DENVER — The landscape of topical therapies for melasma is evolving quickly as a steady stream of new agents becomes available, offering alternatives to traditional frontline strategies, a dermatologist told colleagues at the American Academy of Dermatology (AAD) 2026 Annual Meeting. 

“Every year it’s like I need more time for this talk because there’s more and more that keeps coming out, which is wonderful because we need options for our melasma patients,” said Nada Elbuluk, MD, MSc, assistant professor of dermatology at the University of Southern California Keck School of Medicine, Los Angeles, in a presentation of the data. 

But she cautioned that more research is needed to confirm the effectiveness of some new treatments. 

Here’s a closer look at Elbuluk’s guidance.

Traditional Topical Therapies: Still the First-Line Standbys

Hydroquinone, retinoids, steroids, and triple combination creams remain the backbone of first-line treatment for melasma, Elbuluk said.

A focus on alternative treatments shouldn’t make anyone scoff at traditional therapies, she said. “I don't want you to think it’s because we don’t use them, or we don’t love them, because we do. They are our workhorses.”

Elbuluk highlighted a 2019 evidence-based review that found triple combination cream (hydroquinone, tretinoin, and corticosteroid) and hydroquinone alone were the most effective melasma treatments. “These are still mainstays when used appropriately,” she said. 

Azelaic Acid: Multifaceted Relief

“One of my favorite non-hydroquinone agents is azelaic acid, and that’s because it plays multiple roles. Not only is it anti-inflammatory; it’s an antioxidant and it’s anti-melanogenesis,” Elbuluk said. “We are targeting the melanin production, but we’re also targeting inflammation. I like it because it tends to be very well tolerated, especially if you have someone who has sensitive skin or also has some rosacea or is redness-prone.”

Elbuluk noted that several studies positively compare azelaic acid to both 2% and 4% hydroquinone. “I use this a lot, often in combination with other ingredients.”

Kojic Acid: Best in Combination Therapies

Although kojic acid isn’t ideal as a monotherapy, it works well as part of combination therapy with agents such as azelaic acid, Elbuluk said. “It also has antimicrobial and antiaging properties and tends to be fairly well tolerated.”

Tranexamic Acid: ‘A Great Ingredient’

“There’s no melasma talk in the last few years that you go to without hearing about tranexamic acid,” Elbuluk said. “It’s a great ingredient and very exciting for us. It’s not just targeting melanin; it's also targeting the vascularity.”

She noted that “studies have shown that [the oral version] is more effective in general than topicals, and when it’s done as an injection, you tend to get more benefit. With that said, we still do topicals, and there's still a place for them.” 

Side effects include irritation, erythema, scaling, and xerosis. 

Elbuluk highlighted a 2023 expert consensus that found the treatment to be well tolerated and liked by patients, although results are mixed compared with hydroquinone. 

Cysteamine: Helpful but Smelly

This antioxidant decreases tyrosinase activity and inhibits melanogenesis. “There is some complaint by some patients about the smell of it, and some patients have trouble with tolerability,” Elbuluk said. However, “most people actually like it, and they feel it’s helpful.”

Several meta-analyses and systematic reviews in recent years have supported the efficacy and safety of cysteamine, she noted. However, findings have been mixed regarding its efficacy compared with hydroquinone. 

Malassezin and 2-MNG: Promising and Unique

Malassezin stands apart from other therapies because it suppresses melanogenesis, Elbuluk said. Recent proof-of-concept research showed rapid response in patients with melasma and photodamage with minimal adverse effects, she said, and a small 2026 randomized controlled trial found its efficacy similar to hydroquinone over 12 weeks. 

According to Elbuluk, 2-mercaptonicotinoyl glycine (2-MNG) also works in a unique way, inhibiting both eumelanin and pheomelanin synthesis. A 2025 study found that 0.5% 2-MNG to be noninferior to 4% hydroquinone and better tolerated, she said, and another 2025 trial reported that 2-MNG combined with vitamin B₃ had similar efficacy to the standby of Kligman's triple combination cream but was better tolerated. 

Now, she said, 2-MNG is showing up in products such as sunscreens and moisturizers.

Thiamidol: The Hot Newcomer

Thiamidol is “the hot new ingredient that we're all excited about,” Elbuluk said.

“This is actually the most potent inhibitor of human tyrosinase,” she said, highlighting a 2023 systematic review that reported significant pigment reduction when 0.1%-0.2% thiamidol is used at least two to four times daily for 12-24 weeks. Other research is also promising, she said.

Other New Agents

Elbuluk listed several newer agents with promising early data: methimazole, metformin at concentrations of 15%-30%, and glutathione. Others being studied include exosomes; silymarin; lotus sprout extract; resveratrol; MITF-siRNA; omeprazole; isoniazid; carotenoids; and a branded product, Pycnogenol.

Botanical Lighteners: Mind the Evidence Gap

Many botanicals are used in cosmeceutical products, Elbuluk said, and many have lightening properties. But the evidence is weak because randomized controlled trials and standardized outcomes are elusive, she added. 

Big Picture: Combinations Are Where It’s At

“There is no single monotherapy workflow that we use for melasma,” Elbuluk said. “It is a tough condition. We are often combining topicals with other topicals.”

And, she said, there are nontopical options such as photoprotection and procedures. 

Elbuluk disclosed relationships with AbbVie, Beiersdorf, Canfield, Dior, Eli Lilly, Incyte, Janssen Biotech, Kenvue, La Roche Posay, L'Oréal, McGraw Hill, Pfizer, Sanofi, SkinCeuticals, Takeda, Teva, and Veradermics.