Dental and Medical Problems

Dent Med Probl
Index Copernicus (ICV 2021) – 132.50
MEiN – 70 pts
CiteScore (2021) – 2.0
JCI (2021) – 0.5
Average rejection rate (2022) – 79.69%
ISSN 1644-387X (print)
ISSN 2300-9020 (online)
Periodicity – quarterly

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Dental and Medical Problems

2022, vol. 59, nr 4, October-December, p. 603–616

doi: 10.17219/dmp/152646

Publication type: review

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Khemiss M, Chaabouni D, Ben Khaled R, Ben Khélifa M. Place of placebo therapy in the treatment of burning mouth syndrome: A systematic review. Dent Med Probl. 2022;59(4):603–616. doi:10.17219/dmp/152646

Place of placebo therapy in the treatment of burning mouth syndrome: A systematic review

Mehdi Khemiss1,A,B,C,D,E,F, Dorra Chaabouni1,A,B,C,D,E,F, Rim Ben Khaled1,A,B,C,D,E,F, Mohamed Ben Khélifa1,D,E,F

1 Department of Dental Medicine, Fattouma Bourguiba University Hospital, Monastir, Tunisia

Abstract

Burning mouth syndrome (BMS) is defined as an idiopathic orofacial pain with intraoral burning or dysesthesia. This systematic review aimed to analyze the scientific literature with regard to the effectiveness of placebo therapy in patients with BMS. A literature search was conducted through the PubMed-indexed journals within MEDLINE®, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Trip databases from their inception to May 31, 2022. The search terms were defined by combining (medical subject headings (MeSH) terms OR keywords) “burning mouth syndrome” AND (MeSH terms OR keywords) “placebo”. Methodological quality assessments were performed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal tool to attribute scores from 1 to 11 to the selected studies. The literature search, study selection and data extraction were carried out by 2 authors. Disagreements between the authors were resolved by the 3rd author, if necessary. A total of 44 articles met the inclusion criteria. After assessing full-text articles for eligibility, 20 articles were excluded. Consequently, 24 articles were retained. A total of 21 studies included in this systematic review had a low score of bias. In 13 studies, a positive response to placebo was noted. Among them, 7 showed a placebo response indistinguishable from active treatment. These changes were more pronounced in patients receiving placebo therapy compared to active treatment in 1 study. Placebo therapy may occasionally be beneficial and ethically acceptable for patients with BMS. To get stronger evidence for the use of a placebo, future studies with standardized methodology and outcomes are required.

Key words

pain, trigeminal, stomatodynia, placebo effect

References (79)

