The initial search resulted in 9420 articles from the MEDLINE (Ovid) and Cohrane Central Register of Controlled Trials (CENTRAL) databases. After evaluating titles and abstracts, inclusion and exclusion criteria were applied to the remaining 27 full-text articles (inter-reader agreement κ=0.85). Finally, 12 RCTs were included into the review (inter-reader agreement κ=0.96). The study selection process is presented in Figure 1.
The reasons for excluding studies after full-text assessment were as follows: a follow-up time <6 months (n = 7) [24-30], antiseptics applied to periodontal pockets prior to periodontal treatment (n = 1) , antiseptics applied continuously to worsening sites after an initial periodontal treatment (n = 3) [32-34], repeated periodontal treatment and antiseptics applied at all follow-up visits (n = 1) , and periodontal treatment established only by ultrasonic instruments (n = 3) [36-38].
To summarize the risk of bias for each study, 3 studies were classified as having a low risk of bias (all domains included) [13, 15, 39], 5 studies had a moderate risk (bias for 1 key domain [14, 40-43], and 4 studies were judged to have a high risk of bias (more than 1 domain) [44-47].
The included studies are described in Table 1. Six studies used a split-mouth design [40-42, 44-46], whereas the remaining investigations had a parallel arms design [13-15, 39, 43, 47]. The follow-up period ranged from 6 (10 studies [14, 15, 39-46]) to 12 months (2 studies [13, 47]). Two of the studies had more than one test group (i.e., two  and three  test groups). However, due to the adjunctive use of systemic antibiotics following the SRP, only one test group of one of the aforementioned studies  was included in the current analysis.
The present analysis involved a total of 632 consecutive periodontal patients [13-15, 40-45, 47] and patients enrolled in a regular periodontal maintenance program [39, 46]. In total, 606 (95.8%) patients completed the studies. The mean age of the included patients ranged from 22  to 75 years , and the ratio of included males and females varied from 0.30  to 0.67 . Ten studies [13, 15, 39-44, 46, 47] were based on patient samples from a European population, and 2 studies [14, 45] were based on an Asian population.
Two studies [43, 47] did not report on patient smoking habits, and smokers were excluded in 7 studies [14, 40-42, 44-46]. In 3 investigations [13, 15, 39] that included smoking patients, the proportion of smokers ranged from 16 %  to 55% .
Patient-related data are depicted in Table 1.
Table 1 shows antiseptic materials adjunctively applied during the SRP. Studies were divided into 2 broad groups based on the vehicle employed to deliver the antiseptic agent: adjunctive sustained-release antiseptics (gels, chips, and varnish [14, 15, 39-43, 45, 46]) and adjunctive irrigation with antiseptics (antiseptic delivered by syringe [13, 44, 47]).
Treatment protocols used in the test and control groups are depicted in Table 2. Full-mouth SRP was accomplished in all studies before the application of tested materials. Two studies [14, 39] used placebos in the control groups. In all studies, oral hygiene instructions were given to the patients prior to treatment, and oral hygiene was reinforced at each follow-up visit. Except for 1 study  where patients were prescribed to rinse with 0.12 % chlorhexidine, additional postoperative antiseptic rinsing was restricted in the remaining studies.
Synthesis of results
Meta-analyses were performed only if studies with similar comparisons reported the same outcome measures.
In spite of a high heterogeneity among the included studies (I2=97%, p=0.001), an evaluation of the overall effect of antiseptics used as adjuncts to SRP showed statistically significant changes for the PD (p=0.001; SMD = 1.536, 95% CI = 0.402 to 2.670), CAL (p=0.001; SMD = 1.515, 95% CI=0.289 to 2.741), and BOP (p=0.001; OR = 0.995, 95% CI = 0.0761 to 1.913) values irrespective of the antiseptics delivery vehicle compared to SRP alone.
Forest plots of odds ratios (95% CI) for PD, CAL, and BOP using adjunctive antiseptics with SRP are demonstrated in Figures 2 to 4.
Adjunctive sustained-release antiseptics
Nine studies [14, 15, 39-43, 45, 46] with 405 patients were included in a meta-analysis for PD and CAL changes. The meta-analysis found that a sustained-release delivery of antiseptics resulted in a significantly greater PD reduction compared to SRP alone (p=0.001). There was significant heterogeneity among studies (I2=98%, Q = 454.9179, df = 8, p = 0.001, SMD = 1.977 mm; 95 % CI: 0.470 to 3.485).
Likewise, when considering the CAL changes, a sustained-release delivery system of antiseptics demonstrated statistically significant greater gains in CAL compared to SRP alone (p = 0.001). There was significant heterogeneity among studies (I2=98%, Q = 576.4, df = 8, p=0.001, SMD = 2.174 mm; 95 % CI: 0.438 to 3.909).
Four studies with 124 patients were included in a meta-analysis for the changes of BOP [15, 39, 43, 46]. Its findings pointed to a statistically significant higher reduction in BOP scores when sustained-release antiseptics were applied compared to SRP alone (p = 0.001). Significant heterogeneity among the studies was found (I2=94%, Q = 59.8429, df = 3, p = 0.001, OR = 2.028; 95% CI: 0.119 to 3.936).
Forest plots of odds ratios (95% CI) for PD, BOP reduction, and CAL gains using adjunctive antiseptics for scaling and root planning in a sustained-release vehicle are demonstrated in Figures 5 to 7.
Adjunctive irrigation with antiseptics
For the meta-analysis evaluating the effectiveness of adjunctive subgingival irrigation with antiseptics in terms of PD and CAL changes, 3 studies with 127 patients were included [13, 44, 47]. The results demonstrated that a liquid form of subgingivally applied antiseptics did not significantly change PD values compared to SRP alone (p =0.321). There was significant heterogeneity among studies (I2=89 %, Q = 27.3343 df = 3, p = 0.321, SMD = 0.460 mm; 95% CI: -0.546 to 1.467).
Similarly, liquid forms of antiseptics did not significantly change CAL compared to SRP alone (p =0.7568). There was no significant heterogeneity among studies (I2=0 %, Q = 1.1843, df = 3, p = 0.7568, SMD = 0.0169; 95% CI: -0.292 to 0.326).
Based on the two studies with 107 patients, the additional application of a liquid form of antiseptics did not significantly reduce BOP as compared to SRP alone (p =0.3549) [13, 47]. These studies did not demonstrate significant heterogeneity (I2=7 %, Q = 2.07, df = 2, p = 0.3549, OR = 0.141; 95% CI: -0.217 to 0.499).
Forest plots of odds ratios (95% CI) for PD, BOP reduction, and CAL gains using adjunctive antiseptics for scaling and root planning in additional irrigation studies are demonstrated in Figures 8 to 10.