Understanding Melasma Treatments

Melasma is a skin condition that is characterized by hyperpigmented spots on the skin. Melasma is sometimes referred to as chloasma.

The spots are most frequently found on the face and can vary in color from barely visible light-brown spots to more visible dark brown spots, and in some cases, the spots can show up in a blue-gray tone.

There are several treatment options available to help reduce the appearance of dark spots.

Protection from Ultraviolet Light

There is no cure from melasma, but there are small changes that can help minimize the chances of aggravating melasma.

Studies have shown that ultraviolet (UV) light from the sun can aggravate melasma. Visible light sources including the exposure to fluorescent light bulbs and digital screens such as cell phones, computers, or even flat screen TVs can also exacerbate melasma.

In order to minimize exposure to UV and visible light, people with melasma should apply broad spectrum sunscreen with an SPF of 30 or higher as a part of their daily morning routine and reapply the sunscreen every two hours.

Sunscreens that contain iron oxide can improve the Melasma Activity and Severity Index (MASI) scores. Sunscreens with titanium oxide and zinc oxide can also provide protection for patients with melasma but may leave a visible layer of lotion on people with darker skin.

Wide-brimmed hats, baseball caps, and bucket hats can also help protect against UV light.

Topical Medications

There are several topical medications that can help speed up the fading of the melasma spots.

The majority of clinically-proven topical therapies require a dermatologist’s prescription.

Below are some of the topical medications that have been clinically proven to help treat melasma.

Tyrosinase Inhibitors

Tyrosinase is the enzyme responsible for melanogenesis, which is the process of producing pigment melanin in the skin.

In lay terms, tyrosinase gives color to the skin and inhibiting tyrosinase can stop the patches from developing. A comprehensive review of the therapeutics that have been shown treat melasma includes the following tyrosinase inhibitors:

• Azelaic acid – Treatment with azelaic acid 20% showed significant improvement in MASI scores during the 24 weeks of treatment.
• Hydroquinone – Daily treatment with hydroquinone 4% is the gold standard for topical skin lightening. This is typically the first line of therapy for people with melasma.
• Kojic acid – A 12 week clinical study comparing the daily application of 0.75% kojic acid cream to 4% hydroquinone in 60 patients with melasma found that both treatment groups saw significant improvement of the MASI scores after 8 weeks of treatment. However, patients who were treated with 4% hydroquinone had overall better results compared to patients treated with kojic acid.
• Licorice – A clinical study of 20 women with melasma found that the daily application of topical liquiritin 20% twice a day for 4 weeks led to improvement of melasma in 70% of the patients.
• Mequinol – A small clinical study of 5 men with melasma who were treated with mequinol 2% and tretinoin 0.01% showed that four out of five patients had complete clearance at 12 weeks of treatment.
• 4-N-Nutylresorcinol (4NBR) – Eight weeks of twice daily treatment with 4-n-Butylresorcinol 0.1% cream or vehicle showed significant improvement in 60% of patients. These results were part of a split-face study of 23 patients with melasma

It is important to note that some of these clinical studies include a small number of patients. 

Other topical medications that have shown to be effective therapies for treating melasma include tretinoin and corticosteroids.

Always consult a dermatologist to consider which treatment option would work best for you. It is especially important to consult a healthcare professional before beginning any treatment when the melasma is caused by pregnancy to ensure the medication is safe to use during pregnancy.

Systemic Treatments

The most popular systemic treatment for people with melasma is oral tranexamic acid.

The dosage typically varies from 500-750 mg daily but may be lower when used in combination therapies.

Several studies have validated oral tranexamic acid use for the treatment of melasma, with some clinical studies showing a response rate of up to 89.7% of patients treated with oral tranexamic acid.

Treatment with oral tranexamic acid can cause some serious side effects including thromboembolic events. Some of the more common side effects include gastrointestinal issues, headaches, and menstrual irregularities.

Methimazole is an oral antithyroid compound that is applied topically. About 70% of patients treated daily with methimazole 5% cream were satisfied with the results of the 12-week treatment in a study of 30 Egyptian patients with melasma.

Several studies have shown that methimazole may not be as effective for the treatment of melasma as treatment with hydroquinone 4% but may be better tolerated.

Combination Therapies 

Some medications work best when combined to reduce the appearance of melasma. Using a combination therapy of 250 mg of oral tranexamic acid taken daily in combination with the topical application of the liposomal form of azelaic acid 20% provided a 66.9% improvement in MASI scores of the patients treated with both medications.

The study compared the treatment with liposomal azelaic acid 20% and oral tranexamic acid to a combination treatment of hydroquinone 4% with oral tranexamic acid.

Both treatment groups saw improvement in the MASI scores and in overall quality of life. The group that used the azelaic acid 20% and 250 mg oral tranexamic acid saw the best results.

The triple combination cream, Tri-Luma; fluocinolone acetonide 0.01%, HQ 4%, tretinoin 0.05%, is the only FDA-approved melasma treatment with 3 active ingredients.

The three-ingredient combination cream includes a corticosteroid, a retinol, and a Tyrosinase inhibitor and is intended for short-term use in people with melasma. Women who are pregnant or trying to become pregnant should not use the cream.