  1. International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia. 2020;40(2):129–221. doi:10.1177/0333102419893823
  2. Kohorst JJ, Bruce AJ, Torgerson RR, Schenck LA, Davis MDP. The prevalence of burning mouth syndrome: A population-based study. Br J Dermatol. 2015;172(6):1654–1656. doi:10.1111/bjd.13613
  3. Aravindhan R, Vidyalakshmi S, Kumar MS, Satheesh C, Balasubramanium AM, Prasad VS. Burning mouth syndrome: A review on its diagnostic and therapeutic approach. J Pharm Bioallied Sci. 2014;6(Suppl 1):21–25. doi:10.4103/0975-7406.137255
  4. Bergdahl M, Bergdahl J. Burning mouth syndrome: Prevalence and associated factors. J Oral Pathol Med. 1999;28(8):350–354. doi:10.1111/j.1600-0714.1999.tb02052.x
  5. Grushka M, Epstein JB, Gorsky M. Burning mouth syndrome. Am Fam Physician. 2002;65(4):615–620. PMID:11871678.
  6. de la Fuente-Fernández R, Stoessl AJ. The placebo effect in Parkinson’s disease. Trends Neurosci. 2002;25(6):302–306. doi:10.1016/s0166-2236(02)02181-1
  7. Patton LL, Siegel MA, Benoliel R, De Laat A. Management of burning mouth syndrome: Systematic review and management recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(S39):e1–e13. doi:10.1016/j.tripleo.2006.11.009
  8. Fischoff DK, Spivakovsky S. Little evidence to support or refute interventions for the management of burning mouth syndrome. Evid Based Dent. 2017;18(2):57–58. doi:10.1038/sj.ebd.6401244
  9. Mashyakhy M, Alkahtani A, Abumelha AS, et al. Taurine augments telomerase activity and promotes chondrogenesis in dental pulp stem cells. J Pers Med. 2021;11(6):491. doi:10.3390/jpm11060491
  10. Balaji TM, Varadarajan S, Jagannathan R, et al. Melatonin as a topical/systemic formulation for the management of periodontitis: A systematic review. Materials (Basel). 2021;14(9):2417. doi:10.3390/ma14092417
  11. Reyad AA, Mishriky R, Girgis E. Pharmacological and non-pharmacological management of burning mouth syndrome: A systematic review. Dent Med Probl. 2020;57(3):295–304. doi:10.17219/dmp/120991
  12. Pollo A, Benedetti F. The placebo response: Neurobiological and clinical issues of neurological relevance. Prog Brain Res. 2009;175:283–294. doi:10.1016/S0079-6123(09)17520-9
  13. Cavanna AE, Strigaro G, Monaco F. Brain mechanisms underlying the placebo effect in neurological disorders. Funct Neurol. 2007;22(2):89–94. PMID:17637211.
  14. Al-Maweri SA, Javed F, Kalakonda B, AlAizari NA, Al-Soneidar W, Al-Akwa A. Efficacy of low level laser therapy in the treatment of burning mouth syndrome: A systematic review. Photodiagnosis Photodyn Ther. 2017;17:188–193. doi:10.1016/j.pdpdt.2016.11.017
  15. Alqahtani SS. The efficiency of alpha-lipoic acid in the treatment of burning mouth syndrome: A systematic review. Eur Rev Med Pharmacol Sci. 2021;25(21):6585–6591. doi:10.26355/eurrev_202111_27101
  16. Cronshaw M, Parker S, Anagnostaki E, Mylona V, Lynch E, Grootveld M. Photobiomodulation dose parameters in dentistry: A systematic review and meta-analysis. Dent J (Basel). 2020;8(4):114. doi:10.3390/dj8040114
  17. de Souza IF, Mármora BC, Rados PV, Visioli F. Treatment modalities for burning mouth syndrome: A systematic review. Clin Oral Investig. 2018;22(5):1893–1905. doi:10.1007/s00784-018-2454-6
  18. Kisely S, Forbes M, Sawyer E, Black E, Lalloo R. A systematic review of randomized trials for the treatment of burning mouth syndrome. J Psychosom Res. 2016;86:39–46. doi:10.1016/j.jpsychores.2016.05.001
  19. Liu YF, Kim Y, Yoo T, Han P, Inman JC. Burning mouth syndrome: A systematic review of treatments. Oral Dis. 2018;24(3):325–334. doi:10.1111/odi.12660
  20. Ślebioda Z, Lukaszewska-Kuska M, Dorocka-Bobkowska B. Evaluation of the efficacy of treatment modalities in burning mouth syndrome – A systematic review. J Oral Rehabil. 2020;47(11):1435–1447. doi:10.1111/joor.13102
  21. Tan HL, Smith JG, Hoffmann J, Renton T. A systematic review of treatment for patients with burning mouth syndrome. Cephalalgia. 2022;42(2):128–161. doi:10.1177/03331024211036152
