A Revolutionary Combination for Hyperpigmentation

Treating hyperpigmentation disorders such as melasma has been a difficult challenge over the years. The predominant treatment option, the hydroquinone- and corticosteroid-based Kligman’s formula, brings with it various concerns regarding long-term safety.

In recent years, cysteamine has been shown to be a promising option for hyperpigmentation, and Scientis, the company that first stabilized the molecule, has since improved the formulation by incorporating a new molecule to multiply the efficacy.¹ 

Cyspera Cysteamine Isobionic Amide Complex™, a new topical technology from Scientis SA, has been shown to be as effective as the gold standard but with fewer safety concerns.¹ Additionally, it has been suggested that isobionic amide’s soothing action may help to support inflammation-prone skin types in maintaining their barrier after irritative stress.²

Corey L. Hartman, MD, FAAD, a board-certified dermatologist and assistant clinical professor of dermatology at the University of Alabama School of Medicine, has successfully utilized the Cyspera Cysteamine Isobionic Amide Complex™ in combination with a picosecond laser.³ Dr. Hartman spoke to Modern Aesthetics about the advantages of this treatment combination and strategy.

WHAT CHALLENGES WERE INVOLVED WITH USING KLIGMAN’S FORMULA TO TREAT MELASMA?

Kligman’s formulation includes hydroquinone, a topical steroid, and a retinoid. Hydroquinone is known to be cytotoxic, and there are concerns about it causing cancer in animals and laboratory scenarios. It also does not provide a natural-looking evening of the skin; it crudely lightens the skin in a way that is not even. If you are not careful about applying it directly to the dark spots, a halo of hypopigmentation can appear around the hyperpigmentation, which looks even worse. Beyond the hydroquinone component, steroids can help to penetrate the skin more effectively, but their long-term side effects limit the use of Kligman’s formula.

WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF CYSTEAMINE?

The main disadvantage is the smell. It can also be mildly irritating for certain patients, which is why it is applied in a short contact method. The advantages, meanwhile, are that it is not cytotoxic, it provides a natural evening of the skin tone, the skin has a nice glow afterward, it only needs to be applied once daily, and it works relatively quickly in 12 to 16 weeks.

WHY DOES ISOBIONIC AMIDE WORK SO WELL AS A COMPLEMENT TO CYSTEAMINE IN THE FORMULATION OF THE CYSPERA CYSTEAMINE ISOBIONIC AMID COMPLEX™?

Isobionic amide is a more potent analog of niacinamide, a calming agent. By helping to soothe irritation-prone skins, it targets one of the contributors to uneven pigmentation. Isobionicamide has also been shown to synergistically boost the brightening effect of cysteamine.⁴ I love Cyspera because it works in the background to keep the skin tone even. Once a patient gets past the temporary smell, it is easy to incorporate into a busy lifestyle because it only needs to be used once daily before the shower, or it can even be applied over makeup.

WHAT ARE THE BENEFITS OF USING THE CYSPERA CYSTEAMINE ISOBIONIC AMIDE COMPLEX™ IN COMBINATION WITH LASER TREATMENT?

Laser treatment—particularly in darker phototypes or skin prone to chronic hyperpigmentation—carries a risk of rebound pigmentation, especially when melanocyte activity is not adequately controlled. Pre-conditioning the skin with the Cyspera® Cysteamine IsobionicAmide Complex™ for 2 to 4 weeks may help modulate melanocyte activity and soothe the skin’s low-grade inflammatory state, optimizing the skin’s response to laser energy. In my clinical practice, this approach has shown favorable outcomes, including improved tolerance and reduced incidence of post-inflammatory hyperpigmentation in darker skin types. The Cyspera® Cysteamine Isobionic Amide Complex™ can also be resumed a few days after laser treatment to enhance post-procedure benefits such as skin brightness, radiance, and improved smoother texture. 

1. Sachdev M, Grimes PE, Callender V, et al. Cysteamine Isobionic-Amide Complex Versus Kligman’s Formula for the Treatment of Melasma: Equal Efficacy and Rapid Onset of Action. J Drugs Dermatol. 

2. Liu R, Tsai TF, Lai YJ, Ng 黃昭瑜 CY. Efficacy and safety of cysteamine-isobionicamide complex in postinflammatory hyperpigmentation: A 16-week, randomized, double-blinded, vehicle-controlled trial. Dermatologica Sinica. (2023) 29;41:222–30.

3. Hartman CL, et al. Successful Treatment of Recalcitrant Melasma with Picolaser and Isobionicamide-Cysteamine Combination. J Clin Aesthet Dermatol

4. Dirlewanger L, Mariwalla K, Hartman CL, et al. Isobionic-amide as a new skin depigmenting molecule and its synergistic depigmenting action in combination with Cysteamine: in vitro and clinical results. Frontiers in Medicine, under review.