In short
- 🚨 No pigmentation is treated without knowing what it is. Anything that changes colour, size or border, or that bleeds, is looked at before anything is applied to it. A cream is bought without anyone seeing it, and that is the risk peculiar to this product.
- 🔑 Sun protection is not “an extra”: it is the only front that acts on the cause. Every other active slows the pigment factory down while the stimulus keeps arriving.
- Cosmetic depigmenting agents do not all do the same thing: some inhibit the enzyme that makes melanin, one slows its transfer into the skin and others speed up turnover. Combining mechanisms pays off more than raising the dose of one.
- 🔑 And they do not all have the same evidence. The one that comes off best among those you can buy without a prescription is 5% cysteamine: a meta-analysis of seven randomised trials found no significant difference against 4% hydroquinone.
- 🚨 The two actives with the best comparative evidence are NOT cosmetics. Azelaic acid at medicine-strength concentration and oral tranexamic acid are prescribed by a doctor — and the second, moreover, outside its authorised indications.
- ⚠️ Alpha-arbutin and arbutin have been capped by law since 2025: 2% and 7% respectively in facial creams. And the rule also requires hydroquinone to be kept at unavoidable trace levels.
- 🔑 Hydroquinone is banned in European cosmetics. That does not mean it does not exist or does not work: it remains one of the best-supported treatments, but as a medicine and on prescription. It is the boundary between the cosmetic and the medicine.
- The timescales are long. Pigment takes months to lighten, and anyone promising results in a fortnight is promising something they cannot demonstrate.
- 🚨 Melasma has rules of its own and is not handled like a sun spot. It has its own page.
It is worth starting with what no box says: before treating pigmentation you have to know what it is. Not all brown marks are the same thing, and some respond to a cream, others need something else and a few have to be looked into before you touch them.
That said, over-the-counter depigmenting agents do do something, and they do different things from one another. This page explains where each one acts, what limits European law puts on them — two are capped and one is flatly banned in cosmetics — and why, without daily sun protection, they are all working against the current.
It is part of the dermocosmetics guide. The diagnosis of each type of pigmentation and its treatment with light are on the pages linked further down.
Would you rather we told you straight away what suits you? Eight questions, without leaving any personal data, and we send you back the complete routine.
First of all: what kind of pigmentation is it
This section is not a formality. A depigmenting cream is bought online, without anyone looking at the skin, and that is exactly the scenario that gives cause for concern.
Under the generic name of “pigmentation” live some very different things:
- Solar lentigines, the accumulated damage from the sun. They are the ones that respond best to pulsed light.
- Melasma, hormonal in origin and made worse by the sun and by visible light. It behaves the opposite way to the above and can get worse with aggressive treatments.
- Post-inflammatory hyperpigmentation, the mark left by a spot, a wound or a burn.
- And lesions that have to be looked into before you touch them. Anything that changes colour, size, shape or border, or that bleeds or itches.
🚨 No depigmenting agent should be applied to an undiagnosed lesion, and no cream makes a problem disappear that was not pigmentation in the first place. The detail of what each one is and how they are told apart is in pulsed light for sun spots, and melasma has a page of its own in why melasma comes back.
Where each active works
The skin makes melanin along a chain with several links, and each family of actives steps into a different one. Understanding that explains why combining mechanisms works better than raising the dose of just one.
| Link | What happens there | What acts on it |
|---|---|---|
| The stimulus | Sun, visible light, inflammation, hormones | Sun protection |
| The tyrosinase enzyme | The step that makes the pigment | Arbutin, kojic acid, vitamin C |
| Transfer | The pigment passes into the skin cells | Niacinamide |
| Turnover | The skin renews itself and carries the pigment away | Retinoids, exfoliants |
🔑 Look at the first row. It is the only one that acts on the cause; all the others work on the consequences. That is why a depigmenting agent without daily sun protection is bailing out the boat with the hole still open — and why the cheapest step in the routine is the one that decides whether the rest is any use. It is in how to choose a facial sunscreen.