  22. Yan Z, Ding N, Hua H. A systematic review of acupuncture or acupoint injection for management of burning mouth syndrome. Quintessence Int. 2012;43(8):695–701. PMID:23034422.
  23. Zhang W, Hu L, Zhao W, Yan Z. Effectiveness of photobiomodulation in the treatment of primary burning mouth syndrome – A systematic review and meta-analysis. Lasers Med Sci. 2021;36(2):239–248. doi:10.1007/s10103-020-03109-9
  24. Kuten-Shorrer M, Kelley JM, Sonis ST, Treister NS. Placebo effect in burning mouth syndrome: A systematic review. Oral Dis. 2014;20(3):e1–e6. doi:10.1111/odi.12192
  25. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–e34. doi:10.1016/j.jclinepi.2009.06.006
  26. Ma LL, Wang YY, Yang ZH, Huang D, Weng H, Zeng XT. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better? Mil Med Res. 2020;7(1):7. doi:10.1186/s40779-020-00238-8
  27. Bardellini E, Amadori F, Conti G, Majorana A. Efficacy of the photobiomodulation therapy in the treatment of the burning mouth syndrome. Med Oral Patol Oral Cir Bucal. 2019;24(6):e787–e791. doi:10.4317/medoral.23143
  28. Alves MB, Motta ACF, Messina WC, Migliari DA. Saliva substitute in xerostomic patients with primary Sjögren’s syndrome: A single-blind trial. Quintessence Int. 2004;35(5):392–396. PMID:15130080.
  29. Bergdahl J, Anneroth G, Perris H. Cognitive therapy in the treatment of patients with resistant burning mouth syndrome: A controlled study. J Oral Pathol Med. 1995;24(5):213–215. doi:10.1111/j.1600-0714.1995.tb01169.x
  30. Vukoja D, Alajbeg I, Vučićević Boras V, Brailo V, Alajbeg IZ, Andabak Rogulj A. Is effect of low-level laser therapy in patients with burning mouth syndrome result of a placebo? Photomed Laser Surg. 2011;29(9):647–648. doi:10.1089/pho.2011.3005
  31. López-Jornet P, Camacho-Alonso F, Molino-Pagan D. Prospective, randomized, double-blind, clinical evaluation of Aloe vera Barbadensis, applied in combination with a tongue protector to treat burning mouth syndrome. J Oral Pathol Med. 2013;42(4):295–301. doi:10.1111/jop.12002
  32. Talal N, Quinn JH, Daniels TE. The clinical effects of electrostimulation on salivary function of Sjögren’s syndrome patients. A placebo controlled study. Rheumatol Int. 1992;12(2):43–45. doi:10.1007/BF00300975
  33. Femiano F. Burning mouth syndrome (BMS): An open trial of comparative efficacy of alpha-lipoic acid (thioctic acid) with other therapies. Minerva Stomatol. 2002;51(9):405–409. PMID:12473978.
  34. Alpöz E, Güneri P, Onder G, Cankaya H, Kabasakal Y, Köse T. The efficacy of Xialine in patients with Sjögren’s syndrome: A single-blind, cross-over study. Clin Oral Investig. 2008;12(2):165–172. doi:10.1007/s00784-007-0159-3
  35. Femiano F, Gombos F, Scully C, Busciolano M, De Luca P. Burning mouth syndrome (BMS): Controlled open trial of the efficacy of alpha-lipoic acid (thioctic acid) on symptomatology. Oral Dis. 2000;6(5):274–277. doi:10.1111/j.1601-0825.2000.tb00138.x
  36. Silvestre FJ, Silvestre-Rangil J, Tamarit-Santafé C, Bautista D. Application of a capsaicin rinse in the treatment of burning mouth syndrome. Med Oral Patol Oral Cir Bucal. 2012;17(1):e1–e4. doi:10.4317/medoral.17219
  37. Loldrup D, Langemark M, Hansen HJ, Olesen J, Bech P. Clomipramine and mianserin in chronic idiopathic pain syndrome. A placebo controlled study. Psychopharmacology (Berl). 1989;99(1):1–7. doi:10.1007/BF00634443
  38. Treldal C, Jacobsen CB, Mogensen S, et al. Effect of a local anesthetic lozenge in relief of symptoms in burning mouth syndrome. Oral Dis. 2016;22(2):123–131. doi:10.1111/odi.12386
  39. Zakrzewska JM, Forssell H, Glenny AM. Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev. 2005;(1):CD002779. doi:10.1002/14651858.CD002779.pub2
  40. Zakrzewska JM, Glenny AM, Forssell H. Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev. 2001;(3):CD002779. doi:10.1002/14651858.CD002779
