Treatment Outcomes of Venlafaxine and Duloxetine in Refractory Burning Mouth Syndrome Patients

  • Kim, Moon-Jong (Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kho, Hong-Seop (Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University)
  • Received : 2019.07.31
  • Accepted : 2019.08.30
  • Published : 2019.09.30


Purpose: Venlafaxine and duloxetine have been shown to be effective in the treatment of neuropathic pain disorders. However, knowledge about the efficacy of venlafaxine and duloxetine on burning mouth syndrome (BMS) is still insufficient. The purpose of this study was to investigate the efficacy of venlafaxine and duloxetine on refractory BMS patients. Methods: Twelve refractory BMS patients who were prescribed venlafaxine or duloxetine were included in this study. These patients did not respond to previous administration of clonazepam, alpha-lipoic acid, gabapentin, and nortriptyline. All participants were the primary type of BMS patients who had no local and systemic factors related to the oral burning sensation. The intensities of oral symptoms following venlafaxine or duloxetine administration were compared with those before administration and at baseline. Results: Venlafaxine and duloxetine were prescribed to four and nine patients, respectively. One patient was prescribed both medications in turn. Among them, only two patients showed improvement of oral symptoms without side effects. In the other ten patients, symptoms failed to improve. Six of them reported that the drug was ineffective, and four of them stopped taking the medications on their own due to intolerable side effects, such as insomnia, constipation, drowsiness, dizziness, and xerostomia. Conclusions: Venlafaxine and duloxetine may only relieve oral symptoms in a minority of refractory BMS patients. Further large-scale studies are needed to determine the potential clinical factors that could predict the efficacy of venlafaxine and duloxetine.


Supported by : National Research Foundation of Korea (NRF)


