Mouths on fire: Drug-induced burning mouth syndrome

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Mouths on fire: Drug-induced burning mouth syndrome
Mirella Giudice, BScPharm

Burning mouth syndrome (BMS) is defined as a chronic orofacial pain syndrome, without evidence of mucosal lesions and other clinical signs of disease or laboratory abnormalities.1,2 It is also known as scalded mouth syndrome, glossodynia, and stomatodynia.3 Patients with BMS complain of burning pain in the mouth, thirst, xerostomia, taste disturbances, and oral sensations of tingling or numbness.1,3 It is primarily the tongue that is affected, but symptoms may also involve the gums, palate, lips, insides of the cheeks, back of the mouth, and throat.1–3 Symptoms vary in intensity from mild to severe and are continually present but uncommon during sleep.2 According to a Canadian survey, the prevalence of BMS was estimated at 1.5%. The majority (75%) affected were women, and the median age was 50 years.1

Two types of BMS exist. Primary BMS is idiopathic; its etiology is not well defined but may be neuropathic in origin.1,2 Secondary BMS, now referred to as “burning mouth sensations,” is not a true form of BMS but rather symptoms of various conditions. Box 1 lists the various causes of secondary BMS. Multiple causes of BMS are found in over one-third of patients.1

Cases of drug-induced BMS in the literature are scant (Box 2). Of the implicated medications, angiotensin-converting enzyme (ACE) inhibitors are the most frequent. A literature search identified a total of 9 cases of ACE inhibitor-induced BMS (4 each with captopril and enalapril and 1 with lisinopril).4–9 Symptom onset varied from within 1 week to as long as 6 months after initiating therapy.5–7,9 In 2 reports, both involving captopril, symptoms appeared only after the dose was increased.9 The ACE inhibitor was discontinued in all but 2 cases. Symptoms generally resolved within 1 week; however, in 1 case, 18 days was needed for resolution.4–7,9 One patient was able to tolerate enalapril following a dose reduction while a second had symptom resolution despite continuing captopril.8,9 Two patients did not experience BMS with other ACE inhibitors.4,8 Symptoms recurred in the 2 patients who were rechallenged with the causative agent (1 each with captopril and enalapril).7,9

Reported cases of BMS exist with various other medications. Angiotensin-receptor blockers (ARBs) were implicated in 2 patients (1 each with eprosartan and losartan).10,11 Onset of symptoms was 3 weeks after starting therapy, with symptoms resolving within 1 to 2 weeks of stopping the ARB. In the case involving eprosartan, the patient had previously tolerated valsartan. A rechallenge with eprosartan resulted in recurrence of symptoms.10

Efavirenz was the probable cause of BMS in a 42-year-old female.12 Two weeks after initiating the drug, she developed BMS. Symptoms resolved within 1 week of switching antiretrovirals. Hormone replacement therapy (HRT) was reported to cause BMS in a 56-year-old female.13 Eight weeks after starting HRT, a dentist diagnosed her symptoms as BMS. Two weeks after stopping HRT, her symptoms had mostly resolved. She was not rechallenged. (Of note, BMS occurs most commonly in postmenopausal women. Studies examining the efficacy of HRT for BMS demonstrated conflicting results.)1 A cross-sectional study of 427 elderly patients found an association between anticoagulants and burning mouth.14 The types of anticoagulants used were not specified. Although chemotherapy is cited as a cause of BMS, no cases were identified in the literature.3 Finally, any medication that causes dry mouth can exacerbate BMS (e.g., anticholinergic agents).1,3

Antidepressants and benzodiazepines are recommended as treatment for BMS.1 Interestingly, these drug classes were reported to cause this condition in 2 separate case reports.15,16 Antidepressant-induced glossodynia occurred in a 56-year-old female with dysthymia and major depressive disorder.15 Trials with fluoxetine, sertraline, and venlafaxine all resulted in BMS. When rechallenged with fluoxetine, her symptoms recurred. Symptoms appeared to be dose-related for both fluoxetine and sertraline. This patient next tried citalopram, and her symptoms did not recur. In a second report, a 52-year-old woman was switched from alprazolam to clonazepam 0.5 mg twice a day for the management of panic and anxiety.16 Four weeks later, she developed symptoms of burning mouth that worsened with continued treatment. Halving the dose led to only partial symptom relief. Clonazepam was replaced with diazepam, and symptoms disappeared within 3 weeks. Because diazepam and other anxiolytics were ineffective, this patient was later rechallenged with clonazepam. After 2 weeks, symptoms recurred but again resolved within 2 to 3 weeks of stopping the drug.

Symptoms of burning mouth were also reported in conjunction with orolingual tardive dyskinesia (TD) in 9 patients on long-term antipsychotic therapy (this article classified metoclopramide as an antipsychotic).17 Six patients had a diagnosis of depression and/or anxiety. Symptoms appeared after 1 to 6 years of starting therapy, either within 6 months of, or concurrently with, the development of orolingual TD. Tetrabenazine and reserpine, agents used to treat TD, were the most effective drugs in relieving symptoms. Various analgesics proved mostly ineffective.

Patients presenting with BMS should be evaluated for secondary causes and treated accordingly (Box 1). Primary BMS should only be diagnosed after all possible causes of secondary BMS are ruled out.1 Nonpharmacologic treatment of BMS includes:

*Increasing fluid intake or using saliva substitutes if dry mouth is present
*Discontinuing the use of mouthwashes, chewing gum, and tobacco
*Avoiding acidic drinks
*Switching to an alternative brand of toothpaste that does not contain abrasive agents (such as Colgate Total and Oral-B)3

Medications used to treat both primary and secondary BMS include antidepressants (i.e., amitriptyline, trazodone, paroxetine, duloxetine), benzodiazepines (e.g., local or oral clonazepam, chlordiazepoxide), topical capsaicin, mexiletine, and anticonvulsants (e.g., gabapentin, pregabalin).1 In the above-mentioned cases of drug-induced BMS (excluding antipsychotics), none of these options were used. No specific treatment for drug-induced BMS was identified (other than symptoms occurring in the setting of orolingual TD). Decreasing the dose of the offending medication may result in symptom relief. However, switching to an alternative drug may be required.

Canadian Pharmacists Journal
Article: pp. 132–134