Burning mouth syndrome (BMS) is defined as a chronic, idiopathic, burning discomfort or pain in the context of clinically normal mucosa. BMS generally involves the oral mucosa, primarily the tongue, lips, hard palate, alveolar ridges, mouth floor, and cheeks. A burning sensation is the defining characteristic, but this may be accompanied by paraesthesia, xerostomia, and altered taste or smell.1 Prevalence studies show inconsistent results in the general population, ranging between 1% and 40%.2 Women who are post- or perimenopausal have the highest risk for BMS.3 The illness is usually diagnosed by dentists and general practitioners based on history and exclusion of other possible diseases. Patients diagnosed with BMS tend to have more anxiety and depressive symptoms or major depression. Social phobia, specific phobia, panic disorder, as well as neurotic, fearful, and obsessive-compulsive personality disorders have been associated with BMS.4 Despite the evidence of the relationship between BMS and psychiatric disorders, previous studies have not shown strong causality among them.5 One common underlying biological characteristic is low levels of dopamine neurotransmitter in the nigro-striatal pathway, which could be deemed as a potential common risk factor among patients with BMS and other psychiatric disorders, including several personality disorders.3,4 Antidepressants, analgesics, antiepileptics, antifungals, antibacterials, sialagogues, antihistamines, anxiolytics, and antipsychotics, as well as vitamin, mineral, and hormonal replacements have been shown to have beneficial effects in the treatment of patients with BMS.6 This article presents the case of a patient with primary BMS case who had a response after a low dose of aripiprazole was added to current treatment with duloxetine.
A 43-year-old man presented to our psychiatry outpatient clinic because of a persistent burning feeling in his tongue for the prior 6 months. The patient stated that 14 months ago he had started taking 30 mg daily of duloxetine for treatment of major depression. He first consulted with his primary care doctor and was diagnosed with atypical odontalgia and idiopathic orofacial pain. The doctor prescribed pain killers and anti-inflammatory drugs for his complaints. After 1 month, he was referred to an internal medicine specialist because of the persistent symptoms. The internal medicine specialist evaluated the patient with laboratory tests including blood morphology, biochemistry, serology, and hormone and vitamin levels. Laboratory results were normal, and additional intra- and extra-oral examinations of the patient were normal as well. The internal medicine specialist prescribed both a benzodiazepine and topical corticosteroid to provide relief of the patient's symptoms of idiopathic orofacial pain. After 2 months of taking these medications, the patient did not experience any improvement in his symptoms. He was then referred to an infectious disease specialist for additional examination. The patient was prescribed antibiotics, but he did not take the medication properly. Eventually, he discontinued the antibiotics and decided to see an otorhinolaryngologist.
The otorhinolaryngologist diagnosed the patient with BMS and referred him to our psychiatry outpatient clinic for the possible link between his complaints and mental disturbance. According to our psychiatric evaluation, the patient's history, and his stable antidepressant treatment, we concluded that the patient had been in a remission period for depression for the previous 8 months. During the psychiatric examination, the patient had a Hamilton Depression Scale score of 5. We ordered laboratory tests for him again, and we consulted with the patient's dentist. The patient's laboratory results were normal, as was his oral examination. Due to the lack of evidence for identifying the etiology of the pain and burning feeling on the patient's tongue, we considered BMS as the primary diagnosis with the otorhinolaryngologist's cooperation. The patient felt pain superficially in the oral mucosa along with the burning feeling, which had been recurring daily for more than 2 hours per day for more than 3 months. Additionally, his oral mucosa had normal appearance and no abnormality was found in clinical examination, including (clinical) sensory testing. According to the International Headache Society criteria,7 because these symptoms and findings could not be better accounted for by another diagnosis (eg, Sjögren syndrome, diabetes, mucosal erosive lesions, Candida infection) we diagnosed the patient with primary BMS. We used the short-form McGill Pain Questionnaire (SF-MPQ) for our follow-up. The patient had a score of 38, which is indicative of severe pain.
Treatment and Management
We increased the patient's dose of duloxetine to 60 mg daily for his BMS symptoms, but after 4 weeks of treatment there was no beneficial effect. Additionally, we observed side effects of sedation, so we decreased the dose to 30 mg daily and added 1 mg daily of aripiprazole oral solution to his treatment. Within 10 days, his SF-MPQ score decreased to 20. We gradually increased the dose of aripiprazole to 2.5 mg until his SF-MPQ score decreased to 3, which meant all of his BMS symptoms had disappeared in a 1-month period. We observed the patient for 6 months afterwards at 1-month intervals, and aripiprazole treatment was lowered gradually in the last 2 months before discontinuation. He continued his antidepressant treatment for 1 more year and there was no sign of BMS during this time.
