Efficacy of formulations for treating hyperpigmentation: a systematic review and meta-analysis

Abstract

Hyperpigmentation is a commonly occurring skin problem, it affects people's quality of life by causing anxiety and depression in them. This systematic review aims to critically evaluate the evidence of the effectiveness of formulations utilized in clinical trials for treating hyperpigmentation (melasma and photoaging). A comprehensive search was conducted using the Scopus, PubMed, Google Scholar, and National Center for Biotechnology Information (NCBI) databases, encompassing literature available up to December 2023. Clinical trials employing various formulations to address skin hyperpigmentation effectively were included and subsequently analysed. Meta-analysis was conducted using IBM SPSS Statistics software (version 29.0.1.0 for window) guidelines. From 102 literatures, 07 clinical studies that follow the inclusion criteria were selected. A total of 337 participants underwent a clinical trial, where 198 participants received the drug and 153 received a placebo. Meta-analysis of 07 clinical studies indicated that employed formulations have a significant effect on treating skin hyperpigmentation {Odds Ratio (OR): 4.260, 95% Confidence Interval (CI) 2.244 to 8.087, Probability value (P) p < 0.001} than placebo. Across 07 clinical trials, heterogeneity was found to be low {Tau-Squared (µ²) = 0.46, Degree of Freedom (df) = 6, p = 0.001, i-Squared (I²) = 0.76}. Formulations assessed in the meta-analysis are Ziziphus jujuba (Z. jujuba) syrup, Amorphophallus konjac (A. konjac) capsules, herbal mixture cream, cysteamine cream, 4-hexyl-1,3-phenylenediol lotion, lignin peroxidase cream, and 0.1% tretinoin cream. 0.1% tretinoin cream shows the lowest effect size while A. konjac capsules show the highest effect size among all the included studies. Formulations used in clinical trials have proven to be effective and safe for controlling skin hyperpigmentation compared to placebo treatments. Among all the formulations, 0.1% tretinoin demonstrates lower efficacy, while A. konjac exhibits the highest efficacy in treating hyperpigmentation. This systematic review will guide researchers and dermatologists in selecting quality products from the available formulations.

Keywords: Formulations; Hyperpigmentation; Melanin; Meta-analysis; Tyrosinase enzyme.