Periodontal infections tend to be site-specific, mostly confined to the periodontal pocket. With the surge of antibiotic-resistant bacteria, the trend is shifting towards other therapeutic modalities, especially locally delivered approaches that include other pharmacotherapeutic drugs and medical devices. This narrative review aimed to provide insights into the clinical efficacy of local drug delivery and adjunctive agents used in nonsurgical management of periodontitis. Electronic (PubMed/MEDLINE, CENTRAL, and EMBASE) and bibliographic searches of past systematic reviews were carried out to identify previous publications on the topic. Only relevant literature and randomized controlled trials published in English were selected. In addition, a literature review was developed based on the selected articles. Experimental drugs or agents were excluded. This review highlights the clinically proven and commercially available therapeutic agents related to the management of periodontal disease with comparisons of their clinical efficacies and challenges. A vast array of commercial local pharmacotherapeutic agents had been clinically tested, but the methodologies and clinical results varied within and between each agent used, causing difficulty in drawing conclusions and providing support to the superiority of one agent over another. Considering the benefit–cost ratio with the modest clinical results, the long-term usefulness of these agents remains debatable.

The aim of this systematic review is to compare the clinical efficacy of repeated applications of local drug delivery and adjunctive agents (LDAs) in nonsurgical periodontal therapy (NSPT) compared to subgingival mechanical debridement (SMD) alone. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, Web of Science, hand-searched literature and grey literature databases were searched for randomized controlled clinical trials (RCTs) with a minimum of 6-month follow-up. The outcomes of interest were changes in probing pocket depth and clinical attachment level as well as patient-centred outcomes. Of 1094 studies identified, 16 RCTs were included in the qualitative analysis. Across 11 different adjuncts analysed, only two studies utilizing minocycline gel/ointment and antimicrobial photodynamic therapy (aPDT) with indocyanine green photosensitizer had statistically significant differences in primary outcomes when compared to their control groups. Only one study on aPDT methylene blue 0.005% had compared single versus multiple applications against its control group. A mean range of 0.27–3.82 mm PD reduction and −0.09–2.82 mm CAL gain were observed with repeated LDA application. Considerable clinical heterogeneity and methodological flaws in the included studies preclude any definitive conclusions regarding the clinical efficacy of repeated LDA applications. Future RCTs with a direct comparison between single and repeated applications should be conducted to confirm or refute the clinical advantages of repeated LDA application in the nonsurgical management of periodontitis.

This review aimed to rank the clinical efficacy of commercially available single-application local drug delivery and adjunctive agents (LDAs) compared with subgingival mechanical debridement (SMD) in nonsurgical periodontal therapy (NSPT). Randomized controlled clinical trials that compared LDAs against SMD alone or with placebo in adults (aged at least 18 years) diagnosed with periodontitis with a minimum of 6 months follow-up were included. A frequentist approach to random-effects network meta-analysis was implemented. The efficacies of the LDAs measured by probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain were reported as mean difference (MD) with 95% confidence intervals (CIs). The treatments were ranked according to their P-score. Four network meta-analyses suggested that sulfonic/sulfuric acid gel (PPD MD −1.13 mm, 95% CI −1.74 to −0.53, P-score 0.91; CAL MD −1.09 mm, 95% CI −1.58 to −0.61, P-score 0.95) and doxycycline hyclate gel (PPD MD −0.90 mm, 95% CI −1.50 to −0.30, P-score 0.93; CAL MD −0.84 mm, 95% CI −1.40 to −0.28, P-score 0.92) were the most effective in reducing PPD and gaining CAL in split-mouth and parallel studies, respectively (moderate certainty of evidence). LDAs have differing efficacies, but they present with possible clinical significance over SMD alone in NSPT.