We documented the case of a patient who experienced primary BMS while taking antidepressant medication for major depression. BMS is a complex disease that is difficult to diagnose and treat effectively because of its uncertain pathogenesis. The accurate diagnosis is based on the exclusion of the other potential diseases that overlap with the symptoms of BMS.8 There are several possible causes for BMS, such as reduced nigro-striatal dopamine levels, nerve degenerations, or sensorial neuropathies.9 Most BMS patients exhibit anxiety and depression and show relief from pain after administration of suitable psychotropic medications such as antidepressants. However, there are contrary findings regarding whether depression and anxiety are primary or secondary events to BMS. Moreover some studies could not find any association between BMS and high levels of psychological stress.10 Also, it was emphasized that among most cases, the presence of a psychiatric illness can be considered as a comorbid condition or a consequence, and not the cause of BMS itself.4 It was recommended that the onset of psychological disorders preceding the onset of pain symptoms might be a good indicator for identifying the etiology of BMS.4
In our patient, there was no sign of active depression and it had not overlapped with initiation of BMS. His BMS symptoms started 8 months after the emergence of his depression. Patients with BMS have shown a benefit with systemic regimens of antidepressants and anxiolytics;11 however, treatment management of this syndrome is still not satisfactory, and there is no absolute cure.12 Additionally, antidepressant medications are commonly used in BMS because of their analgesic activity, regardless of the presence of psychiatric comorbidity.13 Our patient had tried various medications that were prescribed by different specialists and he had not obtained any effect. According to the literature, duloxetine treatment was found to be effective in some cases diagnosed with BMS,8 so we maintained the treatment with duloxetine at a dose of 60 mg daily at first. After waiting for an adequate amount of time to obtain some benefit with that treatment, we decided to lower the dose because of the side effect of sedation and to add a low-dose antipsychotic that was reported to have greater effect in patients with BMS. Eventually, the patient's symptoms disappeared with the addition of aripiprazole. The literature shows that there are some treatment-resistant cases of BMS treated successfully with low-dose aripiprazole.11
We concluded that the treatment with aripirazole alone might improve BMS symptoms because the other medications had not shown any effect with a normal dose. An effective approach to treatment of patients with antidepressant-resistant BMS should take into account supportive care. The main aim of supportive care is to improve the patient's quality of life by reducing his or her pain.9 Aripiprazole may be one of the candidates for new treatment options for maintaining this supportive care. Studies that are searching for the underlying mechanisms of BMS hypothesize that dopamine regulates the pain-processing systems via opioid receptors and that potential hypofunction in dopaminergic systems through basal ganglia may cause BMS.11 Aripiprazole seems to have a unique antipsychotic effect that presents potent partial agonist activity at dopamine D2 receptors.14 Thus, it is possible that aripiprazole improved the symptoms of BMS in this patient by its action at the D2 receptor profile. Mounting evidence here seems to support treatment of BMS with a low dose of aripiprazole.
- Zakrzewska JM, Forssell H, Glenny A. Interventions for the treatment of burning mouth syndrome. Cochrane Database Syst Rev. 2005;(1):CD002779. https://doi.org/10.1002/14651858.CD002779.pub2 PMID:15674897
- 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. https://doi.org/10.1111/bjd.13613 PMID: doi:10.1111/bjd.13613 [CrossRef]
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- Taiminen T, Kuusalo L, Lehtinen L, et al. Psychiatric (axis I) and personality (axis II) disorders in patients with burning mouth syndrome or atypical facial pain. Scand J Pain. 2011;2(4):155–160. https://doi.org/10.1016/j.sjpain.2011.06.004 PMID: doi:10.1016/j.sjpain.2011.06.004 [CrossRef]
- Zilli C, Brooke RI, Lau CL, Merskey H. Screening for psychiatric illness in patients with oral dysesthesia by means of the General Health Questionnaire—twenty-eight item version (GHQ-28) and the Irritability, Depression and Anxiety Scale (IDA). Oral Surg Oral Med Oral Pathol.1989;67(4):384–389. https://doi.org/10.1016/0030-4220(89)90378-2 PMID: doi:10.1016/0030-4220(89)90378-2 [CrossRef]2726202
- 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(5)(suppl 1):S21–S25. https://doi.org/10.4103/0975-7406.137255 PMID: doi:10.4103/0975-7406.137255 [CrossRef]25210377
- Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia.2013;33(9):629–808. https://doi.org/10.1177/0333102413485658 PMID: doi:10.1177/0333102413485658 [CrossRef]23771276
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- Kim Y-D, Lee J-H, Shim J-H. Duloxetine in the treatment of burning mouth syndrome refractory to conventional treatment: a case report. J Int Med Res. 2014;42(3):879–883. https://doi.org/10.1177/0300060514527913 PMID: doi:10.1177/0300060514527913 [CrossRef]24743872
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- Umezaki Y, Takenoshita M, Toyofuku A. Low-dose aripiprazole for refractory burning mouth syndrome. Neuropsychiatr Dis Treat. 2016;12:1229–1231. https://doi.org/10.2147/NDT.S94426 PMID: doi:10.2147/NDT.S94426 [CrossRef]27279742
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