Background: Postinflammatory hyperpigmentation (PIH) is the most common adverse effect following laser treatments, yet the relative efficacy of proposed prophylactic measures remains uncertain.
Objectives: To compare the effectiveness of available interventions for preventing laser-induced PIH in randomized controlled trials (RCTs).
Methods: PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov were searched through February 2025. RCTs reporting PIH incidence after laser or other energy-based treatments were eligible. A random-effects network meta-analysis (NMA) combined direct and indirect evidence; treatments were ranked by surface under the cumulative ranking curve (SUCRA).
Results: Fourteen RCTs were included in the systematic review, with 11 included in the NMA. Intradermal tranexamic acid (TXA), topical corticosteroids, topical vasoconstrictors, oral TXA, and epidermal cooling were significantly more effective in reducing PIH incidence compared with sunscreen monotherapy, with intradermal TXA demonstrating the highest efficacy (RR: 0.02, 95% CI: 0.00-0.53). Whitening agents and epidermal growth factor formulations did not show significant benefit over sunscreen, while sunscreen monotherapy was ineffective compared with placebo. Reported adverse events were generally mild, although intradermal TXA was associated with injection site discomfort and bruising.
Conclusion: This systematic review and NMA indicate that topical corticosteroids and intradermal TXA may offer greater protection against laser-induced PIH than sunscreen monotherapy. Preventive strategies should be incorporated into laser treatment planning, particularly for patients with higher risk of hyperpigmentation. Overall, the findings support an evidence-based and individualized approach to PIH prevention. Interpretation should remain cautious due to the limited number and modest sample sizes of included trials.