Management strategies for burning mouth syndrome: a comprehensive review

Burning Mouth Syndrome (BMS) is a complex chronic neuropathic orofacial pain disorder characterized by a persistent burning or dysesthetic sensation in the oral cavity without an identifiable organic cause. The management of BMS has evolved beyond symptom relief to focus on achieving full functional recovery (FFR), which encompasses restoring patients to their usual activities without restrictions, addressing both physical and psychological dimensions. Key pharmacological treatments such as clonazepam and capsaicin are explored in detail, alongside the potential of newer agents like various classes of antidepressants (including tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin and noradrenaline reuptake inhibitors, vortioxetine) and antiepileptics showing promise in addressing the multifactorial nature of BMS. Non-pharmacological interventions, such as cognitive-behavioral therapy (CBT), low-level laser therapy (LLLT), and transcranial magnetic stimulation (TMS), are highlighted for their potential to complement pharmacological treatments. These interventions aim to modify pain perception, reduce psychological burdens, and enhance overall quality of life. Lifestyle modifications, including dietary changes, stress management techniques, improved sleep hygiene, and regular physical activity, are essential components of a holistic treatment plan that addresses modifiable risk factors affecting brain health. The integration of telemedicine and digital health resources is proposed to enhance patient management and accessibility to multidisciplinary care. This review provides a comprehensive update on all available therapeutic approaches for BMS, encompassing pharmacological treatments, non-pharmacotherapeutic interventions, and lifestyle optimization strategies, offering a holistic perspective on managing this condition.

Burning mouth syndrome; Dysesthetic sensation; Full functional recovery; Vortioxetine; Clonazepam

[1] International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia. 2020; 40: 129–221.

[2] Wu S, Zhang W, Yan J, Noma N, Young A, Yan Z. Worldwide prevalence estimates of burning mouth syndrome: a systematic review and meta-analysis. Oral Diseases. 2022; 28: 1431–1440.

[3] Pinto-Pardo N, Rodriguez-Zaninovic MP. Redefining burning mouth syndrome: a nociplastic pain disorder? Journal of Dental Sciences. 2025; 20: 1382–1383.

[4] Parrotte K, Mercado L, Lappen H, Iwashyna TJ, Hough CL, Valley TS, et al. Outcome measures to evaluate functional recovery in survivors of respiratory failure: a scoping review. CHEST Critical Care. 2024; 2: 100084.

[5] Murie-Fernández M, Marzo MM. Predictors of neurological and functional recovery in patients with moderate to severe ischemic stroke: the EPICA study. Stroke Research and Treatment. 2020; 2020: 1419720.

[6] Farag AM, Kuten-Shorrer M, Natto Z, Ariyawardana A, Mejia LM, Albuquerque R, et al. WWOM VII: effectiveness of systemic pharmacotherapeutic interventions in the management of BMS: a systematic review and meta-analysis. Oral Diseases. 2023; 29: 343–368.

[7] Tan HL, Smith JG, Hoffmann J, Renton T. A systematic review of treatment for patients with burning mouth syndrome. Cephalalgia. 2022; 42: 128–161.

[8] Adamo D, Calabria E, Canfora F, Coppola N, Pecoraro G, D’Aniello L, et al. Burning mouth syndrome: analysis of diagnostic delay in 500 patients. Oral Diseases. 2024; 30: 1543–1554.

[9] Gremeau-Richard C, Woda A, Navez ML, Attal N, Bouhassira D, Gagnieu MC, et al. Topical clonazepam in stomatodynia: a randomised placebo-controlled study. Pain. 2004; 108: 51–57.

[10] Adamo D, Pecoraro G, Coppola N, Calabria E, Aria M, Mignogna M. Vortioxetine versus other antidepressants in the treatment of burning mouth syndrome: an open-label randomized trial. Oral Diseases. 2021; 27: 1022–1041.

[11] Suga T, Takenoshita M, Watanabe T, Tu TT, Mikuzuki L, Hong C, et al. Therapeutic dose of amitriptyline for older patients with burning mouth syndrome. Neuropsychiatric Disease and Treatment. 2019; 15: 3599–3607.

[12] Baryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nature Reviews Drug Discovery. 2023; 22: 387–409.

[13] Abrahamsen C, Reme SE, Wangen KR, Lindbæk M, Werner EL. The effects of a structured communication tool in patients with medically unexplained physical symptoms: a cluster randomized trial. eClinicalMedicine. 2023; 65: 102262.

[14] Rossella I, Alessandro V, Naman R, Gary K, Hervé SY. Topical clonazepam for burning mouth syndrome: is it efficacious in patients with anxiety or depression? Journal of Oral Rehabilitation. 2022; 49: 54–61.

[15] Amos K, Yeoh SC, Farah CS. Combined topical and systemic clonazepam therapy for the management of burning mouth syndrome: a retrospective pilot study. Journal of Orofacial Pain. 2011; 25: 125–130.

[16] Roy MS, Sarkar BK, Kundu SK. Site specific binding pattern of benzodiazepines with GABAA receptor and related impact on their activities in the human body: an in silico method based study. Heliyon. 2024; 10: e33929.

