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Topical Therapies
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.
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1. Comparative study of hydroquinone-free and hydroquinone- based hyperpigmentation regimens in treating facial hyperpigmentation and photoaging. J Drugs Dermatol. 2013 Mar;12(3):S32-7.10
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.
2. Thornfeldt C, Rizer RL, Trookman NS. Blockade of melanin synthesis, activation and distribution pathway by a nonprescription natural regimen is equally effective to a multiple prescription-based therapeutic regimen. J Drugs Dermatol. 2013 Dec;12(12):1449-54.17
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