What is the recommended treatment regimen for melasma, including first‑line topical therapy, alternatives for hydroquinone contraindications, and adjunctive procedures?

Melasma Treatment

Start with triple combination cream (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) applied nightly combined with strict broad-spectrum SPF 50+ sunscreen reapplied every 2-3 hours, and if inadequate response after 8-12 weeks, add intradermal platelet-rich plasma (PRP) injections every 2-3 weeks for 4 sessions. 1, 2

First-Line Topical Therapy

Triple combination cream is the most effective topical treatment for melasma. 3, 4 This formulation contains:

• Hydroquinone 4% (melanin synthesis inhibitor) 1, 5
• Tretinoin 0.05% (increases epidermal turnover and enhances hydroquinone penetration) 1, 4
• Fluocinolone acetonide 0.01% (reduces inflammation and irritation while enhancing penetration) 1, 4

Apply once daily at bedtime to affected areas. 1

Alternative First-Line Options When Triple Combination Is Contraindicated

If patients cannot tolerate triple combination or it is unavailable:

• Hydroquinone 4% monotherapy remains highly effective 3, 5, 4
• Dual therapy with hydroquinone plus glycolic acid 4
• Azelaic acid 20% as a single agent 4
• Tretinoin 0.1% alone 4

Microencapsulated hydroquinone 4% with retinol 0.15% and antioxidants offers comparable efficacy to triple combination with potentially better tolerability for long-term use. 5

Mandatory Photoprotection (Foundation of All Treatment)

Sun protection is non-negotiable and must be maintained throughout treatment and indefinitely for maintenance. 1, 3, 6

Specific Photoprotection Requirements:

• Apply broad-spectrum SPF 50+ sunscreen (minimum SPF 30) 1
• Reapply every 2-3 hours during outdoor exposure, and immediately after swimming or sweating 1
• Wear wide-brimmed hats (>3-inch brim) when outdoors 1
• Seek shade during peak UV hours (10 a.m. to 4 p.m.) 1
• Use UV-protective clothing with tight weave fabrics and darker colors 1
• Avoid tanning beds and sunlamps completely 1

Common pitfall: Patients frequently forget to reapply sunscreen after 2-3 hours or following water exposure, which undermines all other treatments. 1

Second-Line Treatment: Intradermal PRP Injections

If topical therapy shows inadequate response after 8-12 weeks, add intradermal PRP injections—the most effective advanced treatment for melasma. 1, 2, 7

PRP Treatment Protocol:

• Administer 4 treatment sessions spaced every 2-3 weeks 1, 2
• Inject intradermally at 1 cm intervals across all affected areas 1
• Apply topical anesthetic 30 minutes before the procedure 1
• Ensure adequate skin lubrication with topical agent or PRP during needling 1
• Follow-up evaluation one month after the final treatment 1
• Maintenance treatments every 6 months due to melasma's chronic relapsing nature 1, 7

PRP demonstrates significantly superior efficacy compared to intradermal tranexamic acid injections (mean mMASI reduction 53.66% with PRP-TXA combination vs. lower with TXA alone), with similar side effect profiles and higher patient satisfaction rates exceeding 90%. 1, 2, 7

Significant improvement is typically visible within 6 weeks as measured by modified Melasma Area and Severity Index (mMASI) scores. 1, 2, 7

Adjunctive Oral Therapy

Consider oral tranexamic acid 250 mg twice daily, particularly when combined with PRP injections. 1, 7

• PRP combined with oral tranexamic acid shows higher total efficacy (90.48%) compared to tranexamic acid alone (73.68%) 1, 7
• Lower disease recurrence rates with combination therapy 1, 7
• Oral tranexamic acid is more effective than topical tranexamic acid for hyperpigmentation 2
• Promising for moderate to severe recurrent melasma 3

Caveat: More long-term safety data are needed, though current evidence shows mild adverse events primarily consisting of skin irritation, dryness, and erythema. 3

Alternative Procedural Options

Microneedling

Microneedling may be more effective than intradermal PRP injections in some patients and should be considered if PRP is unavailable or ineffective. 1, 7

Microneedling protocol:

• Needle depth 0.25-2.5 mm depending on treatment area 1
• Very low risk of post-inflammatory hyperpigmentation in Fitzpatrick III-VI skin types 1
• Minimal downtime (24-48 hours) 1
• Safe for all skin types including thin, sensitive, and ethnic skin 1
• Apply topical anesthetic 30 minutes before treatment 1
• Avoid sun exposure for 24 hours post-procedure 1
• Avoid fragranced products for 24 hours after treatment 1
• Do not treat over tattoos or permanent makeup 1

For radiofrequency microneedling specifically: three treatment sessions spaced at least 21 days apart, with maintenance every 6 months. 7

Chemical Peels

Chemical peels show mixed results and are equal or inferior to topical therapies with a higher risk of adverse effects. 3 Consider only in patients who have failed first-line topical therapy, either alone or combined with topicals. 4

Laser and Light-Based Devices

Laser therapy should rarely be used for melasma and carries significant risks. 4

Critical warning for darker skin types (Fitzpatrick IV-VI): Laser therapy is associated with markedly higher risk of burns, post-inflammatory hyperpigmentation, and hypopigmentation due to increased melanin absorption of laser energy; it should be avoided or employed only with extreme caution and thorough patient counseling. 1

Laser and light-based devices show mixed results and are equal or inferior to topical therapies with higher adverse event rates. 3

Measuring Treatment Success

Use standardized mMASI scores to objectively track improvement: 1, 7

• MASI decrease >60-90% = moderate improvement 1
• MASI decrease >90% = excellent response 1
• Patient satisfaction assessment should complement objective measurements 1, 7

Treatment Algorithm

1. Initiate triple combination cream nightly + SPF 50+ sunscreen reapplied every 2-3 hours 1, 4
2. Assess response at 8-12 weeks 2
3. If inadequate response: Add intradermal PRP injections every 2-3 weeks for 4 sessions 1, 2
4. Consider adding oral tranexamic acid 250 mg twice daily for enhanced efficacy 1, 7
5. Maintenance phase: Continue sun protection, intermittent topical therapy, and PRP maintenance every 6 months 1, 2

Critical Pitfalls to Avoid

• Discontinuing treatment prematurely—melasma is a chronic condition requiring long-term maintenance therapy; recurrence rates are high without ongoing treatment 1, 2, 7
• Inadequate sunscreen reapplication—forgetting to reapply after swimming, sweating, or every 2-3 hours undermines all other interventions 1
• Using laser therapy in darker skin types (Fitzpatrick IV-VI) without extreme caution due to high risk of pigmentary complications 1, 4
• Failing to address hormonal influences—pregnancy, oral contraceptives, and hormone replacement therapy may limit treatment success, though women may continue these agents when medically indicated 1, 7
• Patient smoking—counsel patients to avoid smoking, which can worsen melasma 1, 7