[17] Nawafleh S, Qaswal AB, Suleiman A, Alali O, Zayed FM, Al-Adwan MAO, et al. GABA receptors can depolarize the neuronal membrane potential via quantum tunneling of chloride ions: a quantum mathematical study. Cells. 2022; 11: 1145.

[18] Mikami A, Huang H, Hyodo A, Horie K, Yasumatsu K, Ninomiya Y, et al. The role of GABA in modulation of taste signaling within the taste bud. European Journal of Physiology. 2024; 476: 1761–1775.

[19] Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. A double‐blind study on clonazepam in patients with burning mouth syndrome. The Laryngoscope. 2012; 122: 813–816.

[20] Cui Y, Xu H, Chen F, Liu J, Jiang L, Zhou Y, et al. Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a meta‐analysis. Oral Diseases. 2016; 22: 503–511.

[21] Shin HI, Bang JI, Kim GJ, Kim MR, Sun DI, Kim SY. Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions. Scientific Reports. 2023; 13: 7257.

[22] Rodríguez de Rivera Campillo E, López-López J, Chimenos-Küstner E. Response to topical clonazepam in patients with burning mouth syndrome: a clinical study. Bulletin du Groupèment International Pour La Recherche Scientifique en stomatologie & Odontologie. 2010; 49: 19–29.

[23] de Castro LA, Ribeiro-Rotta RF. The effect of clonazepam mouthwash on the symptomatology of burning mouth syndrome: an open pilot study. Pain Medicine. 2014; 15: 2164–2165.

[24] Grushka M, Epstein J, Mott A. An open-label, dose escalation pilot study of the effect of clonazepam in burning mouth syndrome. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 1998; 86: 557–561.

[25] Çınar SL, Kartal D, Pergel T, Borlu M. Effectiveness and safety of clonazepam, pregabalin, and alpha lipoic acid for the treatment of burning mouth syndrome. Journal of Clinical Practice and Research. 2018; 40: 35–38.

[26] Petran EM, Periferakis A, Troumpata L, Periferakis AT, Scheau AE, Badarau IA, et al. Capsaicin: emerging pharmacological and therapeutic insights. Current issues in Molecular Biology. 2024; 46: 7895–7943.

[27] Vyklický L, Nováková-Tousová K, Benedikt J, Samad A, Touska F, Vlachová V. Calcium-dependent desensitization of vanilloid receptor TRPV1: a mechanism possibly involved in analgesia induced by topical application of capsaicin. Physiological Research. 2008; 57: S59–S68.

[28] Vel SK, Ramakrishnan A, Sindya J, Rajanathadurai J, Perumal E. Evaluation of cytotoxic and anti-cancer potential of capsaicin on lung cancer cell line: an in vitro investigation. Cureus. 2024; 16: e68119.

[29] Petruzzi M, Lauritano D, De Benedittis M, Baldoni M, Serpico R. Systemic capsaicin for burning mouth syndrome: short‐term results of a pilot study. Journal of Oral Pathology & Medicine. 2004; 33: 111–114.

[30] Silvestre FJ, Silvestre-Rangil J, Tamarit-Santafé C, Bautista D. Application of a capsaicin rinse in the treatment of burning mouth syndrome. Medicina Oral, Patología Oral y Cirugía Bucal. 2012; 17: e1–e4.

[31] Jørgensen MR, Pedersen AM. Analgesic effect of topical oral capsaicin gel in burning mouth syndrome. Acta Odontologica Scandinavica. 2017; 75: 130–136.

[32] Ricken CM, Péder SNSD, Kamikawa DS, Pieralisi N, Chicarelli M, de Souza Tolentino E. Evaluation of a protocol for topical application of capsaicine gel 0.025 % in the management of burning mouth syndrome correlating its impact on quality of life. International Journal of Odontostomatology. 2021; 15: 443–448.

[33] Marino R, Torretta S, Capaccio P, Pignataro L, Spadari F. Different therapeutic strategies for burning mouth syndrome: preliminary data. Journal of Oral Pathology & Medicine. 2010; 39: 611–616.

[34] Azzi L, Croveri F, Pasina L, Porrini M, Vinci R, Manfredini M, et al. A “burning” therapy for burning mouth syndrome: preliminary results with the administration of topical capsaicin. Journal of Biological Regulators and Homeostatic Agents. 2017; 31: 89–95.

[35] Campisi G, Spadari F, Salvato A. Sucralfate in odontostomatology. Clinical experience. Minerva Stomatologica. 1997; 46: 297–305. (In Italian)

[36] Khan J, Anwer M, Noboru N, Thomas D, Kalladka M. Topical application in burning mouth syndrome. Journal of Dental Sciences. 2019; 14: 352–357.

[37] Goncalves S, Carey B, Farag AM, Kuten-Shorrer M, Natto ZS, Ariyawardana A, et al. WWOM VII: effectiveness of topical interventions in the management of burning mouth syndrome: a systematic review. Oral Diseases. 2023; 29: 3016–3033.

