containing non-hydroquinone ingredients, sunscreen, and tri-retinol 1.1%) was compared to that of a hydroquinone-based regimen containing seven topical products (cleanser, toner, two hydroquinone 4% formulations, exfoliant, sunscreen, and tretinoin 0.025% cream). The non-hydroquinone containing skin brightening complex consisted of tetrahexyldecyl ascorbate, 4-ethoxybenzaldehyde, retinol, and linoleic acid, glabridin, hexylresorcinol, niacinamide, 4-ethoxybenzaldehyde as active ingredients. Thirty-six female subjects with mottled pigmentation and photodamaged facial skin completed this 12-week comparative study. Outcome measures included an Overall Hyperpigmentation scale and the Mottled Pigmentation Area and Severity Index (MoPASI) at 12 weeks compared to baseline. Both regimens demonstrated comparable efficacy and tolerability.

The use of multiple topical products in combination, albeit a “real world” regimen, is a limitation of this study as the efficacy of the skin-brightening complex alone cannot be evaluated. However, a double blind half-face comparison study including a similar skin brightening complex vs hydroquinone 4% has been published.¹¹

Other recent studies involving the above multi-modal topical formulation have also been recently published.12-16 A study evaluating this formulation in darker skin types with postinflammatory hyperpigmentation would be useful given the high prevalence of this disorder and the efficacy limitations of current treatment options.

This prospective, blinded, controlled trial compared two regimens containing botanical ingredients to one containing 4% hydroquinone and tretinoin. The natural ingredient regimens were designed to use a combination of agents that inhibit melanogenesis at multiple steps. 56 female subjects with mild to