Objective: to evaluate the efficacy of melatonin and clonazepam versus placebo in patients with burning mouth syndrome (BMS). Methods: a prospective double-blind study was carried out in patients with BMS and randomized to three groups: melatonin (1 mg once a day), clonazepam (0.5 mg/twice a day), or a placebo once a day, for 8 weeks. The clinical changes were evaluated, including xerostomia, the Oral Health Impact Profile 14 (OHIP-14) score, Pittsburg Sleep Quality Index, and the Hospital Anxiety and Depression Scale (HADS). Oxygen saturation and heart rate were recorded, with an analysis of salivary biomarkers in the forms of oxytocin, ferritin, adenosine deaminase (ADA), total proteins, and alpha-amylase. Results: a total of 64 patients were analyzed. A significant decrease in burning sensation was recorded with melatonin (7.8 ± 1.54 pre-treatment, 5.78 ± 2.54 post-treatment; p < 0.001) and clonazepam (8.75 ± 1.2 pre-treatment, 5.5 ± 3.6 post-treatment (p < 0.01). With regard to quality of life (OHIP-14), significant improvements were observed before and after the administration of melatonin (p < 0.001) and clonazepam (p = 0.001). On the other hand, with regard to the changes in salivary biomarkers following treatment, negative correlations were found between oxytocin and drainage (r = −0.410; p = 0.009) and between the HADS-D score and ferritin (r = −0.312; p = 0.05). While salivary amylase showed positive correlation with heart rate (r = 0.346; p = 0.029) and oxygen saturation (r = 0.419; p = 0.007). Conclusions: melatonin and clonazepam were shown to be effective at reducing the burning sensation and improving quality of life. Both drugs were found to be safe, with no major adverse effects in patients with BMS. Melatonin may be regarded as an alternative treatment for patients with BMS, though further studies are needed to confirm its effectiveness.
Keywords: burning mouth syndrome; clonazepam; melatonin; pain; placebo; sleep; xerostomia.