Melasma

A 2022 meta-analysis of randomized, investigator-blinded trials found hydroquinone and triple combination cream effective at lightening melasma, with the triple combination consistently outperforming monotherapies. A 2020 evidence-based review covering 113 studies and 6,897 participants reached the same conclusion: triple combination cream is the most effective topical treatment, with hydroquinone alone close behind. Typical regimens are 4% once or twice daily for 8 to 12 weeks.

A 2022 meta-analysis of randomized, investigator-blinded trials found tretinoin effective at lightening melasma as monotherapy, though the triple combination cream (hydroquinone plus tretinoin plus a corticosteroid) consistently outperformed single agents. As a standalone treatment it works more slowly than hydroquinone, often needing 24 weeks or more, so it is usually a supporting player rather than the lead.

In a 16-week double-blind split-face RCT in 16 women, 4% hydroquinone beat 5% ascorbic acid on subjective improvement (93% versus 62.5% good-to-excellent), but objective color measurements showed no statistical difference, and vitamin C caused side effects in only 1 of 16 patients versus 11 of 16 for hydroquinone. The 2023 systematic review supports it as a gentler second-line option, often used alongside other agents rather than alone.

A double-blind split-face RCT in 27 melasma patients compared 4% niacinamide with 4% hydroquinone for 8 weeks: good-to-excellent improvement in 44% of patients on the niacinamide side versus 55% with hydroquinone, with no statistical difference on colorimetry and fewer side effects (18% versus 29%). One small trial is not a large evidence base, but it positions niacinamide as a gentler alternative for mild cases.

A 2023 meta-analysis of 6 RCTs with 673 melasma patients found azelaic acid may reduce melasma severity (MASI score) more than hydroquinone, with no difference in side effects. Individual trials used 20% cream over 8 to 24 weeks. The trials are older and of mixed quality, which keeps this at moderate rather than strong.

A 2024 meta-analysis of randomized controlled trials found TXA significantly reduced melasma severity (MASI) across routes, with oral dosing strongest, followed by injected and topical use. Reviews of comparative trials report topical TXA achieving pigment reduction comparable to hydroquinone with fewer irritant reactions. Most topical trials run 8 to 12 weeks at 2 to 5%; the number of high-quality topical-only RCTs is still modest, which keeps this below a strong grade.

A 2024 systematic review of 24 studies (15 RCTs, 1,075 patients) found peels safe and effective for melasma, with glycolic acid showing the best balance of efficacy and tolerability and outperforming TCA on severity scores. A 2020 meta-analysis in dark-skinned patients supports peels as an adjunct to sunscreen and topical lighteners rather than a standalone cure. Recurrence is the weak point: one series in darker skin reported about 70 percent recurrence by week 12 after stopping treatment.

A 2020 systematic review of 8 studies concluded that microneedling may help melasma, but rated the evidence low quality, and most positive results came from microneedling used as a delivery vehicle for drugs like tranexamic acid rather than on its own. A 2025 meta-analysis of randomized trials of microneedle-assisted therapy found benefits starting around week 4 with best results near week 24, again mostly in combination protocols. Melasma also recurs readily, so any gains need maintenance and strict sun protection.