  41. 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. Med Oral Patol Oral Cir Bucal. 2011;16(5):e635–e640. doi:10.4317/medoral.16942
  42. Eccleston C, Hearn L, Williams AC. Psychological therapies for the management of chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2015;2015(10):CD011259. doi:10.1002/14651858.CD011259.pub2
  43. Fischoff D, Spivakovsky S. Are pharmacological treatments for oro-facial pain effective? Evid Based Dent. 2018;19(1):28–29. doi:10.1038/sj.ebd.6401294
  44. Ottaviani G, Rupel K, Gobbo M, et al. Efficacy of ultramicronized palmitoylethanolamide in burning mouth syndrome-affected patients: A preliminary randomized double-blind controlled trial. Clin Oral Investig. 2019;23(6):2743–2750. doi:10.1007/s00784-018-2720-7
  45. Grigoleit HG, Grigoleit P. Peppermint oil in irritable bowel syndrome. Phytomedicine. 2005;12(8):601–606. doi:10.1016/j.phymed.2004.10.005
  46. McMillan R, Forssell H, Buchanan JA, Glenny AM, Weldon JC, Zakrzewska JM. Interventions for treating burning mouth syndrome. Cochrane Database Syst Rev. 2016;11(11):CD002779. doi:10.1002/14651858.CD002779.pub3
  47. Petruzzi M, Lauritano D, De Benedittis M, Baldoni M, Serpico R. Systemic capsaicin for burning mouth syndrome: Short-term results of a pilot study. J Oral Pathol Med. 2004;33(2):111–114. doi:10.1111/j.1600-0714.2004.0194n.x
  48. Carbone M, Pentenero M, Carrozzo M, Ippolito A, Gandolfo S. Lack of efficacy of alpha-lipoic acid in burning mouth syndrome: A double-blind, randomized, placebo-controlled study. Eur J Pain. 2009;13(5):492–496. doi:10.1016/j.ejpain.2008.06.004
  49. Valenzuela S, Pons-Fuster A, López-Jornet P. Effect of a 2% topical chamomile application for treating burning mouth syndrome: A controlled clinical trial. J Oral Pathol Med. 2016;45(7):528–533. doi:10.1111/jop.12412
  50. López-Jornet P, Camacho-Alonso F, Leon-Espinosa S. Efficacy of alpha lipoic acid in burning mouth syndrome: A randomized, placebo-treatment study. J Oral Rehabil. 2009;36(1):52–57. doi:10.1111/j.1365-2842.2008.01914.x
  51. 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. Med Oral Patol Oral Cir Bucal. 2015;20(4):e435–e440. doi:10.4317/medoral.20410
  52. de Pedro M, López-Pintor RM, Casañas E, Hernández G. Effects of photobiomodulation with low-level laser therapy in burning mouth syndrome: A randomized clinical trial. Oral Dis. 2020;26(8):1764–1776. doi:10.1111/odi.13443
  53. Valenzuela S, Lopez-Jornet P. Effects of low-level laser therapy on burning mouth syndrome. J Oral Rehabil. 2017;44(2):125–132. doi:10.1111/joor.12463
  54. Spanemberg JC, Cherubini K, de Figueiredo MAZ, Gomes APN, Campos MM, Salum FG. Effect of an herbal compound for treatment of burning mouth syndrome: Randomized, controlled, double-blind clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(3):373–377. doi:10.1016/j.oooo.2011.09.005
  55. Varoni EM, Lo Faro AF, 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. J Oral Facial Pain Headache. 2018;32(2):178–188. doi:10.11607/ofph.1913
  56. Sardella A, Lodi G, Demarosi F, Tarozzi M, Canegallo L, Carrassi A. Hypericum perforatum extract in burning mouth syndrome: A randomized placebo-controlled study. J Oral Pathol Med. 2008;37(7):395–401. doi:10.1111/j.1600-0714.2008.00663.x
  57. Sardella A, Uglietti D, Demarosi F, Lodi G, Bez C, Carrassi A. Benzydamine hydrochloride oral rinses in management of burning mouth syndrome. A clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88(6):683–686. doi:10.1016/s1079-2104(99)70010-7
  58. Miziara ID, Filho BCA, Oliveira R, Rodrigues dos Santos RM. Group psychotherapy: An additional approach to burning mouth syndrome. J Psychosom Res. 2009;67(5):443–448. doi:10.1016/j.jpsychores.2009.01.013
  59. Cavalcanti DR, da Silveira FRX. Alpha lipoic acid in burning mouth syndrome – A randomized double-blind placebo-controlled trial. J Oral Pathol Med. 2009;38(3):254–261. doi:10.1111/j.1600-0714.2008.00735.x