  1. Scala A, Checchi L, Montevecchi M, Marini I, Giamberardino MA. Update on burning mouth syndrome: overview and patient management. Crit Rev Oral Biol Med 2003;14:275-291.
  2. Klasser GD, Grushka M, Su N. Burning mouth syndrome. Oral Maxillofac Surg Clin North Am 2016;28:381-396.
  3. Jaaskelainen SK. Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol 2012;123:71-77.
  4. Jaaskelainen SK. Is burning mouth syndrome a neuropathic pain condition? Pain 2018;159:610-613.
  5. Woda A, Navez ML, Picard P, Gremeau C, Pichard-Leandri E. A possible therapeutic solution for stomatodynia (burning mouth syndrome). J Orofac Pain 1998;12:272-278.
  6. Gremeau-Richard C, Woda A, Navez ML, et al. Topical clonazepam in stomatodynia: a randomised placebo-controlled study. Pain 2004;108:51-57.
  7. Amos K, Yeoh SC, Farah CS. Combined topical and systemic clonazepam therapy for the management of burning mouth syndrome: a retrospective pilot study. J Orofac Pain 2011;25:125-130.
  8. Cui Y, Xu H, Chen FM, et al. Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a metaanalysis. Oral Dis 2016;22:503-511.
  9. Liu YF, Kim Y, Yoo T, Han P, Inman JC. Burning mouth syndrome: a systematic review of treatments. Oral Dis 2018;24:325-344.
  10. Lopez-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. Med Oral Patol Oral Cir Bucal 2011;16:e635-e640.
  11. Mott AE, Grushka M, Sessle BJ. Diagnosis and management of taste disorders and burning mouth syndrome. Dent Clin North Am 1993;37:33-71.
  12. Fenelon M, Quinque E, Arrive E, Catros S, Fricain JC. Painrelieving effects of clonazepam and amitriptyline in burning mouth syndrome: a retrospective study. Int J Oral Maxillofac Surg 2017;46:1505-1511.
  13. Sardella A, Lodi G, Demarosi F, Bez C, Cassano S, Carrassi A. Burning mouth syndrome: a retrospective study investigating spontaneous remission and response to treatments. Oral Dis 2006;12:152-155.
  14. Rodriguez-de Rivera-Campillo E, Lopez-Lopez J. Evaluation of the response to treatment and clinical evolution in patients with burning mouth syndrome. Med Oral Patol Oral Cir Bucal 2013;18:e403-e410.
  15. Bellingham GA, Peng PW. Duloxetine: a review of its pharmacology and use in chronic pain management. Reg Anesth Pain Med 2010;35:294-303.
  16. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev 2014;(1):CD007115.
  17. Trouvin AP, Perrot S, Lloret-Linares C. Efficacy of venlafaxine in neuropathic pain: a narrative review of optimized treatment. Clin Ther 2017;39:1104-1122.
  18. Aiyer R, Barkin RL, Bhatia A. Treatment of neuropathic pain with venlafaxine: a systematic review. Pain Med 2017;18:1999-2012.
  19. Mitsikostas DD, Ljubisavljevic S, Deligianni CI. Refractory burning mouth syndrome: clinical and paraclinical evaluation, comorbiities, treatment and outcome. J Headache Pain 2017;18:40.
  20. Mignogna MD, Adamo D, Schiavone V, Ravel MG, Fortuna G. Burning mouth syndrome responsive to duloxetine: a case report. Pain Med 2011;12:466-469.
  21. Kim YD, Lee JH, Shim JH. Duloxetine in the treatment of burning mouth syndrome refractory to conventional treatment: a case report. J Int Med Res 2014;42:879-883.
  22. Ito M, Tokura T, Yoshida K, et al. Five patients with burning mouth syndrome in whom an antidepressant (serotonin-noradrenaline reuptake inhibitor) was not effective, but pregabalin markedly relieved pain. Clin Neuropharmacol 2015;38:158-161.
  23. Kim MJ, Kim J, Kho HS. Comparison between burning mouth syndrome patients with and without psychological problems. Int J Oral Maxillofac Surg 2018;47:879-887.
  24. Kwon M, Altin M, Duenas H, Alev L. The role of descending inhibitory pathways on chronic pain modulation and clinical implications. Pain Pract 2014;14:656-667.
  25. Millan MJ. Descending control of pain. Prog Neurobiol 2002;66:355-474.
  26. Albuquerque RJ, de Leeuw R, Carlson CR, Okeson JP, Miller CS, Andersen AH. Cerebral activation during thermal stimulation of patients who have burning mouth disorder: an fMRI study. Pain 2006;122:223-234.
  27. Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care 2014;8:143-151.
  28. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007;151:737-748.
  29. Argoff C. Mechanisms of pain transmission and pharmacologic management. Curr Med Res Opin 2011;27:2019-2031.
  30. Wong DT, Bymaster FP, Mayle DA, Reid LR, Krushinski JH, Robertson DW. LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology 1993;8:23-33.
  31. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 2001;25:871-880.
  32. Grushka M, Epstein J, Mott A. An open-label, dose escalation pilot study of the effect of clonazepam in burning mouth syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:557-561.
  33. Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. A double-blind study on clonazepam in patients with burning mouth syndrome. Laryngoscope 2012;122:813-816.
  34. Marchand F, Alloui A, Chapuy E, et al. Evidence for a monoamine mediated, opioid-independent, antihyperalgesic effect of venlafaxine, a non-tricyclic antidepressant, in a neurogenic pain model in rats. Pain 2003;103:229-235.
  35. Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM. Efficacy of duloxetine, a potent and balanced serotoninnorepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther 2004;311:576-584.
  36. Lee YC, Chen PP. A review of SSRIs and SNRIs in neuropathic pain. Expert Opin Pharmacother 2010;11:2813-2825.
  37. Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology 2003;60:1284-1289.
  38. Fishbain D, Berman K, Kajdasz DK. Duloxetine for neuropathic pain based on recent clinical trials. Curr Pain Headache Rep 2006;10:199-204.
  39. Razazian N, Baziyar M, Moradian N, Afshari D, Bostani A, Mahmoodi M. Evaluation of the efficacy and safety of pregabalin, venlafaxine, and carbamazepine in patients with painful diabetic peripheral neuropathy. A randomized, double-blind trial. Neurosciences (Riyadh) 2014;19:192-198.
  40. Amr YM, Yousef AA. Evaluation of efficacy of the perioperative administration of Venlafaxine or gabapentin on acute and chronic postmastectomy pain. Clin J Pain 2010;26:381-385.