last 15 years (since January 1st, 2003) as this period was considered
clinically relevant. Clinical recommendations were based
on the American College of Physicians (ACP) guidelines.10 We
excluded studies using proprietary or undescribed active ingredients
(as these studies and outcomes would not be verifiable
or reproducible by third parties, if desired) and those evaluating
non-topical agents (ie, oral medications, bleaching agents,
chemical peels, intralesionally administered drugs, laser,
and light-based therapies) as stand-alone or combination approaches.
Patients were allowed to apply daily sunscreen in the
included studies. Non-randomized original reports, literature
reviews, conference abstracts, oral presentations, basic science
investigations, animal studies, and non-English articles were excluded.
We examined the bibliographies of included published
original reports and literature reviews to ensure that relevant
articles were included in the systematic search.
RESULTS
Our systematic search identified 9,413 articles. After screening
titles, abstracts, and full text articles, we identified 35 original
RCTs using azelaic acid (2), cysteamine (2), epidermal growth
factor (EGF) (1), liposomal hydroquinone (1), lignin peroxidase
(1), mulberry extract (1), niacinamide (1), Rumex occidentalis
(1), tranexamic acid (TXA) (5), TC therapy (5), 4-n-butylresorcinol
(3), glycolic acid (2), kojic acid (2), aloe vera (1), ascorbic acid (1),
dioic acid (1), ellagic acid and arbutin (1), flutamide (1), parsley
(1), or zinc sulfate (2) for melasma. Table 1 provides a detailed
summary of the identified studies and highlights study designs,
treatment parameters, results, and adverse events (AEs).
