Adjunctive Antimicrobial Photodynamic Therapy in Non-Surgical Periodontal Treatment: Clinical and Microbiological Insights from a Randomized Split-Mouth Trial

Background/Objectives: Antimicrobial photodynamic therapy (aPDT) has been proposed as an adjunct to non-surgical periodontal therapy, although its benefits remain debated. This study evaluated the clinical and microbiological effects of aPDT combined with ultrasonic scaling and root planing (US-SRP) compared with US-SRP alone in patients with periodontitis. Methods: In this randomized split-mouth clinical trial, 40 patients with stage II–III periodontitis were included. Two non-adjacent sites with probing pocket depth (PPD) ≥ 5 mm were assigned to either control (US-SRP) or test (aPDT + US-SRP) treatment. Clinical parameters, including PPD, bleeding on probing (BOP), plaque index (PI), gingival recession (REC), and clinical attachment level (CAL), were assessed at baseline and after 90 days. Subgingival plaque samples were analyzed by multiplex PCR for major periodontal pathogens. Results: No statistically significant differences were detected for microbiological outcomes at 90 days between groups. Significant greater variations were observed at T3 in the aPDT group for PPD (p = 0.04), BOP (p = 0.03) and PI (p = 0.005), whereas the control group showed a significant reduction only for PI (p = 0.01). Regarding comparisons of Δ(T0–T3) between the aPDT group and the control group, the paired t-test was significant for PPD, REC and CAL (p < 0.001), with a Cohen’s dav < 0.5 for all three parameters (small effect sizes). In addition, the aPDT group showed a statistically significant reduction in BOP (p = 0.03 *) from T0 (92%) to T3 (50%). Exploratory analyses confirmed the same trend for BOP reduction in the aPDT group both in smokers and non-smokers. Conclusions: Despite the fact that adjunctive aPDT seems to offer predictable clinical outcomes in terms of PPD and BOP reductions, further larger and stratified studies are needed to verify if this treatment can provide superior benefits compared with conventional non-surgical periodontal therapy.