[38] Lebel A, Da Silva Vieira D, Boucher Y. Topical amitriptyline in burning mouth syndrome: a retrospective real-world evidence study. Headache. 2024; 64: 1167–1173.

[39] Hussein F, El-Marssafy LH. Efficacy of different topical amitriptylineconcentrations in the treatment of primary burningmouth syndrome. Romanian Journal of Oral Rehabilitation. 2025; 17: 269–280.

[40] Gramacy A, Villa A. Topical gabapentin solution for the management of burning mouth syndrome: a retrospective study. PLOS ONE. 2023; 18: e0295559.

[41] Tu TTH, Takenoshita M, Matsuoka H, Watanabe T, Suga T, Aota Y, et al. Current management strategies for the pain of elderly patients with burning mouth syndrome: a critical review. BioPsychoSocial Medicine. 2019; 13: 1.

[42] Adamo D, Spagnuolo G. Burning mouth syndrome: an overview and future perspectives. International Journal of Environmental Research and Public Health. 2022; 20: 682.

[43] Bonilla-Jaime H, Sánchez-Salcedo JA, Estevez-Cabrera MM, Molina-Jiménez T, Cortes-Altamirano JL, Alfaro-Rodríguez A. Depression and pain: use of antidepressants. Current Neuropharmacology. 2022; 20: 384–402.

[44] Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. The Journal of Clinical Pharmacology. 2012; 52: 6–17.

[45] Bernatoniene J, Sciupokas A, Kopustinskiene DM, Petrikonis K. Novel drug targets and emerging pharmacotherapies in neuropathic pain. Pharmaceutics. 2023; 15: 1799.

[46] Commons KG, Linnros SE. Delayed antidepressant efficacy and the desensitization hypothesis. ACS Chemical Neuroscience. 2019; 10: 3048–3052.

[47] Yam MF, Loh YC, Tan CS, Khadijah Adam S, Abdul Manan N, Basir R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. International Journal of Molecular Sciences. 2018; 19: 2164.

[48] Staud R. The important role of CNS facilitation and inhibition for chronic pain. International Journal of Clinical Rheumatology. 2013; 8: 639–646.

[49] Pilar-Cuéllar F, Vidal R, Díaz A, Castro E, dos Anjos S, Pascual-Brazo J, et al. Neural plasticity and proliferation in the generation of antidepressant effects: hippocampal implication. Neural Plasticity. 2013; 2013: 537265.

[50] Arumugam V, John V, Augustine N, Jacob T, Joy S, Sen S, et al. The impact of antidepressant treatment on brain-derived neurotrophic factor level: an evidence-based approach through systematic review and meta-analysis. Indian Journal of Pharmacology. 2017; 49: 236–242.

[51] Obata H. Analgesic mechanisms of antidepressants for neuropathic pain. International Journal of Molecular Sciences. 2017; 18: 2483.

[52] Barygin OI, Nagaeva EI, Tikhonov DB, Belinskaya DA, Vanchakova NP, Shestakova NN. Inhibition of the NMDA and AMPA receptor channels by antidepressants and antipsychotics. Brain Research. 2017; 1660: 58–66.

[53] Herrero JF, Laird JMA, Lopez-Garcia JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Progress in Neurobiology. 2000; 61: 169–203.

[54] Leonard B, Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neuroscience & Biobehavioral Reviews. 2012; 36: 764–785.

[55] Kishore J, Shaikh F, Mirza S, Raffat MA, Ikram S, Akram Z. Cytokine levels and their role in the etiopathogenesis of burning mouth syndrome: a systematic review. Cephalalgia. 2019; 39: 1586–1594.

[56] Gonçalves DR, Botelho LM, Carrard VC, Martins MAT, Visioli F. Amitriptyline effectiveness in burning mouth syndrome: an in-depth case series analysis. Gerodontology. 2024; 41: 547–554.

[57] Nagamine T. Responsiveness to amitriptyline in burning mouth syndrome. Gerodontology. 2025; 42: 143–144.

[58] Nagamine T, Watanabe T, Toyofuku A. QTc shortening on electrocardiogram with amitriptyline may indicate no effect on pain relief in burning mouth syndrome. Clinical Neuropharmacology. 2024; 47: 33–36.

[59] Kim JY, Kim YS, Ko I, Kim DK. Association between burning mouth syndrome and the development of depression, anxiety, dementia, and parkinson disease. JAMA Otolaryngology—Head & Neck Surgery. 2020; 146: 561–569.

[60] Brueckle M, Thomas ET, Seide SE, Pilz M, Gonzalez-Gonzalez AI, Nguyen TS, et al. Adverse drug reactions associated with amitriptyline—protocol for a systematic multiple-indication review and meta-analysis. Systematic Reviews. 2020; 9: 59.

[61] Anderson IM. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Depression and Anxiety. 1998; 7: 11–17.

[62] Srifuengfung M, Pennington BRT, Lenze EJ. Optimizing treatment for older adults with depression. Therapeutic Advances in Psychopharmacology. 2023; 13: 20451253231212327.

[63] Mortensen JK, Andersen G. Safety considerations for prescribing SSRI antidepressants to patients at increased cardiovascular risk. Expert Opinion on Drug Safety. 2022; 21: 467–475.

