A systematic review of randomized trials for the treatment of burning mouth syndrome

https://doi.org/10.1016/j.jpsychores.2016.05.001Get rights and content

Highlights

  • BMS is a poorly-understood chronic pain disorder that affects up to 15% of people.

  • The results of previous systematic reviews have generally been equivocal.

  • Alpha-lipoic acid, capsaicin & clonazepam show modest benefit in the 1st two months.

  • Psychotherapy resulted in significant improvement in one study.

  • Conclusions are limited by study quality, short follow-up and low power.

Abstract

Objectives

Burning mouth syndrome (BMS) is characterized by burning of the oral mucosa in the absence of underlying dental or medical causes. The results of previous systematic reviews have generally been equivocal. However, findings for most interventions are based on searches of 5–10 years ago. This study therefore updates previous searches of randomized controlled trials (RCTs) for pain as assessed by Visual Analogue Scales (VAS). Secondary outcomes included quality of life, mood, taste and salivary flow.

Methods

A search of MEDLINE and Embase up to 2016.

Results

24 RCTs were identified. Meta-analyses were impossible because of wide variations in study method and quality. The commonest interventions were alpha-lipoic acid (ALA) (8 comparisons), capsaicin or an analogue (4 comparisons), clonazepam (3 comparisons) and psychotherapy (2 comparisons). ALA and capsaicin led to significantly greater improvements in VAS (4 studies each), as did clonazepam (all 3 studies), at up to two month follow-up. However, capsaicin led to prominent dyspepsia. Psychotherapy significantly improved outcomes in one study at two and 12 month follow-up. Catauma and tongue-protectors also showed promise (one study each). There were no significant differences in any of the secondary outcomes except in the one study of tongue protectors.

Conclusions

At least in some studies and for some outcomes, ALA, clonazepam, capsaicin and psychotherapy may show modest benefit in the first two months. However, these conclusions are limited by generally short follow-up periods, high study variability and low participant numbers. Further RCTs with follow-up of at least 12 months are indicated.

Introduction

There is a strong interaction between oral and mental health. In one direction, several psychiatric disorders such as schizophrenia, bipolar affective and eating disorders can lead to poor oral health because of poor oral hygiene, sugary drinks, barriers to accessing health care, chronic medical conditions, poor nutrition and comorbid substance misuse [1], [2], [3].

In the other direction, perception of dental pain may be exacerbated by someone's mental state, regardless of the degree of oral pathology. One example is burning mouth syndrome (BMS), a somatic symptom disorder characterized by a burning sensation in clinically healthy oral mucosa [4].

BMS is a poorly-understood but important chronic pain disorder that affects more than 1 million people in the United States [5]. BMS may be classified into three types [6]. In Type 1, patients are free of pain on waking but experience increasing symptoms as the day goes on. About a third of patients have this type of disorder and this is generally associated with organic disorders such as nutritional deficiency, auto-immune conditions and diabetes mellitus. In Type 2, patients have continuous pain throughout the day; this type accounts for 55% of patients and has the strongest association with psychological disorders [4]. In Type 3, patients have intermittent symptoms with pain-free periods during the day. These constitute 10% of patients with BMS and are associated with allergic reactions.

An alternative classification involves defining BMS as primary or secondary [7]. Patients with a primary or idiopathic BMS present with stinging or burning in the mouth, accompanied by a clinically normal oral mucosa with the absence of medical or dental diseases. By contrast, in patients with secondary BMS, symptoms arise from local or systemic organic conditions such as dry mouth, oral infections, autoimmune disorders, nutritional deficiencies, allergies, gastro-oesophageal reflux, medication side-effects, and some endocrine disorders.

Uncertainty concerning the diagnostic criteria for BMS means that it is difficult to estimate the prevalence of the disorder with figures of between 0.7 and 4.6% in the general population [6]. However, estimates for the broader syndrome have been as high as 15% [8]. It is more common among older people and women [6].

While treatment of secondary BMS is directed to treating the underlying organic cause, a wide range of interventions have been proposed for primary BMS [9]. Of these the most common are anti-oxidants or vitamins, capsaicin, anaesthetic agents and clonazepam [6], [9], [10]. Many are used both systematically and topically. Each of these will be considered in turn.

Alpha-lipoic acid (ALA) is a mitochondrial coenzyme with both antioxidant and neuroprotective effects. ALA may also stimulate the production of neural growth factors [6]. Capsaicin is responsible for the burning sensation experienced with hot chili pepper, and acts on the sensory afferent neuron [6], [10]. It binds to TRPV1, a potent calcium channel-specific receptor, thereby inactivating neuronal responses to heat [11]. Prolonged exposure depletes TRPV1 leading to desensitization of pain receptors [11]. Topical capsaicin can also be used as a desensitizing agent or analgesic although its taste reduces acceptability [6], [10].

Clonazepam acts as an agonist of gamma-amino butyric acid (GABA) receptors. In oral form, it leads to central nervous system inhibition resulting in an anticonvulsant action, sedation, muscular relaxation, and tranquilisation [6], [10]. Topically, clonazepam can reduce burning symptoms without the adverse effects of systemic use.

Lidocaine is commonly used as a local anaesthetic in dental clinics while benzydamine hydrochlorate has both anaesthetic and anti-inflammatory effects [6], [10]. These two agents can be used as a mouthwash to lessen the pain or burning symptom in BMS. However, the short duration of the analgesic effect limits their efficacy.

Additional physical treatments have included antidepressants, antipsychotics, St John's Wort, Aloe vera and tongue protectors [6], [10]. Because of the strong psychological component of the illness, psychotherapy has also been tried [6], [10].

The results of previous systematic reviews of possible interventions were equivocal [10], [11], [12]. However, they were based on searches of 5 to 10 years ago. The one exception was a systematic review that was restricted to clonazepam [13]. This study therefore updates previous searches of randomized controlled trials (RCTs) of all available treatments where the primary outcome was pain intensity.

Section snippets

Method

The review was registered with PROSPERO, an international database of prospectively registered systematic reviews in health and social care based in the United Kingdom (Registration number: CRD42016032778) [14]. In addition, we followed recommendations for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement including background, search strategy, methods, results, discussion and conclusions [15].

Results

We found 295 citations of interest in the initial electronic searches, of which 87 abstracts were screened. Of these, 35 full-text papers were potentially relevant and assessed for eligibility. Thirteen papers were excluded for reasons listed in Fig. 1. Two additional papers were found from the reference lists of other papers from the database search. This left 24 papers (Fig. 1). Participants were predominately females of older age.

The most common interventions were alpha-lipoic acid (ALA) (8

Discussion

Burning mouth syndrome is a poorly-understood chronic pain disorder that results in significant distress. ALA, clonazepam, capsaicin and psychotherapy showed modest benefit in the first two months at least in some studies and for some outcomes. Evidence for longer term outcomes was more limited. Catauma, tongue-protectors and clonazepam also showed promise. However, these conclusions are limited by short follow-up periods, marked variability in study methods and quality, and low participant

Competing interest statement

The authors have no competing interests to report.

Conflict of interest statement

There are no actual or potential conflicts of interest related to this manuscript.

Acknowledgements

Emily Sawyer was supported by the University of Queensland Summer Research programme.

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