Efficacy and Safety of Integrative and Complementary Treatments Versus Conventional Therapies in Patients with Vitiligo: A Systematic Review

Vitiligo is a chronic depigmenting disorder with substantial psychosocial burden. Conventional therapies (topical corticosteroids, calcineurin inhibitors, phototherapy) have variable efficacy and tolerability, prompting growing interest in integrative and complementary treatments (ICTs). To synthesize evidence on the efficacy and safety of ICTs compared with conventional therapies in vitiligo and to outline their potential role, advantages, and limitations in clinical decision-making. Data Sources and Study Eligibility We systematically searched MEDLINE (PubMed), Embase, CENTRAL, LILACS, and the ICTRP and ClinicalTrials.gov trial registries from inception to the review date for randomized and quasi-experimental comparative studies evaluating ICTs (e.g., botanicals, fire needle therapy, microneedling-assisted drug delivery) versus conventional topical treatments or placebo in patients with vitiligo. Two reviewers independently screened records, selected studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. When at least two clinically and methodologically similar trials reported comparable dichotomous outcomes, we pooled effect estimates using random-effects meta-analysis and expressed results as risk ratios (RRs) with 95% confidence intervals (CIs). Six randomized controlled trials (total n = 255) met inclusion criteria; no eligible quasi-experimental or observational comparative studies were identified. Interventions included topical turmeric cream, oral Ginkgo biloba, fire needle therapy alone or combined with tacrolimus, microneedling-assisted delivery of calcipotriol plus betamethasone versus tacrolimus, and the traditional Chinese formulation Zengse Pill. Across individual trials, several ICTs achieved statistically significant improvements in repigmentation, lesion area reduction, or disease arrest compared with placebo or active comparators. Three studies were judged at overall low risk of bias and three had some concerns, mainly regarding allocation concealment and blinding. An exploratory meta-analysis of two trials (Zengse Pill and Ginkgo biloba) yielded a nonsignificant pooled RR of 2.05 (95% CI 0.79–5.35; I² = 52.6%), reflecting imprecision and moderate heterogeneity. Adverse events were generally mild and manageable (local irritation, transient erythema/itching, occasional mild nausea), and no serious treatment-related events were reported. The evidence base is constrained by small sample sizes, short follow-up, heterogeneity of ICT protocols and outcome measures, incomplete reporting of key determinants such as Fitzpatrick phototype, and potential confounding by ambient ultraviolet exposure in predominantly tropical or subtropical study settings. Current data suggest that selected ICTs may serve as well-tolerated adjunctive options for patients with vitiligo, particularly when conventional therapies are insufficient or poorly tolerated. However, the certainty of benefit remains low due to methodological limitations and heterogeneity. Larger, multicenter randomized trials with longer follow-up and standardized outcome sets are needed before ICTs can be routinely integrated into vitiligo treatment algorithms. Registration: PROSPERO: 1141017. PRISMA 2020 guidelines were followed.