Systematic review of randomized controlled trials on interventions for melasma: An abridged Cochrane review

Background: Multiple treatments exist for melasma; they are often substandard and associated with side effects. Objectives: We sought to assess the effectiveness of interventions used in the management of all types of melasma. Methods: We undertook a systematic review using the methodology of the Cochrane Collaboration. Results: We included 20 studies with a total of 2125 participants covering 23 different treatments. A meta-analysis was not possible because of the heterogeneity of treatments. Triple-combination cream (hydroquinone, tretinoin, and fluocinolone acetonide) was more effective at lightening melasma than hydroquinone alone (relative risk 1.58, 95% confidence interval 1.26-1.97) or any of the agents in a dual-combination cream. Azelaic acid (20%) was significantly more effective than 2% hydroquinone (relative risk 1.25, 95% confidence interval 1.06-1.48) at lightening melasma. In 2 studies where tretinoin was compared with placebo, objective measures demonstrated significant reductions in the severity. However, only in 1 study did participants rate a significant improvement (relative risk 13, 95% confidence interval 1.88-89.74). Limitations: There was poor methodology, a lack of standardized outcome assessments, and short duration of studies. Conclusions: The current limited evidence supports the efficacy of multiple interventions. Randomized controlled trials on well-defined participants with long-term outcomes are needed.