Blue Photosensitizer, Red Light, Clear Results: An Integrative Review of the Adjunctive Periodontal Treatment with Methylene Blue in Antimicrobial Photodynamic Therapy

The adjunctive use of antimicrobial photodynamic therapy (aPDT) has been investigated as a promising approach to enhance periodontal therapy. Methylene blue (MB) is the most commonly used photosensitizer due to its favorable characteristics, including a neutral pH and an absorption peak at 660 nm. Due to the considerable heterogeneity among studies and the lack of well-established clinical protocols, this study aims to conduct an integrative review to highlight the effects of MB-mediated aPDT as an adjunct to periodontal treatment. The inclusion criteria were randomized clinical trials that used MB as the PS, published between 2009 and 2024, with a minimum follow-up of three months. Studies included patients with periodontitis treated with SRP alone or in combination with aPDT. Of the 237 studies initially identified, 23 met the eligibility criteria and were included in this integrative review. The risk of bias was evaluated using the Cochrane criteria for randomized controlled trials. Although the included studies reported heterogeneous clinical outcomes, a general trend toward improvement in key periodontal parameters-probing depth, bleeding on probing, clinical attachment level, and plaque index-was observed when MB-mediated aPDT was used as an adjunct to conventional periodontal treatment. However, substantial variability in clinical protocols-including differences in photosensitizer concentration, type of light source, irradiation time, and frequency of application-limited the comparability of results across studies. Despite these methodological inconsistencies, current evidence suggests that MB-mediated aPDT holds promise as an adjunctive approach in periodontal therapy. Nevertheless, due to the clinical heterogeneity and the limited number of studies with long-term follow-up, its overall efficacy remains inconclusive. Further well-designed randomized controlled trials with standardized protocols and subgroup analyses are essential to validate its clinical relevance.