The evidence, active by active
Here is what almost no page in this field puts side by side: what study backs each depigmenting agent, with what design and with how many people. Ordered from most to least comparative evidence.
| Active | Best available evidence | What it found |
|---|---|---|
| Cysteamine 5% | Meta-analysis of 7 randomised trials (2024) | Better than placebo (SMD −0.84; 95% CI −1.19 to −0.49) and no significant difference against 4% hydroquinone (SMD 0.16; CI −0.22 to 0.53) |
| Azelaic acid | Systematic review of 43 trials, 7 of them in melasma (2023) | At 20% it was significantly better than the vehicle, and better than 2% hydroquinone on global improvement |
| Tranexamic acid | Meta-analysis of 22 studies and 1,280 patients (2024) | It reduces the MASI. Oral > injected > topical, in that order |
| Niacinamide 5% | Double-blind trial with half-face application, 50 women, 12 weeks | It reduced hyperpigmented spots, as well as fine lines, redness and yellowing |
| Vitamin C 5% | Double-blind trial against excipient, 6 months | Improvement in tone and microrelief. Its effect is on evenness, not on established pigmentation |
| Retinoids | Authorised indication for tretinoin | It expressly includes mottled hyperpigmentation |
| Alpha-arbutin 5% + kojic 2% | Comparative study, 30 patients (2025) | No difference against the triple formula with hydroquinone, with fewer adverse effects and less recurrence |
And now the small print, which matters a great deal here
- 🚨 The arbutin-plus-kojic formula in that study cannot be sold in Europe, and that has to be said. It used 5% alpha-arbutin and 2% kojic acid, and Regulation (EU) 2024/996 limits alpha-arbutin to 2% in facial cream and kojic acid to 1% in facial and hand products. In other words: the trial used double the legal cap on both actives. A compliant European product does not reproduce that formula, so its result does not carry over to what is bought here. It is the same problem as with the retinol concentrations in the older trials.
- ⚠️ “No significant difference” does not always mean “just as good”. In small studies it can mean there was no statistical power to detect the difference. Cysteamine holds up well because it is seven trials with zero heterogeneity against placebo; the arbutin-plus-kojic figure comes from thirty patients, and with thirty patients almost nothing comes out significant.
- ⚠️ The evidence for arbutin in humans is scant, and that is worth saying: there are few studies, almost always in combination with other actives, which makes it hard to attribute the result to arbutin itself. It is not that it does not work: it is that it has not been well measured on its own.
- 🔑 The comparator in almost all these studies is hydroquinone, which is the benchmark the whole field is measured against. And hydroquinone cannot be sold in a cosmetic in Europe — hence the next section.
- ⚠️ Almost all of this evidence has been generated in melasma, which is the most studied and the most difficult pigment problem. Transferring it wholesale to a solar lentigo or a post-inflammatory mark is exactly the error of taking a figure out of its context.
What you buy, what you are prescribed and what is used off-label
This is the map that puts everything above in order, and it is the one no shop publishes — because the two depigmenting agents with the best comparative evidence are not cosmetics.
| What it is | Examples | |
|---|---|---|
| Cosmetic | Bought without a prescription. Subject to the European Regulation and its caps | Niacinamide, vitamin C, alpha-arbutin 2%, arbutin 7%, kojic acid 1%, cysteamine, retinol (0.3%) |
| Medicine | Prescribed and supervised by a doctor | Hydroquinone (banned in cosmetics), tretinoin, azelaic acid at medicine-strength concentration |
| Medicine used off-label | Authorised for something else, used here on medical judgement | Oral tranexamic acid |
Three points make that table usable:
- 🔑 Cysteamine is the interesting exception. It is the only active in the first column with a meta-analysis that finds no significant difference against 4% hydroquinone — that is, with evidence comparable to a medicine while being a cosmetic. Its practical reputation is that it smells bad, which has a considerable bearing on whether people stick with it.
- ⚠️ Azelaic acid plays in both columns. In Spain it exists as a medicine — a 15% gel, for example — but its authorised indications are papulopustular acne and papulopustular rosacea, not melasma. Its use for pigment also goes through medical judgement.
