Clinical Efficacy of Single Application Local Drug Delivery and Adjunctive Agents in Nonsurgical Periodontal Therapy: A Systematic Review and Network Meta-Analysis

Abstract

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.

Effect of locally delivered adjunctive antibiotics during surgical periodontal therapy: a systematic review and meta-analysis

“…A recent systematic review evaluating the effect of locally delivered antimicrobials in conjunction with non-surgical periodontal therapy [9] reported similar improvements with locally delivered antibiotic application for CAL gain (0.263 mm, 95% CI [0.123; 0.403]) in short-term with no significantly different effects observed for longer-term follow-up (12-60 months) (0.09 mm, 95% CI [−0.253; 0.433]) and a significant POD reduction in short-(0.364 mm, 95% CI [0.236; 0.491]) and long-term (0.190 mm, 95% CI [0.059; 0.321]) follow-ups respectively. A similar systematic review further reported an average CAL gain of 0.27-0.3 mm (range between −0.56 and 1.09 mm) and POD reduction of 0.30-0.48 mm (range between −0.7 and 1.13 mm) with local drug delivery following subgingival mechanical debridement [10]. Yet, the magnitudes of the reported benefits of the locally delivered antimicrobials with non-surgical periodontal therapy for CAL gain and PPD reduction appear smaller than the currently observed results.…”

“…Reversing periodontitis-associated dysbiosis is one of the primary strategies of periodontal therapy, comprising clinical strategies, implying the improvement of patients' self-performed oral hygiene [2], in combination with professional mechanical debridement [3,4] and in selective clinical conditions the application of adjunctive antimicrobial agents, systemically [5][6][7] or locally [8,9]. Compared to systemic antibiotic application, local delivery demonstrates lower incidence of side effects, improved compliance, with lesser chances for emergence of microbial resistance [9,10].…”

Clinical Efficacy of Repeated Applications of Local Drug Delivery and Adjunctive Agents in Nonsurgical Periodontal Therapy: A Systematic Review

“…The application of local adjuncts could minimize possible adverse effects and avoid the development of antibiotics resistance from systemic antimicrobials [20]. Previous systematic reviews (SRs) on local drug delivery and adjunctive agents (LDAs) [21][22][23][24][25][26][27][28] concluded that local adjuncts have additional clinical benefits up to 1.13 mm in PD reduction and 1.09 mm in clinical attachment level (CAL) gain compared to mechanical debridement alone. Nevertheless, different adjuncts demonstrate variable clinical efficacy according to their respective mechanism of actions [8].…”

“…Nevertheless, different adjuncts demonstrate variable clinical efficacy according to their respective mechanism of actions [8]. A recent network meta-analysis (NMA) on LDAs [26] concluded that a single application of sulfonic/sulfuric acid gel and DH gel were the most effective in reducing PDs and gaining CALs in split-mouth and parallel study designs, respectively. Sulfonic/sulfuric acid gel demonstrated probable to definite clinical significance as an adjunct.…”

“…Previous SRs did not segregate the frequency of LDA application in their meta-analyses [21][22][23][24][25]27]. Furthermore, recent NMAs on the topic reported findings on single applications of LDAs so as to avoid heterogeneity in the analysis [26,29]. Repeated applications of LDAs are a valid clinical consideration in improving periodontal outcomes due to the issue of substantivity of the agents as well as the influence of elevated gingival crevicular fluid flow within the inflamed periodontal pocket [30].…”