Commentary

Burning mouth syndrome is a diagnosis of exclusion used for oral mucosal burning or pain without identifiable dental or medical causes. It has been considered a syndrome because patients may also experience xerostomia and altered taste or smell. Recent studies have demonstrated that several neuropathic mechanisms (both central and peripheral changes) contribute to the pathophysiology of BMS. Anxiety, depression and personality disorders are often co-morbid psychiatric diagnoses in these patients. BMS is a common chronic condition that occurs more often in women. It has been shown to negatively affect quality of life, necessitating the need for studies investigating effective interventions.

This is an update of a previously reported review in 2005 that included nine trials. This review consists of 23 randomised controlled trials comparing any treatment against placebo. The authors were careful to review only studies that included patients with ruled-out identifiable causes of oral mucosal burning. A total of 1061 women (83%) and 221 men (17%) are reported to have participated in these studies.

The primary outcomes measured were symptom relief and changes in quality of life. The VAS scale as a measure of pain or burning was used in 17 of the studies. Other measures were used in the remaining studies. Only four studies directly assessed changes in quality of life, while three studies assessed depression or anxiety as secondary markers of quality of life. Since anxiety, depression and personality disorders are often co-morbid with BMS, it may be unrealistic to expect changes in quality of life in studies without psychological therapy, but it may help elucidate the relationship of pain to the psychological conditions.

The secondary outcomes evaluated were changes in taste, changes in dryness and adverse effects. Only two studies assessed changes in taste. There were no studies with quantitative data for changes in feeling of dryness.

The review categorises the treatment interventions into: antidepressants, antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical appliance, psychotherapy and topical treatments. Most of the interventions studied were selected based on treatments used for other types of neuropathic pain (clonazepam, gabapentin, alpha lipoic acid), Some interventions targeted increasing salivary flow (bethanachol, lactoperoxidase rinse, topical urea).

The authors suggest that one limitation of all of the studies reviewed was that other drugs within the same class as the drug investigated were not used as a comparison. It needs to be considered that some drugs used for the treatment of neuropathic pain are unique in their class. Gabapentin is an anticonvulsant that is commonly used to treat neuropathic pain, clonazepam is a benzodiazepine that is commonly used to treat neuropathic pain and capsaicin is a topical treatment for desensitization of peripheral nerves for the treatment of neuropathic pain. Alpha lipoic acid is a dietary supplement that has been previously been studied for the treatment of diabetic neuropathy. If BMS is a neuropathic pain it would necessitate studies of interventions that have been shown to be effective in other types of neuropathic pains. The authors even suggest in their conclusion that treatments that are established in the management of neuropathic pain conditions and psychological therapies should be considered for clinical trials in BMS.

Only placebo-controlled studies were included in this review. While such trials limit bias, placebo may also be a limitation when studying pain and could be the reason why there were only four long-term studies, none with systemic medications. According to the reviewers, about half of the studies had a high risk of attrition and selective reporting.

The review found some evidence of a benefit (very low quality) in short-term symptom relief for electromagnetic radiation, topical benzodiazepines, physical barriers and anticonvulsants. From the long-term effect data available, the review found some evidence for symptom relief (very low quality) from psychological therapies, capsaicin oral rinse (topical) and topical benzodiazepines.

Of the little data available for quality of life, the review found some evidence of short-term improvement from electromagnetic radiation. Findings for changes in taste and feeling of dryness were inconclusive. There was a low quality of evidence for adverse events for antidepressants and alpha lipoic acid, and insufficient evidence of adverse events for anticonvulsants and benzodiazepines. Adverse events were poorly or under reported for cholinergics, psychological therapies and electromagnetic radiation.

Overall the quality of the evidence assessed was very low for all interventions except physical barriers, which was assessed as low.

Ideally long term RCTs are needed to evaluate the effectiveness of neuropathic pain medications and psychological therapies for BMS. Long-term studies may be challenging and perhaps unethical when requiring retention of placebo-controlled patients who have been experiencing long term pain.