Objectives The aim of the current clinical trial was to evaluate if the oral supplementation of melatonin after nonsurgical periodontal therapy (NSPT) determined a better periodontal healing than NSPT alone, in patients affected by untreated severe periodontitis. Background Melatonin's anti‐inflammatory, antioxidant and immunomodulatory capacities, together with its pharmacokinetic and pharmacodynamic profiles are key characteristics that justify the therapeutic use for the treatment of periodontitis. Methods This is a randomized, triple‐blind, placebo‐controlled study. Twenty patients were blindly randomized either to melatonin or placebo group. The melatonin group received NSPT and melatonin capsules 1 mg per day for 1 month, while the placebo, NSPT, and placebo capsules for 1 month. The patients were evaluated at baseline and 6 months after. Mean change from baseline probing depth (PD) was the primary outcome; site of probing was used as unit of analysis; FMBS (%) and FMPS (%) were also calculated. Mann‐Whitney test was used to evaluate statistical significance (α = 0.05). Results Melatonin was well tolerated by all patients. Both treatments were effective in reducing PD, but no statistical difference was found when comparing posttreatment PD (probing all sites), P = .62. When considering the primary outcome, melatonin administration resulted in greater mean PD change at 6 months if compared to control group: for 4‐5 mm sites 1.86 (0.81) vs 1.04 (0.69), P = .00001 and for sites >5 mm 3.33 (1.43) vs 2.11 (0.96), P = .00012. No difference was found for FMBS and FMPS. Conclusion Current study, within its limitations, concluded that oral administration of melatonin (1 mg per day for 30 days) after one‐stage full mouth NSPT determined a greater change from baseline PD if compared to NSPT alone, in untreated stage III periodontitis. This could provide a non‐pharmacological support to improve periodontal healing of periodontal sites after NSPT.

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Nonsurgical periodontal therapy can be subject to iatrogenesis, which includes all the complications directly or indirectly related to a treatment. These complications include both operator‐dependent harms and errors and the consequences and adverse effects of the therapeutic procedures. The complications arising following nonsurgical periodontal treatment can be categorized as intraoperative and postoperative and can affect both soft and hard tissues at an intra‐oral and extraoral level. Soft‐tissues damage or damage to teeth and restorations can occur while performing the procedure. In the majority of cases, the risk of bleeding associated with nonsurgical therapy is reported to be low and easily controlled by means of local hemostatic measures, even in medicated subjects. Cervicofacial subcutaneous emphysema is not a frequent extraoral intraoperative complication, occurring during the use of air polishing. Moreover, side effects such as pain, fever, and dentine hypersensitivity are frequently reported as a consequence of nonsurgical periodontal therapy and can have a major impact on a patient's perception of the treatment provided. The level of intraoperative pain could be influenced by the types of instruments employed, the characteristics of tips, and the individual level of tolerance of the patient. Unexpected damage to teeth or restorations can also occur as a consequence of procedural errors.