Clinical Features Affecting the Efficacy of Systemic Clonazepam for Management of Burning Mouth Syndrome

구강작열감증후군의 치료를 위한 전신적 클로나제팜의 투여 시 환자의 임상적 특징에 따른 효능의 차이에 관한 연구

  • Min, Bo-Kyong (Department of Oral Medicine, School of Dentistry, Kyungpook National University) ;
  • Jung, Jae-Kwang (Department of Oral Medicine, School of Dentistry, Kyungpook National University) ;
  • Choi, Jae-Kap (Department of Oral Medicine, School of Dentistry, Kyungpook National University)
  • 민보경 (경북대학교 치의학전문대학원 구강내과학 교실) ;
  • 정재광 (경북대학교 치의학전문대학원 구강내과학 교실) ;
  • 최재갑 (경북대학교 치의학전문대학원 구강내과학 교실)
  • Received : 2012.07.25
  • Accepted : 2012.08.12
  • Published : 2012.09.30


Burning mouth syndrome(BMS) is defined as chronic, painful burning sensation in the oral mucosa. Treatments for BMS include medication and psychiatric interventions. Capsaicin, alpha-lipoic acid, and topical and systemic clonazepam showed more effective in reducing the symptoms of BMS in the previous studies. The purpose of this study is to evaluate of the therapeutic efficacy of systemic clonazepam in BMS and to elucidate the relationships between such a efficacy and various clinical features, including age, pain intensity, pain duration, previous dental history and condition of oral mucosa. A retrospective clinical records audit was performed of patients diagnosed with BMS between January 2011 and August 2012. Patients were prescribed 0.5 mg clonazepam two times daily. Pain was assessed by patients on an 11-point numeric rating scale (NRS; 0 to 10) before and 1-2 weeks after systemic administration of clonazepam. The efficacy of clonazepam was evaluated in terms of patient's age, initial pain intensity, pain duration, presence or absence of precipitating event, condition of the tongue, presence or absence of denture. A total of 50 patients (46 women, 4 men) were included in this study. The patients were divided into two or three groups according to above clinical features. The amount of mean NRS reduction in patients with severe initial pain was $3.33{\pm}2.74$, whereas that in patients with mild initial pain was $1.64{\pm}1.54$. The amount of mean NRS reduction in oldest patients was $3.53{\pm}1.94$ (${\geq}$70yrs), and those in another younger patients were $2.88{\pm}1.80$(< 60yrs) and $1.54{\pm}2.86$(60yrs ${\leq}$ age < 70yrs), respectively. It was concluded that the older patients and the patients with higher intensity of initial pain tend to show better efficacy of clonazepam. However, There were no statistically significant differences according to pain duration, presence or absence of precipitating events, tongue fissuring, and wearing dentures.


