A Randomized, Double-Blind, Split-Face Study of Topical Silymarin vs 2% Hydroquinone Cream in Melasmas

Background: Hydroquinone is effective in melasma treatment, but side effects may limit its use. Silymarin cream may be a safer alternative. Objective: To compare the efficacy of 1.4% silymarin with 2% hydroquinone for melasma treatment in Asians. Methods: In a randomized, double-blind, split-face study of 25 patients with epidermal or mixed-type melasma, the facial sides were randomized for the application of silymarin cream on one side and hydroquinone on the contralateral side for 3 months. Results were evaluated using a colorimeter, modified Melasma Area and Severity Index (mMASI) score, and patient self-assessment. Results: Twenty-three patients completed the study. Colorimetric measurements calculated as relative lightness index (RL*I) showed no statistical difference between the 2 treatments (P=0.715). Compared with baseline, both treatments showed statistically significant improvements of RL*I, with 14.56% and 12.82% improvement in silymarin and hydroquinone, respectively. Modified MASI scores decreased after both treatments but were only statistically significant on the hydroquinone side, achieving 17.97% reduction (P=0.02) vs 7.11% (P=0.32) on the silymarin side. There was no statistically significant difference of the RL*I and modified MASI between the 2 treatments (P>0.05). Patients’ assessment of hydroquinone treatment showed a 69.6% good-excellent improvement with a visual analog scale (VAS) satisfaction score of 7.82, compared with silymarin showing a 73.9 % good-excellent improvement and VAS score of 7.65 (P=0.50). More adverse effects occurred with the hydroquinone. Conclusion: Although hydroquinone showed a better response, topical silymarin was effective in the treatment of epidermal and mixed-type melasma with fewer side effects.