[64] Maina G, Vitalucci A, Gandolfo S, Bogetto F. Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study. The Journal of Clinical Psychiatry. 2002; 63: 38–43.

[65] Yamazaki Y, Hata H, Kitamori S, Onodera M, Kitagawa Y. An open-label, noncomparative, dose escalation pilot study of the effect of paroxetine in treatment of burning mouth syndrome. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology. 2009; 107: e6–e11.

[66] Ohga N, Yamazaki Y, Sato J, Hata H, Murata T, Sakata K, et al. Dose escalation effectiveness and tolerability of paroxetine in patients with burning mouth syndrome and depressive conditions. Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 2015; 27: 402–406.

[67] Barakat A, Hamdy MM, Elbadr MM. Uses of fluoxetine in nociceptive pain management: a literature overview. European Journal of Pharmacology. 2018; 829: 12–25.

[68] Catalisano G, Campione GM, Spurio G, Galvano AN, di Villalba CP, Giarratano A, et al. Neuropathic pain, antidepressant drugs, and inflammation: a narrative review. Journal of Anesthesia, Analgesia and Critical Care. 2024; 4: 67.

[69] de Gandarias JM, Echevarrı́a E, Acebes I, Abecia LC, Casis O, Casis L. Effects of fluoxetine administration on mu-opoid receptor immunostaining in the rat forebrain. Brain Research. 1999; 817: 236–240.

[70] Zoric B, Jankovic L, Kuzmanovic Pficer J, Zidverc-Trajkovic J, Mijajlovic M, Stanimirovic D. The efficacy of fluoxetine in BMS—a cross-over study. Gerodontology. 2018; 35: 123–128.

[71] Robinson C, Dalal S, Chitneni A, Patil A, Berger AA, Mahmood S, et al. A look at commonly utilized serotonin noradrenaline reuptake inhibitors (SNRIs) in chronic pain. Health Psychology Research. 2022; 10: 32309.

[72] Ziółkowska N, Lewczuk B. Norepinephrine is a major regulator of pineal gland secretory activity in the domestic goose (Anser anser). Frontiers in Physiology. 2021; 12: 664117.

[73] Mignogna MD, Adamo D, Schiavone V, Ravel MG, Fortuna G. Burning mouth syndrome responsive to duloxetine: a case report. Pain Medicine. 2011; 12: 466–469.

[74] Nagashima W, Kimura H, Ito M, Tokura T, Arao M, Aleksic B, et al. Effectiveness of duloxetine for the treatment of chronic nonorganic orofacial pain. Clinical Neuropharmacology. 2012; 35: 273–277.

[75] Kim YD, Lee JH, Shim JH. Duloxetine in the treatment of burning mouth syndrome refractory to conventional treatment: a case report. The Journal of International Medical Research. 2014; 42: 879–883.

[76] Kim MJ, Kim PJ, Kim HG, Kho HS. Prediction of treatment outcome in burning mouth syndrome patients using machine learning based on clinical data. Scientific Reports. 2021; 11: 15396.

[77] Fagiolini A, Comandini A, Dell’Osso MC, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012; 26: 1033–1049.

[78] Fagiolini A, González-Pinto A, Miskowiak KW, Morgado P, Young AH, Vieta E. Role of trazodone in treatment of major depressive disorder: an update. Annals of General Psychiatry. 2023; 22: 32.

[79] Tammiala-Salonen T, Forssell H. Trazodone in burning mouth pain: a placebo-controlled, double-blind study. Journal of Orofacial Pain. 1999; 13: 83–88.

[80] Choi HG, Jung EJ, Lee WY, Kim H, Cha W, Hah JH. Comparison of pharmacological treatments for burning mouth syndrome. Korean Journal of Otolaryngology—Head and Neck Surgery. 2012; 55: 707–711.

[81] Zheng Y, Lv T, Wu J, Lyu Y. Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis. Scientific Reports. 2022; 12: 14453.

[82] Gonda X, Sharma SR, Tarazi FI. Vortioxetine: a novel antidepressant for the treatment of major depressive disorder. Expert Opinion on Drug Discovery. 2019; 14: 81–89.

[83] Adell A. Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety. IDrugs. 2010; 13: 900–910.

[84] D’Agostino A, English CD, Rey JA. Vortioxetine (brintellix): a new serotonergic antidepressant. Pharmacy and Therapeutics. 2015; 40: 36–40.

[85] Mørk A, Pehrson A, Brennum LT, Nielsen SM, Zhong H, Lassen AB, et al. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. The Journal of Pharmacology and Experimental Therapeutics. 2012; 340: 666–675.

[86] Westrich L, Haddjeri N, Dkhissi-Benyahya O, Sánchez C. Involvement of 5-HT₇ receptors in vortioxetine’s modulation of circadian rhythms and episodic memory in rodents. Neuropharmacology. 2015; 89: 382–390.

[87] Adamo D, Pecoraro G, Aria M, Favia G, Mignogna MD. Vortioxetine in the treatment of mood disorders associated with burning mouth syndrome: results of an open-label, flexible-dose pilot study. Pain Medicine. 2020; 21: 185–194.

