Cyspera is a novel solution for melasma & other types of skin pigmentation. This sulfur based cream has no long term side effects, however it has a high irritant potential, hence learning how to apply it is important.


Pigment corrector

When to use


Works with

Azelaic acid

Caution with

Vitamin C, hydroquinone, retinol

Dermatologist science score

What is Cysteamine or Cyspera?

Cyspera (trade name), cysteamine is an antioxidant naturally present in the human body & breast milk. It is also a powerful pigment inhibitor & has been used to treat melasma & pigmentation. This ingredient is considered as an alternative to hydroquinone and triple combination creams. Cysteamine cream can be used for extended durations and has shown promise in reducing melasma relapses.

How good is it as a pigment corrector?

In commercial publications, cysteamine has shown to be as effective as well-known depigmenting therapies, including triple combination cream or tranexamic acid mesotherapy, with higher tolerability. In real world testing, Cyspera is not as effective as medically prescribed melasma therapy.

Our clinicians however, find this topical as a useful ingredient during rotational therapy, used to reduce the side effects of traditional depigmenting agents.

How to initiate Cyspera for melasma?

Though Cyspera is better tolerated than traditional pigment correctors such as hydroquinone & retinoids, skin irritation is not uncommon. Here is how to use this cream-

  • Start every second day, apply for 15 minutes then wash off
  • Increase by one day a week until daily use tolerated
  • Hold for 16 weeks (once daily dosing)
  • Maintain after with twice a week dosing
  • Incorporate pigment correctors during the maintenance phase

What are the side effects of Cyspera?

Side effects are common with Cyspera, hence why ‘leave on’ time is only 15 minutes. Side effects include-

  • Stinging, burning
  • Redness, swelling
  • Warmth post application
  • Prolonged skin irritation

How to reduce the side effects with Cyspera/ Cysteamine cream?

Increased side effects occur when:

  • The face is washed just before the application (minimum 30 minute interval to be respected)
  • Extended contact time on the skin
  • Concomitant use with other topical products

Limit the application of Cyspera/ cysteamine cream to 15 minutes with a 1 hour interval between washing and application of Cyspera/ cysteamine cream.

How soon can I see results?

Initial results can be seen at 6 weeks with maximal results at week 12 to 16. Studies have shown up to 77% reduction in melasma pigmentation with 90% of users reported moderate to significant improvement in their condition. Refer to the comment below for real time data.

What other treatments do we combine with Cypera – Cysteamine?

Our team at The Melasma Clinic combines Cyspera with other melasma treatments to optimize & accelerate results. These include-

  • Lasers: Picosure Pro, thulium & vascular
  • Chemical peels: Dermamelan, Cosmelan, AHA, retinoic acid
  • Pigment correctors: Vitamin C, arbutin, plant extracts such as bearberry & licorice
  • Vascular modifiers: oral, topical

Can microneedling be used with Cysteamine?

There are several research papers on the use of Cysteamine with microneedling. Microneedling is used to enhance the efficacy & absorption of Cyspera by breachment of the upper layers of skin. Needle depths should not exceed 0.1 to 0.2 mm.

If you are considering microneedling, reduce application of cysteamine as increased absorption means increased irritation. Skin irritation is harder to modulate if you add microneedling to the picture, so be mindful of that.

What other pigmentation conditions can be treated with Cyspera?

Though researched primarily for melasma, Cyspera-cysteamine can be useful to treat post-inflammatory hyperpigmentation & sun induced pigmentation.

How does Cyspera/ Cysteamine melasma cream work?

Cysteamine is a sulfur based cream that inhibits the activity of the tyrosinase & peroxidase. These two enzymes are involved in the key steps of melanin or pigmentation formation. It is also a powerful antioxidant.

When combined with treatments like Pico laser & chemical peels; the pigmentation lightening results are accelerated. Though heralded as a substitute for traditional pigment correctors, it is best used as rotational therapy.

What is rotational therapy for melasma?

Our clinical team will discuss the right timing for Cyspera as part of rotational therapy. Our clinic treats melasma via two phases-

  • Active depigmentation phase: active removal of pigment
  • Maintenance phase: keeping pigment from recurring

The length of rotational therapy varies with each patient as we take into account genetic & environmental factors as well other factors such as background sun damage & skin aging. 

What is the Cyspera Intensive System for 2024?

The new Cyspera Intensive System™ is a 3-step approach to melasma treatment.

It contains-

  • Cyspera® Intensive Pigment Corrector System™ is formulated with a proprietary Cysteamine Isobionic-Amide Complex™, a patented and powerful melanosomal transfer inhibitor that is part of the vitamin B3 family, which along with cysteamine, provides three powerful synergistic effects for improved pigment correction and skin health.
  • Cyspera Neutralize™ (50 ml)
  • Cyspera Boost™ (30 ml)

What is the scientific data on cysteamine for melasma?

Is cysteamine use effective in the treatment of melasma? A systematic review and meta-analysis

Dermatol Therapy 2022 Dec;35(12): 2022 Nov 2.

