Melatonin treatment in patients with burning mouth syndrome: A triple-blind, placebo-controlled, crossover randomized clinical trial

Aims: To evaluate the efficacy of melatonin compared to placebo in reducing pain associated with burning mouth syndrome (BMS), as well as side effects of treatment and effects on sleep quality, anxiety, and serum and salivary melatonin levels. Methods: In this triple-blind, randomized clinical trial, 20 BMS patients (mean age ± standard deviation: 64.4 ± 11.5 years; range: 35 to 82 years) were enrolled to receive melatonin (12 mg/day) or placebo for 8 weeks in a crossover design. After treatment, changes in pain from baseline were ascertained by patient self-assessment with a verbal category scale and a visual analog scale. Secondary outcomes included evaluation of changes in sleep quality and anxiety. Data were subjected to analysis of variance (ANOVA), Fisher exact test, paired t test, Wilcoxon signed rank test, or chi-square test, as appropriate. Results: Melatonin was not superior to placebo in reducing pain. Melatonin significantly improved anxiety scores, though without strong clinical relevance. Independent of treatment, sleep quality did not significantly change during the trial, although melatonin slightly increased the number of hours slept. After active treatment, the mean ± standard error serum melatonin level peaked at 1,520 ± 646 pg/mL. A generally safe pharmacologic profile of melatonin was observed, and the placebo and melatonin treatments resulted in similar adverse effects. Conclusion: Within the limitations of this study, melatonin did not exhibit higher efficacy than placebo in relieving pain in BMS patients.