- 🚨 Oral tranexamic acid is the most delicate case, and that is why it is in a box of its own. It is the one that reduces the MASI most in the meta-analysis, and in its Spanish summary of product characteristics melasma appears nowhere at all: it is authorised for haemorrhage. The summary also warns that thromboembolic risk factors must be investigated before using it and that it should be given with care to anyone taking oral contraceptives, because of the increased risk of thrombosis. It is not an over-the-counter product nor a decision to take off a shelf, and this page gives no regimens: it is named because it is what appears in the evidence, and because anyone searching for “what works for pigmentation” deserves to know where it sits.
What European law says about depigmenting agents
Here is the information almost nobody gives the consumer, and which also explains why labels changed in 2025.
Hydroquinone is banned in cosmetics
It appears in Annex II of the European Cosmetics Regulation, entry 1339 — that is, in the list of prohibited substances. The only exception, set out separately in Annex III, is professional use in artificial nail systems up to 0.02% in the finished product. In a facial cream, no.
🔑 And now the nuance that changes everything, because it causes a great deal of confusion: the fact that it is banned in cosmetics does not mean it does not exist or does not work. Quite the opposite: in the most complete review of the evidence on melasma, combined topical treatment and hydroquinone itself remain the most effective. What happens is that it sits in the other box in law: it is handled as a medicine, prescribed and supervised by a doctor, and cannot be bought in an over-the-counter cosmetic.
It is the clearest example of the boundary described in the dermocosmetics guide: there is no third, intermediate category.
⚠️ A practical and safety consequence, with a documented case in Spain. In 2011 the Spanish Agency of Medicines and Medical Devices ordered the withdrawal of twelve depigmenting products containing hydroquinone that were being sold outside the pharmacy channel, without having gone through prior assessment or authorisation. The reason, in its own words, is that carrying that active substance gives them “the legal status of a medicine” — and the Agency recalled that hydroquinone “may produce adverse effects (irritation, hyperpigmentation and ochronosis in prolonged treatment, leucoderma…)” and that it may require prescription and medical supervision.
🔑 How this translates at the moment of buying: if a product is sold as a cosmetic and promises results proper to a hydroquinone, either it is not going to deliver them, or it should not be on sale as a cosmetic. Depigmenting agents are, alongside slimming products, the category where undeclared substances turn up most — and buying through a channel that answers for traceability is not an excessive precaution.
Arbutin has been capped since 2025
The same regulation that limited retinol — Regulation (EU) 2024/996 — also restricted these actives:
| Substance | Maximum | Where |
|---|---|---|
| Alpha-arbutin | 2% in facial creams · 0.5% in body lotions | Annex III, entry 377 |
| Arbutin | 7% in facial creams | Annex III, entry 378 |
| Kojic acid | 1%, as a skin-lightening agent, in facial and hand products | same regulation |
🔑 The cap on kojic acid is the least known and the one that most changes what can be bought. Until this regulation, kojic acid was not governed by the Cosmetics Regulation; now it is. The European scientific committee concluded, in its opinion of March 2022, that it is safe as a skin-lightening agent up to 1%, and that became the limit. Formulations from other markets with 2, 3 or 4% kojic acid are not compliant here.
The dates: non-compliant products cannot be placed on the Union market from 1 February 2025, nor made available from 1 November 2025.
🔑 And the reason connects the two halves of this section. The rule also requires that, in formulations carrying these substances, hydroquinone be kept at the lowest possible level, not exceeding unavoidable traces. The European scientific committee assessed precisely the combined exposure to hydroquinone alongside these depigmenting agents. In other words: the cap on arbutin is not an arbitrary figure, it has to do with the substance that is banned.
How long they take and what to expect
- Nothing visible in the first few weeks. Pigment already deposited needs the skin to renew itself.
- The measurements in the trials are taken at 12 weeks or more. The niacinamide one at 12; those for vitamin C and retinol at six months.