In-Office Treatment Procedures

There are some minor in-office treatment procedures that can help reduce the appearance of melasma:

• A chemical peel involves using a chemical agent to burn the skin. Some of the common peeling agents include trichloroacetic acid, glycolic acid, salicylic acid tretinoin, and Jessner’s solution. Chemical peels are effective for reducing the appearance of spots but are also considered a second-line agent. In some people, chemical peels may aggravate melasma. 
• A microdermabrasion is a procedure that gently exfoliates the skin by using sand or a different type of small crystal to resurface the skin. Microdermabrasion has been shown to be a safe and effective treatment to help reduce the appearance of melasma. 
• A typical third-line treatment option for melasma is laser therapy. Laser therapy, or laser resurfacing, requires the use of a laser at a specific wavelength to target the epidermal and dermal layers of the skin. Laser therapy options include Q-switch laser, picosecond lasers, non-ablative fractionated resurfacing lasers, and ablated fractionated resurfacing lasers. Laser therapies have shown to be effective treatments for patients that do not see improvement after using topical creams or other second-line treatments such as chemical peels, or microdermabrasion. Laser therapies can cause melasma rebound in some patients.  
• Intense pulsed light (IPL) is a type of light therapy that has been shown to be helpful for patients with moderate to severe melasma. IPL can be used to treat larger areas of the face. While IPL is effective, it can lead to the development of other hyperpigmentation skin conditions or leave a crust on the skin that lasts up to 2 weeks after the treatment. 

There is no cure for melasma but there are several treatment options that can help reduce the appearance of melasma.

It is important to meet with a dermatologist to discuss which treatment options are most beneficial for your specific needs.

Women who are pregnant or planning to become pregnant should discuss their pregnancy plans with their doctor as several of the treatment options are not safe to use during pregnancy or for women who are nursing.

Some women who developed melasma spots during pregnancy may notice that the spots fade after pregnancy. 

Several of the clinical studies mentioned in this article show that while some treatment options work well for some patients, they can also exacerbate melasma in others.

Some patients may see that melasma spots fade on their own by regularly using sunscreen and limiting sun exposure. Always seek advice from a medical professional before beginning any treatment. 

References, Studies and sources:

1. Melasma – Cleveland Clinic
2. Huerth KA, Hassan S, Callender VD. Therapeutic Insights in Melasma and Hyperpigmentation Management. J Drugs Dermatol. 2019;18(8):718-729.
3. Zolghadri S, Bahrami A, Hassan Khan MT, et al. A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2019;34(1):279-309. doi:10.1080/14756366.2018.1545767
4. Akl EM. Liposomal azelaic acid 20% cream vs hydroquinone 4% cream as adjuvant to oral tranexamic acid in melasma: a comparative study [published online ahead of print, 2021 Apr 7]. J Dermatolog Treat. 2021;1-6. doi:10.1080/09546634.2021.1905765
5. Monteiro RC, Kishore BN, Bhat RM, Sukumar D, Martis J, Ganesh HK. A Comparative Study of the Efficacy of 4% Hydroquinone vs 0.75% Kojic Acid Cream in the Treatment of Facial Melasma. Indian J Dermatol. 2013;58(2):157. doi:10.4103/0019-5154.108070
6. Amer M, Metwalli M. Topical liquiritin improves melasma. Int J Dermatol. 2000;39(4):299-301. doi:10.1046/j.1365-4362.2000.00943.
7. Keeling J, Cardona L, Benitez A, Epstein R, Rendon M. Mequinol 2%/tretinoin 0.01% topical solution for the treatment of melasma in men: a case series and review of the literature. Cutis. 2008;81(2):179-183.
8. Huh SY, Shin JW, Na JI, Huh CH, Youn SW, Park KC. Efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream for the treatment of melasma: a randomized controlled split-face trial. J Dermatol. 2010;37(4):311-315. doi:10.1111/j.1346-8138.2010.00787.x
9. Rajanala S, Maymone MBC, Vashi NA. Melasma pathogenesis: a review of the latest research, pathological findings, and investigational therapies. Dermatol Online J. 2019;25(10):13030/qt47b7r28c. Published 2019 Oct 15.
10. Farag A, Hammam M, Alnaidany N, et al. Methimazole in the Treatment of Melasma: A Clinical and Dermascopic Study. J Clin Aesthet Dermatol. 2021;14(2):14-20.

Kate Byrd, PharmD( Medical Writer, Editor,and Contributor )

Kate Byrd, PharmD, is a highly accomplished Medical Writer with a strong background in pharmacy and an unwavering commitment to producing accurate, informative content. After earning her Doctor of Pharmacy degree, Kate embarked on her career as a Medical Writer, where she has since gained valuable experience in developing evidence-based content that translates complex medical information into easy-to-understand articles. We are thrilled to announce that Kate is now bringing her expertise and dedication to the medical writing team at Pharmacists.org. Her passion for empowering readers with reliable and accessible health information aligns perfectly with our mission, making her a valuable addition to our team.