[88] Zhang Y, Lai S, Zhang J, Wang Y, Zhao H, He J, et al. The effectiveness of vortioxetine on neurobiochemical metabolites and cognitive of major depressive disorders patients: a 8-week follow-up study. Journal of Affective Disorders. 2024; 351: 799–807.

[89] Fink KB, Göthert M. 5-HT receptor regulation of neurotransmitter release. Pharmacological Reviews. 2007; 59: 360–417.

[90] Talmon M, Rossi S, Pastore A, Cattaneo CI, Brunelleschi S, Fresu LG. Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human monocytes/macrophages. British Journal of Pharmacology. 2018; 175: 113–124.

[91] Waller JA, Chen F, Sánchez C. Vortioxetine promotes maturation of dendritic spines in vitro: a comparative study in hippocampal cultures. Neuropharmacology. 2016; 103: 143–154.

[92] Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. International Clinical Psychopharmacology. 2012; 27: 215–223.

[93] Adamo D, Calabria E, Coppola N, Pecoraro G, Mignogna MD. Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update. Therapeutic Advances in Psychopharmacology. 2021; 11: 20451253211034320.

[94] Zuena AR, Maftei D, Alemà GS, Dal Moro F, Lattanzi R, Casolini P, et al. Multimodal antidepressant vortioxetine causes analgesia in a mouse model of chronic neuropathic pain. Molecular Pain. 2018; 14: 1744806918808987.

[95] Wallace A, Pehrson AL, Sánchez C, Morilak DA. Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats. The International Journal of Neuropsychopharmacology. 2014; 17: 1695–1706.

[96] Ortega JE, Mendiguren A, Pineda J, Meana JJ. Regulation of central noradrenergic activity by 5-HT3 receptors located in the locus coeruleus of the rat. Neuropharmacology. 2012; 62: 2472–2479.

[97] Brenchat A, Nadal X, Romero L, Ovalle S, Muro A, Sánchez-Arroyos R, et al. Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity. Pain. 2010; 149: 483–484.

[98] Riga MS, Sánchez C, Celada P, Artigas F. Involvement of 5-HT 3 receptors in the action of vortioxetine in rat brain: focus on glutamatergic and GABAergic neurotransmission. Neuropharmacology. 2016; 108: 73–81.

[99] Baldwin DS, Chrones L, Florea I, Nielsen R, Nomikos GG, Palo W, et al. The safety and tolerability of vortioxetine: analysis of data from randomized placebo-controlled trials and open-label extension studies. Journal of Psychopharmacology. 2016; 30: 242–252.

[100] Inoue T, Fujimoto S, Marumoto T, Kitagawa T, Ishida K, Nakajima T, et al. Early improvement with vortioxetine predicts response and remission: a post hoc analysis of data from a clinical trial conducted in Japan. Neuropsychiatric Disease and Treatment. 2021; 17: 3735–3741.

[101] Adamo D, Canfora F, Pecoraro G, Leuci S, Coppola N, Marenzi G, et al. Vortioxetine versus SSRI/SNRI with pregabalin augmentation in treatment-resistant burning mouth syndrome: a prospective clinical trial. Current Neuropharmacology. 2025; 23: 800–819.

[102] Davari M, Amani B, Amani B, Khanijahani A, Akbarzadeh A, Shabestan R. Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis. The Korean Journal of Pain. 2020; 33: 3–12.

[103] Alles SRA, Cain SM, Snutch TP. Pregabalin as a pain therapeutic: beyond calcium channels. Frontiers in Cellular Neuroscience. 2020; 14: 83.

[104] Takeuchi Y, Takasu K, Ono H, Tanabe M. Pregabalin, S-(+)-3-isobutylgaba, activates the descending noradrenergic system to alleviate neuropathic pain in the mouse partial sciatic nerve ligation model. Neuropharmacology. 2007; 53: 842–853.

[105] Tassone DM, Boyce E, Guyer J, Nuzum D. Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clinical Therapeutics. 2007; 29: 26–48.

[106] Ito M, Tokura T, Yoshida K, Nagashima W, Kimura H, Umemura E, et al. Five patients with burning mouth syndrome in whom an antidepressant (serotonin-noradrenaline reuptake inhibitor) was not effective, but pregabalin markedly relieved pain. Clinical Neuropharmacology. 2015; 38: 158–161.

[107] Heo J, Jeon JW, Ok SM, Jeong SH, Ahn YW. Effects of pregabalin in primary burning mouth syndrome patients unresponsive to topical clonazepam treatment: a retrospective pilot study. Journal of Oral Medicine and Pain. 2016; 41: 1–6.

[108] López-D’alessandro E, Escovich L. Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial. Medicina Oral, Patología Oral y Cirugía Bucal. 2011; 16: e635–e640.

[109] Heckmann SM, Heckmann JG, Ungethüm A, Hujoel P, Hummel T. Gabapentin has little or no effect in the treatment of burning mouth syndrome—results of an open-label pilot study. European Journal of Neurology. 2006; 13: e6–e7.