- The improvement is usually partial. Lightening is not erasing, and well-established pigmentation rarely disappears with a topical alone.
- 🚨 And it comes back if the stimulus comes back. This is not a failure of the treatment: it is how pigment works. Without sustained sun protection, each summer undoes the year’s work.
What is offered here, and in what order
🔑 There is a depigmenting compounded formulation of our own, which the medical team can prescribe after an assessment. It is not an over-the-counter cosmetic: it is a prepared formulation, and that is why it goes through the consulting room.
And the order we work in is this:
- First, the conservative regimen. Creams, used consistently and with sun protection, for long enough to be able to judge whether they work.
- If after that time the pigmentation has not shifted, we move up a step: laser, pulsed light and the other options that work on pigment already deposited.
⚠️ With one important exception, worth stating so as not to waste months: there is pigmentation that needs more aggressive treatment from the outset. Not all of it deserves six months of cream before anything else is considered. Which case is which is decided by looking at it, and that is exactly why the first question on this page was what kind of pigmentation it is.
🔑 Read alongside the above and the whole logic becomes clear: the cream is the first step because it is the cheapest and the least aggressive, not because it is always the right one.
When a cream is not enough: if after several months of consistent treatment and good sun protection the pigmentation is unchanged, the next step is not a more expensive cream. It is an assessment to decide whether pulsed light, a peel in the consulting room or medical treatment is what is called for. The options are in intense pulsed light and chemical peel.
The depigmenting agents in the catalogue are in the pigmentation shop. Which one is right depends on what kind of pigmentation it is, and that is what is determined in the consulting room — not on a label.
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Frequently asked questions
What cream removes facial pigmentation?
None “removes” it on its own, and it depends on what kind of pigmentation it is. What cosmetic depigmenting agents do do is slow pigment production and help lighten it over time, provided they are combined with daily sun protection. Without that, the result is very poor however good the product.
Can I buy hydroquinone without a prescription?
Not in a cosmetic: it is on the list of prohibited substances in the European Cosmetics Regulation. It still exists in the sphere of medicines, prescribed and supervised by a doctor. If you see an over-the-counter product containing it, or promising the same thing, be wary of the channel.
Is arbutin “natural hydroquinone”?
It is a related precursor, and that is precisely why the European regulator took an interest in it: it set a concentration cap and required that any hydroquinone present in the formulation be kept at unavoidable trace levels. Arbutin within those limits is a permitted active; the nuance is that its regulation exists because of that relationship.
How long before anything shows?
Months, not weeks. The measurements in the trials are taken at 12 weeks in the case of niacinamide and at six months for vitamin C. It is a treatment of persistence, and the persistence that counts most is with the sunscreen.
Do they work for melasma?
Melasma is something else and has rules of its own: it is hormonal, it is made worse by the sun and by visible light, and it can get worse with aggressive treatments. What the evidence says about it is in why melasma comes back, what really works and when pulsed light is not the answer.
Which depigmenting agent works best?
It depends on what kind of pigmentation it is and on which legal box you are willing to move in. Of those bought without a prescription, the one with the best comparative evidence is 5% cysteamine: a meta-analysis of seven trials found no significant difference against 4% hydroquinone. Its practical drawback is the smell, which makes a lot of people give up on it. Above that are options that are already medicines and are prescribed by a doctor.
I have read that tranexamic acid works very well — should I buy it?
It is the one that reduces the melasma index most in the available meta-analysis, taken orally — and that is where the problem lies. In Spain oral tranexamic acid is a medicine whose authorised indications are haemorrhage: melasma does not appear in its summary of product characteristics. Its use for pigment is off-label, and the summary itself requires thromboembolic risk factors to be investigated before it is used and warns of the risk of thrombosis in anyone taking oral contraceptives. It is not a decision to take off a shelf. Topical formulations do exist in cosmetics, and those are the ones that performed least well in the meta-analysis.
And pigmentation on the hands?
It responds to the same principles, with two practical differences: hands are washed constantly, so the product does not last as long, and almost nobody puts sunscreen on them, even though they are among the most exposed areas of the body. They usually need more persistence than the face.