Agenor Gomes Dos Santos-Neto Ísis Carolline Valério da Silva 3, Carlisson Ramos Melo, Adilson Allef Moraes Santana, , Ricardo Luiz Cavalcanti de Albuquerque-Junior

This review aimed to evaluate the efficacy of the use of depigmenting formulations containing 5% cysteamine in the treatment of patients with melasma.

A systematic search was performed in PubMed, Science Direct, and Scielo databases until December 27, 2021, based on criteria selected by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of six studies containing 120 melasma patients treated with 5% cysteamine were included in this meta-analysis. The meta-analysis demonstrated that 5% cysteamine is effective for the treatment of patients with melasma (MD 6.26 [95% CI 3.68-8.83], p < 0.0001, I2 = 86%). In this review the conclusion was that 5% cysteamine is effective in the treatment of melasma and presents a low probability of side or adverse effects.

Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines

J Drugs Dermatol 2021 Dec 1;20(12):1276-1279.

Seemal Desai, Corey Hartman, Pearl Grimes, Sana Shah

Multiple studies now document that cysteamine is a potent skin depigmenting agent. Historically, its rapid oxidation and very offensive odor made it difficult for topical use until recently when stabilization of cysteamine was achieved. Since 2015, the efficacy, safety, and tolerability of stabilized cysteamine has been demonstrated in multiple clinical studies. Stabilized cysteamine has demonstrated significant effectiveness for the treatment of melasma by two double-blind randomized and vehicl control trials. Stabilized cysteamine has shown to be as effective as well-known depigmenting therapies, including triple combination cream or tranexamic acid mesotherapy, with higher tolerability. Cysteamine can be regarded as one of the most potent treatments available for hyperpigmentation disorders in humans.

Efficacy of topical cysteamine hydrochloride in treating melasma: a systematic review.

Najmeh Ahramiyanpour, Nasrin Saki, Zahra Akbari, , Simin Shamsi-Meymandi , Rezvan Amiri, Alireza Heiran

Cysteamine cream could be comparably efficient in treating melasma while accompanied only by minor and transient adverse events. However, current evidence is limited by insufficient sample size, long-term follow-up, and only to epidermal melasma, highlighting the need for appropriately designed randomized controlled clinical trials to draw a conclusive image of the cysteamine’s role in treating this recalcitrant condition.

The future of melasma therapy
Jul 2022-Dermatological reviews-Vol. 4, Iss: 1, pp 67-74

Lauren C. Payne, Benjamin B. Nia, Valerie D. Callender

Conclusions from the paper

  • Melasma is a chronic dermatologic condition
  • Risk factors for melasma include ultraviolet and visible light exposure, high levels of estrogen, and family history.
  • Treatment options for melasma include topical skin lightening agents (hydroquinone, azelaic acid, kojic acid, ascorbic acid, cysteamine), tranexamic acid (both topical and oral), and procedural treatments (micro-needling, intradermal injections). Combination therapy is often used for maximum benefit.
  • Strict sun protection is crucial to minimize the risk of melasma recurrence, as UV and visible light exposure are common triggers.

Current updates on melasma treatments
May 2023-Cosmoderma-Vol. 3, pp 79-79

Apratim Goel, Nishi S Trivedi

Conclusions from the paper

  • Melasma is a common chronic relapsing pigmentary disorder
  • Treatment options for melasma are numerous and diverse, with each promising better results than the previous ones.
  • Established treatments like hydroquinone and triple combination creams have side effects that limit their long-term use. However,
  • Alternatives such as kojic acid, rucinol, and cysteamine cream have emerged, which can be used for extended durations.
  • Lasers and light therapies have become essential components of melasma management.

Update on Melasma Management
Heidi Oi-Yee Li, E. Pastukhova, Jeffrey S. Dover

May 2023-Advances in Cosmetic Surgery-Vol. 6, Iss: 1, pp 193-211

Conclusions from the paper:

  • Melasma is a complex hyperpigmentary disorder with a multifactorial etiology.
  • Management is diligent photoprotection and topical therapy, such as hydroquinone and triple therapy (hydroquinone, retinoid, and steroid) creams.
  • Additional novel topical treatments can be considered, such as tranexamic acid, cysteamine, azelaic acid, methimazole, metformin, and botanic agents like Rumex occidentalis

A SummaryDavin’s viewpoint on Cyspera for melasma & pigmentation

Dr Davin Lim | Dermatologist
Sydney, Australia | Sydney

We conducted trials on Cysteamine several years ago, & though useful during the maintenance phase of melasma, we hardly use it for the de-pigmentation phase as it is limited by skin irritation & importantly efficacy. Unlike traditional preparations such as hydroquinone, there are no long term complications such as rebound or exogenous ochronosis with Cyspera, hence its use during the maintenance phase of treatment.

There are three rate limiting factors with cysteamine-

  • Skin irritation; hence the use of short contact therapy with a 15 minute ‘on’ time before washing the product off.
  • Traditionally cysteamine cream has been pungent, primarily due to the sulfur like odor which has been rectified with the Cyspera formulation by Scientis.
  • Price; it is not cheap at over $250 AUD or $160 USD.

Overall, this is a useful ingredient in the management of pigmentation concerns.