Adjunct therapy refers to any intracanal procedure going beyond chemomechanical preparation with instruments and traditionally delivered irrigants (excluding interim dressings). It is not clear whether and which of these adjunct therapies have a significant impact on the outcome of root canal treatment [healing of apical periodontitis (AP) and other patient-related outcomes]. This systematic review aimed to analyse available evidence on the effectiveness of adjunct therapy for the treatment of AP in permanent teeth, according to a population, intervention, comparison, outcome, time and study design framework formulated a priori by the European Society of Endodontology. Five electronic databases (PubMed, Embase, Scopus, Cochrane and Web of Science) were searched up to October 2021 to identify clinical studies comparing adjunct therapy to no adjunct therapy in adult patients with AP. Animal studies, reviews, studies with less than 10 patients per arm and studies with a follow-up time of less than 1year, or less than 7 days for postoperative pain, were excluded. The quality of the included studies was appraised by the appropriate tools [Risk of Bias 2 (RoB2) for randomized clinical trials (RCTs) and Newcastle-Ottawa Scale for observational studies]. Meta-analysis was performed using a random-effects model. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Fourteen studies (13 RCTs and one retrospective cohort) fulfilled the inclusion criteria for this review. They evaluated different types of adjunct therapy: antimicrobial photodynamic therapy (aPDT; three studies), diode laser canal irradiation (3), Nd:YAG laser canal irradiation (2), Er;Cr:YSGG laser canal irradiation (1), ozone therapy (2) and ultrasonically activated irrigation (UAI) (4). Radiographical healing was reported in seven studies, but meta-analysis was only possible for UAI (two studies), showing no statistically significant difference in healing after 12 months. Pain after 7 days was reported in seven studies. Meta-analysis on three studies that used aPDT and on two studies using diode laser irradiation showed no significant difference in the prevalence of pain after 7 days between the control and adjunct therapy. According to RoB2 tool, six studies had a high risk of bias, five studies had some concerns, and two studies low risk of bias. The GRADE assessment revealed a very low strength of evidence for diode laser, and low strength of evidence for PDT, ozone and UAI studies. The included studies displayed significant heterogeneity in terms of type of adjunct therapy, technical details per adjunct therapy, outcome reporting and several combinations of these, limiting the potential for meta-analysis. There is insufficient evidence to recommend any adjunctive therapy for the treatment of apical periodontitis. Prospero CRD42021261869.
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