My pigmentation has darkened with the treatment — what do I do?
Stop and get it looked at. It may be a reaction to a product that was too aggressive, added post-inflammatory hyperpigmentation, or the lesion may not have been what it was thought to be. In none of those three cases is the answer to persist.
Sources
- Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. Text in the BOE. — The framework regulation. Annex II is the list of substances prohibited in cosmetic products and Annex III that of restricted substances. Hydroquinone appears in Annex II at entry 1339, with the sole exception — set out in Annex III — of professional use in artificial nail systems. ✅ Verified on 28-08-2026 against the consolidated text on EUR-Lex; the entry reads verbatim: “1339 — 1,4-Dihydroxybenzene (Hydroquinone), except entry 14 of Annex III”, CAS 123-31-9, EC 204-617-8, within the “List of substances prohibited in cosmetic products”. On 27-08 the entry number carried a reservation because the BOE does not display the annexes; that reservation is now lifted.
- AEMPS. Information notice: withdrawal of certain products containing hydroquinone (20 July 2011). aemps.gob.es. — Withdrawal of twelve depigmenting products containing hydroquinone that were being marketed outside the pharmacy channel, without pre-marketing assessment or authorisation. Containing that active substance gives them “the legal status of a medicine”. The Agency warns that hydroquinone “may produce adverse effects (irritation, hyperpigmentation and ochronosis in prolonged treatment, leucoderma…)” and that it may require prescription and supervision by a doctor. ⚠️ A 2011 notice: it is cited as a documented Spanish case of the cosmetic–medicine boundary, not as a current alert about specific products.
- Commission Regulation (EU) 2024/996 of 3 April 2024 amending Regulation (EC) No 1223/2009 as regards the use of vitamin A, Alpha-Arbutin and Arbutin and certain substances with potential endocrine-disrupting properties. Text in the BOE. — Annex III, entry 377 (alpha-arbutin): 2% in facial creams and 0.5% in body lotions. Entry 378 (arbutin): 7% in facial creams. Formulations containing them must keep hydroquinone at the lowest possible level, not exceeding unavoidable traces. And kojic acid: maximum 1%, as a skin-lightening agent, in facial and hand products — recitals 8 and 14 of the regulation itself, which state that kojic acid “is not regulated by Regulation (EC) No 1223/2009” before this amendment and record the SCCS opinion of 15-16 March 2022 finding it safe up to that concentration. Kojic acid verified against the EUR-Lex text on 28-08-2026. Dates of application: 1 February 2025 for placing on the market and 1 November 2025 for making available. Scientific basis: opinion of the Scientific Committee on Consumer Safety of 31 January 2023, which assessed the combined exposure to hydroquinone and these depigmenting agents. Verified against the official text on 27-08-2026.
- Mawu FO, Christopher PM. Efficacy and safety of cysteamine 5% cream for the management of melasma: a systematic review and meta-analysis of randomized controlled trials. Archives of Dermatological Research, 2024. PMID 39673630. — Meta-analysis of 7 randomised trials using random-effects models. Cysteamine 5% was more effective than placebo at reducing the melasma area and severity index (standardised mean difference −0.84; 95% CI −1.19 to −0.49; p < 0.00001; I² = 0%) and showed no significant difference against 4% hydroquinone (SMD 0.16; 95% CI −0.22 to 0.53; p = 0.42; I² = 55%). Adverse effects (erythema, irritation, burning, itching, dryness) were more frequent than with placebo and similar to those of hydroquinone.
- King S, Campbell J, Rowe R, Daly ML, Moncrieff G, Maybury C. A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging. Journal of Cosmetic Dermatology, 2023. PMID 37550898. — Systematic review of 43 randomised trials, of which 7 in melasma: azelaic acid 20% was significantly better than the vehicle on severity and global improvement, and better than 2% hydroquinone on global improvement.