[110] White TL, Kent PF, Kurtz DB, Emko P. Effectiveness of gabapentin for treatment of burning mouth syndrome. Archives of Otolaryngology—Head & Neck Surgery. 2004; 130: 786–788.

[111] Adamo D. Burning mouth syndrome: unlocking the future of pharmacological treatment. Journal of Oral Pathology & Medicine. 2025; 54: 251–262.

[112] Seidel S, Aigner M, Wildner B, Sycha T, Pablik E. Antipsychotics for the treatment of neuropathic pain in adults. Cochrane Database of Systematic Reviews. 2018; 2018: CD012916.

[113] Ueda N, Kodama Y, Hori H, Umene W, Sugita A, Nakano H, et al. Two cases of burning mouth syndrome treated with olanzapine. Psychiatry and Clinical Neurosciences. 2008; 62: 359–361.

[114] Umezaki Y, Takenoshita M, Toyofuku A. Low-dose aripiprazole for refractory burning mouth syndrome. Neuropsychiatric Disease and Treatment. 2016; 12: 1229–1231.

[115] Takenoshita M, Motomura H, Toyofuku A. Low-dose aripiprazole augmentation in amitriptyline-resistant burning mouth syndrome: results from two cases. Pain Medicine. 2017; 18: 814–815.

[116] Poyurovsky M, Weizman A. Quetiapine in the treatment of comorbid burning mouth syndrome and bipolar II depression. Journal of Clinical Psychopharmacology. 2024; 44: 432–433.

[117] Demarosi F, Tarozzi M, Lodi G, Canegallo L, Rimondini L, Sardella A. The effect of levosulpiride in burning mouth syndrome. Minerva Stomatologica. 2007; 56: 21–26.

[118] Yang Z, Li C, Wang Y, Yang J, Yin Y, Liu M, et al. Melatonin attenuates chronic pain related myocardial ischemic susceptibility through inhibiting RIP3-MLKL/CaMKII dependent necroptosis. Journal of Molecular and Cellular Cardiology. 2018; 125: 185–194.

[119] Kaur T, Shyu B. Melatonin: a new-generation therapy for reducing chronic pain and improving sleep disorder-related pain. Advances in Experimental Medicine and Biology. 2018; 2: 229–251.

[120] Danilov A, Kurganova J. Melatonin in chronic pain syndromes. Pain and Therapy. 2016; 5: 1–17.

[121] Varoni E, Lo Faro A, Lodi G, Carrassi A, Iriti M, Sardella A. Melatonin treatment in patients with burning mouth syndrome: a triple-blind, placebo-controlled, crossover randomized clinical trial. Journal of Oral & Facial Pain and Headache. 2018; 32: 178–188.

[122] Nosratzehi T, Payandeh A, Arbab K. Evaluation of the effect of melatonin in patients with Burning mouth syndrome: a double-blind, placebo-controlled randomized clinical trial. Brazilian Journal of Pharmaceutical Sciences. 2023; 59: e21748.

[123] Castillo-Felipe C, Tvarijonaviciute A, López-Arjona M, Pardo-Marin L, Pons-Fuster E, López-Jornet P. Response to treatment with melatonin and clonazepam versus placebo in patients with burning mouth syndrome. Journal of Clinical Medicine. 2022; 11: 2516.

[124] Oh SN, Myung SK, Jho HJ. Analgesic efficacy of melatonin: a meta-analysis of randomized, double-blind, placebo-controlled trials. Journal of Clinical Medicine. 2020; 9: 1553.

[125] Cassanego G, Rodrigues P, De Freitas Bauermann L, Trevisan G. Evaluation of the analgesic effect of ɑ-lipoic acid in treating pain disorders: a systematic review and meta-analysis of randomized controlled trials. Pharmacological Research. 2022; 177: 106075.

[126] Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, et al. Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules. 2019; 9: 356.

[127] Orellana-Donoso M, López-Chaparro M, Barahona-Vásquez M, Santana-Machuca A, Bruna-Mejias A, Nova-Baeza P, et al. Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: a systematic review and meta-analysis. Medicine. 2023; 102: e35368.

[128] Viana MDM, Lauria PSS, Lima AA, Opretzka LCF, Marcelino HR, Villarreal CF. Alpha-lipoic acid as an antioxidant strategy for managing neuropathic pain. Antioxidants. 2022; 11: 2420.

[129] Palacios-Sánchez B, Moreno-López LA, Cerero-Lapiedra R, Llamas-Martínez S, Esparza-Gómez G. Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial. Medicina Oral, Patología Oral y Cirugía Bucal. 2015; 20: e435–e440.

[130] Femiano F, Gombos F, Scully C. Burning mouth syndrome: open trial of psychotherapy alone, medication with alpha-lipoic acid (thioctic acid), and combination therapy. Medicina Oral. 2004; 9: 8–13.

[131] Cavalcanti DR, Da Silveira FRX. Alpha lipoic acid in burning mouth syndrome—a randomized double‐blind placebo‐controlled trial. Journal of Oral Pathology & Medicine. 2009; 38: 254–261.

