BackgroundBurning mouth syndrome (BMS) is an intraoral burning or dysaesthetic sensation, recurring daily for more than two hours during the period longer than 3 months. The objective was to evaluate and analyse the efficacy of serotonin reuptake inhibitor fluoxetine on psychological factors, as well as on pain in participants with BMS.MethodsIn a 6‐month study, 100 participants with primary and secondary BMS were divided into two groups—fluoxetine and control (placebo) and examined by the dentist and the neurologist. Depression and anxiety were estimated by Hamilton Scale for Depression (HAM‐D) and Anxiety (HAM‐A) and Beck Depression Inventory (BDI) and the pain intensity by visual analogue scale (VAS).ResultsMean age of the participants was 60.33 in fluoxetine group and 67.4 in control group. Most of the participants were female—74% in the fluoxetine and 78% in the control group. Statistical difference between the fluoxetine and the control group was found in HAM‐D results (P < .05). Values of other scales and VAS decreased significantly after the therapy in both groups (P < .05).ConclusionsOur trial results indicate that fluoxetine therapy not only improves the psychological status of participants with BMS but also fluoxetine decreases the intensity of pain in these patients.