- Calacattawi R, et al. Tranexamic acid as therapeutic option for melasma management. Journal of Dermatological Treatment, 2024. PMID 38843906. — Meta-analysis of 22 studies and 1,280 patients distinguishing the three routes: the oral route showed the greatest reduction in MASI, followed by the injected and the topical. Adverse effects reported: gastrointestinal discomfort, skin irritation and menstrual irregularities.
- Tantanasrigul P, Sripha A, Chongmelaxme B. The efficacy of topical cosmetic containing alpha-arbutin 5% and kojic acid 2% compared with triple combination cream for the treatment of melasma. Journal of Cosmetic Dermatology, 2025. PMID 39555866. — Prospective comparative study in 30 patients: no statistical difference in mMASI or melanin index against the triple formula (hydroquinone, tretinoin and corticosteroid), with fewer adverse effects and less recurrence in the arbutin and kojic group. ⚠️ Small sample: the absence of a difference is not the same as demonstrated equivalence.
- AEMPS — CIMA. Summary of product characteristics for Finacea 150 mg/g gel (azelaic acid). cima.aemps.es. — A medicine with 150 mg (15%) of azelaic acid per gram. Authorised indications: relief of mild to moderate papulopustular acne of the facial area and topical treatment of papulopustular rosacea. Most frequent adverse reactions: pruritus, burning and pain at the application site. ⚠️ Melasma is not among its authorised indications.
- AEMPS — CIMA. Summary of product characteristics for Amchafibrin 500 mg tablets (tranexamic acid). cima.aemps.es. — Authorised indications: treatment and prophylaxis of haemorrhage associated with excessive fibrinolysis (prostate or bladder surgery, menorrhagia, haemophilia with dental surgery, hereditary angioneurotic oedema). 🚨 Melasma appears nowhere in the summary. It also warns that “the risk factors for thromboembolic disease must be investigated before using tranexamic acid” and that “it must be administered with care in patients receiving oral contraceptives owing to the increased risk of thrombosis”. Verified on 27-08-2026.
- McKesey J, Tovar-Garza A, Pandya AG. Melasma Treatment: An Evidence-Based Review. American Journal of Clinical Dermatology, 2020;21(2):173-225. PMID 31802394. — A review of 113 studies and 6,897 participants: combined topical treatment and hydroquinone remain the most effective; laser and light devices give mixed results, equal to or worse than topicals and with a greater risk of adverse effects. A source shared with the site’s melasma page; the framing has been checked so that both say the same thing.
- Bissett DL, Oblong JE, Berge CA. Niacinamide: a B vitamin that improves aging facial skin appearance. Dermatologic Surgery, 2005;31(7 Pt 2). PMID 16029679. — Double-blind trial with application to half the face and vehicle on the other, twice daily for 12 weeks in 50 women with facial photoageing: a reduction in hyperpigmented spots, fine lines and wrinkles, redness and yellowing, with improved elasticity.
- Humbert PG, Haftek M, Creidi P, et al. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Experimental Dermatology, 2003;12(3). PMID 12823436. — Vitamin C 5% for six months on the neck and arms, double-blind against excipient. The reference for this active’s measurement window.
- AEMPS — CIMA. Summary of product characteristics for Retirides 0.5 mg/g cream (tretinoin). cima.aemps.es. — Among its authorised indications is, as adjuvant treatment, the reduction of mottled hyperpigmentation of facial skin. A prescription-only medicine.
- Hughes MC, Williams GM, Baker P, Green AC. Sunscreen and prevention of skin aging: a randomized trial. Annals of Internal Medicine, 2013;158(11). PMID 23732711. — Randomised trial in 903 adults followed for 4.5 years: 24% less skin ageing with daily sunscreen use. It underpins the priority of sun protection over the rest of the routine.
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If you have spent months on a depigmenting cream and the pigmentation is unchanged, the most useful thing is not to switch product: it is to know what kind of pigmentation it is. Everything else depends on that — some responds well to a topical, some needs light and some has to be looked into before it is treated. It is a short assessment and it saves months of the wrong treatment.
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Last reviewed: 17 September 2026. This content is for information only and does not replace an individual assessment by a healthcare professional.