[132] Clayton P, Hill M, Bogoda N, Subah S, Venkatesh R. Palmitoylethanolamide: a natural compound for health management. International Journal of Molecular Sciences. 2021; 22: 5305.

[133] Paterniti I, Impellizzeri D, Crupi R, Morabito R, Campolo M, Esposito E, et al. Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma. Journal of Neuroinflammation. 2013; 10: 20.

[134] Petrosino S, Di Marzo V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. British Journal of Pharmacology. 2017; 174: 1349–1365.

[135] Petrosino S, Schiano Moriello A, Cerrato S, Fusco M, Puigdemont A, De Petrocellis L, et al. The anti‐inflammatory mediator palmitoylethanolamide enhances the levels of 2‐arachidonoyl‐glycerol and potentiates its actions at TRPV1 cation channels. British Journal of Pharmacology. 2016; 173: 1154–1162.

[136] Ho WS, Barrett DA, Randall MD. ‘Entourage’ effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors. British Journal of Pharmacology. 2008; 155: 837–846.

[137] Ottaviani G, Rupel K, Gobbo M, Poropat A, Zoi V, Faraon M, et al. Efficacy of ultramicronized palmitoylethanolamide in burning mouth syndrome-affected patients: a preliminary randomized double-blind controlled trial. Clinical Oral Investigations. 2019; 23: 2743–2750.

[138] Chirchiglia D, Chirchiglia P, Marotta R, Gallelli L. Add-on administration of ultramicronized palmitoylethanolamide in the treatment of new-onset burning mouth syndrome. International Medical Case Reports Journal. 2019; 12: 39–42.

[139] Lim JA, Choi SH, Lee WJ, Jang JH, Moon JY, Kim YC, et al. Cognitive-behavioral therapy for patients with chronic pain: implications of gender differences in empathy. Medicine. 2018; 97: e10867.

[140] Nakao M, Shirotsuki K, Sugaya N. Cognitive-behavioral therapy for management of mental health and stress-related disorders: recent advances in techniques and technologies. BioPsychoSocial Medicine. 2021; 15: 16.

[141] Curtiss JE, Levine DS, Ander I, Baker AW. Cognitive-behavioral treatments for anxiety and stress-related disorders. Focus. 2021; 19: 184–189.

[142] Toussaint L, Nguyen QA, Roettger C, Dixon K, Offenbächer M, Kohls N, et al. Effectiveness of progressive muscle relaxation, deep breathing, and guided imagery in promoting psychological and physiological states of relaxation. Evidence-Based Complementary and Alternative Medicine. 2021; 2021: 5924040.

[143] Frank DL, Khorshid L, Kiffer JF, Moravec CS, McKee MG. Biofeedback in medicine: who, when, why and how? Mental Health in Family Medicine. 2010; 7: 85–91.

[144] Hofmann SG, Asnaani A, Vonk IJJ, Sawyer AT, Fang A. The efficacy of cognitive behavioral therapy: a review of meta-analyses. Cognitive Therapy and Research. 2012; 36: 427–440.

[145] Komiyama O, Nishimura H, Makiyama Y, Iida T, Obara R, Shinoda M, et al. Group cognitive-behavioral intervention for patients with burning mouth syndrome. Journal of Oral Science. 2013; 55: 17–22.

[146] Bergdahl J, Anneroth G, Ferris H. Cognitive therapy in the treatment of patients with resistant burning mouth syndrome: a controlled study. Journal of Oral Pathology & Medicine. 1995; 24: 213–215.

[147] Richardson T, Enrique A, Earley C, Adegoke A, Hiscock D, Richards D. The acceptability and initial effectiveness of “space from money worries”: an online cognitive behavioral therapy intervention to tackle the link between financial difficulties and poor mental health. Frontiers in Public Health. 2022; 10: 739381.

[148] Zhang Z, Zhang L, Zhang G, Jin J, Zheng Z. The effect of CBT and its modifications for relapse prevention in major depressive disorder: a systematic review and meta-analysis. BMC Psychiatry. 2018; 18: 50.

[149] Humphris GM, Longman LP, Field EA. Cognitive-behavioural therapy for idiopathic burning mouth syndrome: a report of two cases. British Dental Journal. 1996; 181: 204–208.

[150] Brailo V, Firić M, Vučićević Boras V, Andabak Rogulj A, Krstevski I, Alajbeg I. Impact of reassurance on pain perception in patients with primary burning mouth syndrome. Oral Diseases. 2016; 22: 512–516.

[151] Mahmood D, Ahmad A, Sharif F, Arslan SA. Clinical application of low-level laser therapy (photo-biomodulation therapy) in the management of breast cancer-related lymphedema: a systematic review. BMC Cancer. 2022; 22: 937.

[152] Pezelj-Ribarić S, Kqiku L, Brumini G, Urek MM, Antonić R, Kuiš D, et al. Proinflammatory cytokine levels in saliva in patients with burning mouth syndrome before and after treatment with low-level laser therapy. Lasers in Medical Science. 2013; 28: 297–301.