Supported by : Kyungpook National University


  1. Ship JA, Grushka M, Lipton JA, Mott AE, Sessle BJ, Dionne RA. Burning mouth syndrome: and update. J Am Dent Assoc 1995;126:842-53.
  2. Grushka M, Epstein JB, Gorsky M. Burning mouth syndrome. Am Fam Physician. 2002 Feb 15;65(4): 615-20.
  3. Zakrzewska JM, Forssel H, Glenny AM. Interventions for the treatment of burning mouth syndrome. The Cochrane Database of Systematic reviews, Issue 1, 2005.
  4. Torgerson RR. Burning mouth syndrome. Dermatol Ther. 2010 May-Jun;23(3):291-8.
  5. de Moraes M, do Amaral Bezerra BA, da Rocha Neto PC, de Oliveira Soares AC, Pinto LP, de Lisboa Lopes Costa A. Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. J Oral Pathol Med.2012 Apr;41 (4):281-7.
  6. Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. A double-blind study on clonazepam in patients with burning mouth syndrome. Laryngoscope. 2012 Apr;122(4):813-6.
  7. Lauria G, Majorana A, Borgna M, Lombardi R, Penza P, Padovani A, Sapelli P. Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome. Pain. 2005 Jun;115(3):332-7.
  8. Yilmaz Z, Renton T, Yiangou Y, Zakrzewska J, Chessell IP, Bountra C, Anand P. Burning mouth syndrome as a trigeminal small fibre neuropathy: Increased heat and capsaicin receptor TRPV1 in nerve fibres correlates with pain score. J Clin Neurosci. 2007 Sep;14(9):864-71.
  9. Hagelberg N, Jääskeläinen SK, Martikainen IK, Mansikka H, Forssell H, Scheinin H, Hietala J, Pertovaara A. Striatal dopamine D2 receptors in modulation of pain in humans: a review. Eur J Pharmacol. 2004 Oct 1;500(1-3):187-92.
  10. Hagelberg N, Forssell H, Rinne JO, Scheinin H, Taiminen T, Aalto S, Luutonen S, Nagren K, Jaaskelainen S. Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain. 2003 Jan;101(1-2):149-54.
  11. Drugan RC, Holmes PV. Central and peripheral benzodiazepine receptors: involvement in an organism's response to physical and psychological stress. Neurosci Biobehav Rev. 1991 Summer;15(2): 277-98.
  12. Mihic SJ, Whiting PJ, Klein RL, Wafford KA, Harris RA. A single amino acid of the human gammaaminobutyric acid type A receptor gamma 2 subunit determines benzodiazepine efficacy. J Biol Chem 1994;269:32768-73.
  13. EM Sellers, JM Khanna. Anxiolytics, hypnotics, and sedatives. H Kalant, W Roschlau (Eds.), Principles of medical pharmacology., Toronto, 1989, BC Decker Publisher., pp. 255-264
  14. WM Burnham. Antiseizure drugs (anticonvulsants). H Kalant, W Roschlau (Eds.), Principles of medical pharmacology., Toronto, 1989, BC Decker Publisher., pp. 203-213.
  15. Gremeau-Richard C, Woda A, Navez ML, Attal N, Bouhassira D, Gagnieu MC, Laluque JF, Picard P, Pionchon P, Tubert S. Topical clonazepam in stomatodynia: a randomised placebo-controlled study. Pain. 2004 Mar;108(1-2):51-7.
  16. 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 Nov;86(5):557-61.
  17. Tenn CC, Niles LP. Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum. Neuropharmacology. 1997 Nov-Dec;36(11 -12):1659-63.
  18. Woda A, Pionchon P. A unified concept of idiopathic orofacial pain: pathophysiologic features. J Orofac Pain. 2000 Summer;14(3):196-212.
  19. Dalezios Y, Matsokis N. Brain benzodiazepine binding in aged rats. Neurochem Int. 1998 Feb;32(2):213-7.
  20. Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86.
  21. American Dental Association status report on the occurrence of galvanic corrosion in the mouth and its potential effects. Council on Dental Materials, instruments, and Equipment. J Am Dent Assoc 1987;15:783-7.
  22. Bork K, Hoede N, Korting GW, Burgdorf W, Young S. Diseases of the oral mucosa and the lips. 2nd ed. Philadelphia: W. B Saunders; 1993 . p. 20-3.
  23. Avcu N, Kanli A. The prevalence of tongue lesions in 5150 Turkish dental outpatients. Oral Dis. 2003 Jul;9(4):188-95.
  24. Kullaa-Mikkonen A. Familial study of fissured tongue. Scand J Dent Res. 1988 Aug;96(4):366-75.
  25. Ching V, Grushka M, Darling M, Su N. Increased prevalence of geographic tongue in burning mouth complaints: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Aug 15.
  26. Siverman S, Eversole L, Truelove E. Essential of Oral medicine. BC Decker Inc.; 2001 . p . 335.
  27. van Joost T, van Ulsen J, van Loon LA. Contact allergy to denture materials in the burning mouth syndrome. Contact Dermatitis. 1988 Feb;18(2):97-9.

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