  60. Femiano F, Gombos F, Scully C. Burning mouth syndrome: Open trial of psychotherapy alone, medication with alpha-lipoic acid (thioctic acid), and combination therapy. Med Oral. 2004;9(1):8–13. PMID:14704612.
  61. Femiano F, Scully C. Burning mouth syndrome (BMS): Double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. J Oral Pathol Med. 2002;31(5):267–269. doi:10.1034/j.1600-0714.2002.310503.x
  62. Gremeau-Richard C, Woda A, Navez ML, et al. Topical clonazepam in stomatodynia: A randomised placebo-controlled study. Pain. 2004;108(1–2):51–57. doi:10.1016/j.pain.2003.12.002
  63. Tammiala-Salonen T, Forssell H. Trazodone in burning mouth pain: A placebo-controlled, double-blind study. J Orofac Pain. 1999;13(2):83–88. PMID:10425979.
  64. Škrinjar I, Lončar Brzak B, Vidranski V, Vučićević Boras V, Rogulj AA, Pavelić B. Salivary cortisol levels and burning symptoms in patients with burning mouth syndrome before and after low level laser therapy: A double blind controlled randomized clinical trial. Acta Stomatol Croat. 2020;54(1):44–50. doi:10.15644/asc54/1/5
  65. Sugaya NN, da Silva ÉFP, Kato IT, Prates R, de Barros Gallo C, Pellegrini VD. Low intensity laser therapy in patients with burning mouth syndrome: A randomized, placebo-controlled study. Braz Oral Res. 2016;30(1):e108. doi:10.1590/1807-3107BOR-2016.vol30.0108
  66. Scardina GA, Casella S, Bilello G, Messina P. Photobiomodulation therapy in the management of burning mouth syndrome: Morphological variations in the capillary bed. Dent J (Basel). 2020;8(3):99. doi:10.3390/dj8030099
  67. Cano-Carrillo P, Pons-Fuster A, López-Jornet P. Efficacy of lycopene-enriched virgin olive oil for treating burning mouth syndrome: A double-blind randomised. J Oral Rehabil. 2014;41(4):296–305. doi:10.1111/joor.12147
  68. 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. Eur J Neurol. 2006;13(7):e6–e7. doi:10.1111/j.1468-1331.2006.01294.x
  69. Rodríguez de Rivera Campillo E, López-López J, Chimenos-Küstner E. Response to topical clonazepam in patients with burning mouth syndrome: A clinical study. Bull Group Int Rech Sci Stomatol Odontol. 2010;49(1):19–29. PMID:22750263.
  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(2):123–128. doi:10.1111/ger.12332
  71. Millum J, Grady C. The ethics of placebo-controlled trials: Methodological justifications. Contemp Clin Trials. 2013;36(2):510–514. doi:10.1016/j.cct.2013.09.003
  72. Hopewell S, Boutron I, Altman DG, Ravaud P. Incorporation of assessments of risk of bias of primary studies in systematic reviews of randomised trials: A cross-sectional study. BMJ Open. 2013;3(8):e003342. doi:10.1136/bmjopen-2013-003342
  73. Jørgensen L, Paludan-Müller AS, Laursen DRT, et al. Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: Overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews. Syst Rev. 2016;5:80. doi:10.1186/s13643-016-0259-8
  74. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63(S11):S240–S252. doi:10.1002/acr.20543
  75. Savage NW, Boras VV, Barker K. Burning mouth syndrome: Clinical presentation, diagnosis and treatment. Australas J Dermatol. 2006;47(2):77–81. doi:10.1111/j.1440-0960.2006.00236.x
  76. Greene CS, Goddard G, Macaluso GM, Mauro G. Topical review: Placebo responses and therapeutic responses. How are they related? J Orofac Pain. 2009;23(2):93–107. PMID:19492534.
  77. Finniss DG, Benedetti F. Mechanisms of the placebo response and their impact on clinical trials and clinical practice. Pain. 2005;114(1–2):3–6. doi:10.1016/j.pain.2004.12.012
  78. Meissner K, Bingel U, Colloca L, Wager TD, Watson A, Flaten MA. The placebo effect: Advances from different methodological approaches. J Neurosci. 2011;31(45):16117–16124. doi:10.1523/JNEUROSCI.4099-11.2011
  79. Stoessl AJ. Deception and the ethics of placebo. Int Rev Neurobiol. 2020;153:147–163. doi:10.1016/bs.irn.2020.03.030
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