[153] Barbosa RI, Fonseca Mde C, Rodrigues EK, Tamanini G, Marcolino AM, Mazzer N, et al. Efficacy of low-level laser therapy associated to orthoses for patients with carpal tunnel syndrome: a randomized single-blinded controlled trial. Journal of Back and Musculoskeletal Rehabilitation. 2016; 29: 459–466.

[154] Shaikh-Kader A, Houreld NN, Rajendran NK, Abrahamse H. Levels of cyclooxygenase 2, interleukin-6, and tumour necrosis factor-α in fibroblast cell culture models after photobiomodulation at 660 nm. Oxidative Medicine and Cellular Longevity. 2021; 2021: 6667812.

[155] Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophysics. 2017; 4: 337–361.

[156] Lu C, Yang C, Li X, Du G, Zhou X, Luo W, et al. Effects of low-level laser therapy on burning pain and quality of life in patients with burning mouth syndrome: a systematic review and meta-analysis. BMC Oral Health. 2023; 23: 734.

[157] Spanemberg JC, Segura-Egea JJ, Rodríguez-de Rivera-Campillo E, Jané-Salas E, Salum FG, López-López J. Low-level laser therapy in patients with burning mouth syndrome: a double-blind, randomized, controlled clinical trial. Journal of Clinical and Experimental Dentistry. 2019; 11: e162–e169.

[158] Umezaki Y, Badran BW, DeVries WH, Moss J, Gonzales T, George MS. The efficacy of daily prefrontal repetitive transcranial magnetic stimulation (rTMS) for burning mouth syndrome (BMS): a randomized controlled single-blind study. Brain Stimulation. 2016; 9: 234–242.

[159] Umezaki Y, Badran BW, Gonzales TS, George MS. Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome. International Journal of Oral and Maxillofacial Surgery. 2015; 44: 1048–1051.

[160] Sánchez-Cuesta FJ, González-Zamorano Y, Arroyo-Ferrer A, Avellanal M, Fernández-Carnero J, Romero JP. Transcranial direct current stimulation (tDCS) combined with therapeutic exercise and cognitive rehabilitation to treat a case of burning mouth syndrome (BMS) related pain. Applied Sciences. 2021; 11: 11538.

[161] Siebner HR, Funke K, Aberra AS, Antal A, Bestmann S, Chen R, et al. Transcranial magnetic stimulation of the brain: what is stimulated?—A consensus and critical position paper. Clinical Neurophysiology. 2022; 140: 59–97.

[162] Moffa AH, Brunoni AR, Nikolin S, Loo CK. Transcranial direct current stimulation in psychiatric disorders: a comprehensive review. Psychiatric Clinics of North America. 2018; 41: 447–463.

[163] Thair H, Holloway AL, Newport R, Smith AD. Transcranial direct current stimulation (tDCS): a Beginner’s guide for design and implementation. Frontiers in Neuroscience. 2017; 11: 641.

[164] Canfora F, Calabria E, Cuocolo R, Ugga L, Buono G, Marenzi G, et al. Burning fog: cognitive impairment in burning mouth syndrome. Frontiers in Aging Neuroscience. 2021; 13: 727417.

[165] Huston P. A sedentary and unhealthy lifestyle fuels chronic disease progression by changing interstitial cell behaviour: a network analysis. Frontiers in Physiology. 2022; 13: 904107.

[166] Wang M, Wang Y, Zhang Y, Zhang W, Wang Y, Fan R, et al. High intake of dietary cholesterol decreases the risk of all-cause dementia and ad dementia: a results from framingham offspring cohort. The Journal of Prevention of Alzheimer’s Disease. 2023; 10: 748–755.

[167] Adamo D, Canfora F, Calabria E, Coppola N, Sansone M, Spagnuolo G, et al. burning mouth syndrome and hypertension: prevalence, gender differences and association with pain and psycho-social characteristics—a case control study. International Journal of Environmental Research and Public Health. 2023; 20: 2040.

[168] Lumley S, Yu D, Wilkie R, Jordan KP, Peat G. Chronic pain–mental health comorbidity and excess prevalence of health risk behaviours: a cross-sectional study. Primary Health Care Research & Development. 2024; 25: e15.

[169] Encinosa W, Bernard D, Valdez RB. The association between smoking, chronic pain, and prescription opioid use: 2013–2021. The Journal of Pain. 2025; 26: 104707.

[170] Canfora F, Cataldi M, Mignogna MD, Ottaviani G, Leuci S, Coppola N, et al. Blueprint persona and information and communication technology interventions: addressing unmet needs in burning mouth syndrome care. The Journal of Evidence-Based Dental Practice. 2025; 25: 102047.

[171] Hopkinson LD, Jafari S, Frempong E, Zarghom S. Onset of chronic pain triggered by a lifestyle-change-based weight loss and exercise regimen. BMJ Case Reports. 2025; 18: e263172.

[172] Jogna F, Graenicher A A, Rey-Millet Q, Groz A, De Grasset J, Stollar F, et al. Pharmacological and non-pharmacological approaches to temporomandibular disorder chronic pain: a narrative review. Pain Management. 2025; 15: 285–296.