Dry mouth is a common side effect of certain medications, radiotherapy for head and neck cancer and diseases including Sjogren’s syndrome and rheumatoid arthritis. Often overlooked, dry mouth must be treated to prevent comorbidities like caries and dysphagia.
Xerostomia, also known as “dry mouth,” is a common but frequently overlooked condition that is typically associated with salivary gland hypofunction (SGH), which is the objective measurement of reduced salivary flow (Plemons et al 2014). Xerostomia and hyposalivation are two separate entities, xerostomia denoting the subjective feeling, the symptom, of dry mouth, while hyposalivation denotes the sign, a decreased saliva flow rate (Nederfors 2000).
In addition to its role in digestion, saliva serves several protective functions, including cleansing the oral cavity, facilitating oral processing and swallowing of food, protecting oral tissues against physical and microbial insults, maintaining a neutral pH and preventing demineralisation (Plemons et al 2014). When xerostomia is the result of a reduction in salivary flow, significant oral complications can occur (Guggenheimer and Moore 2003).
Although xerostomia often is a manifestation of impaired salivary gland function, it can occur with or without a noticeable decrease in saliva production (Plemons et al 2014). Clinicians may encounter symptoms of xerostomia among patients who take medications, have certain connective tissue or immunological disorders or have been treated with radiation therapy (Guggenheimer and Moore 2003).
Chronic xerostomia significantly increases the risk of experiencing dental caries, demineralisation, tooth sensitivity, candidiasis and other oral diseases that may affect quality of life negatively (Plemons et al 2014).
Aetiology and prevalence
Although information about the prevalence of xerostomia is lacking, it is known to be a more common complaint among geriatric and medically complex patients in particular (Navazesh 2017). The prevalence of xerostomia has been reported to be 24–27% in women and 18–21% in men in a European population (Anil et al 2014).
In Swedish institutionalised older people, the prevalence has been reported to be 20–72% (Anil et al 2014). A prevalence of >55% was observed in older people suffering from systemic diseases, including diabetes, Parkinson’s disease, and cancer (Anil et al 2014).
It is almost 100% in patients with Sjogren’s syndrome and those undergoing radiation therapy for head and neck cancer (Anil et al 2014). Sjogren’s syndrome is a condition that involves dry mouth and dry eyes and that may be accompanied by rheumatoid arthritis or a related connective tissue disease (Plemons et al 2014).
Sjogren’s syndrome, the most common autoimmune disease, is characterised by inflammation of the exocrine glands and can occur in association with other autoimmune diseases, such as RA, systemic sclerosis, or systemic lupus erythematosus; it is more prevalent in older adults and more common in postmenopausal women (Anil et al 2014).
Diabetes and HIV
Additionally, individuals with diabetes commonly complain of dry mouth, and moderate to severe xerostomia is reported by 30 to 40 percent of patients with human immunodeficiency virus (HIV), with increasing prevalence based on age and duration of HIV positivity (Plemons et al 2014).
Rheumatoid arthritis (RA) is a systemic disease of the connective tissue that affects approximately 1% of the world’s population and has a three times higher prevalence in women than in men (Anil et al 2014). It has been reported that RA disturbs the structure and function of salivary glands, as reflected by changes in the salivary flow and composition (Anil et al 2014). However, xerostomia in patients with RA could be due to other additional causes, such as secondary Sjogren’s syndrome and/or the use of xerogenic drugs (Hopcraft and Tan 2010).
Diagnosis of dry mouth
Salivary flow rates or sialometry provide surrogate information on salivary gland function, and are therefore important diagnostic aids in ascertaining salivary gland pathology (Anil et al 2014). Salivary flow rates can be measured in many different ways, either from each major gland or from a mixed sample of the oral fluids, termed “whole saliva” (Anil et al 2014). Biopsy and subsequent microscopic examination of labial minor salivary glands have been routinely used in the diagnosis of major gland pathology (Anil et al 2014).
Among the clinical signs and symptoms of xerostomia are (Plemons et al 2014):
- Increased incidence of tooth decay (cervical and incisal)
- Enamel demineralization (chalky spots at the cervical regions of the teeth)
- Enamel erosion and attrition
- ORAL MUCOSA
- Mucosal desquamation
- Recurrent oral candidiasis
- Dryness, fissuring, lobulation
- MAJOR SALIVARY GLANDS
- Poor salivary output
- Frothy saliva
- Absent or reduced salivary pooling
- ORAL CAVITY
- Oral allergic or contact reactions
- Difficulty talking, chewing or swallowing (dysphagia)
- Plaque accumulation
A positive response to any of the following questions has been associated with reduced saliva, even in patients who have not expressed complaints of xerostomia (Plemons et al 2014):
- Does the amount of saliva in your mouth seem to be too little?
- Does your mouth feel dry when eating a meal?
- Do you sip liquids to aid in swallowing dry food?
- Do you have difficulty swallowing?
The consequences of dry mouth such as caries may be used as a surrogate marker for the condition (Scully 2003). For example, persons taking three or more prescription medications have a higher Root Caries Index (RCI) than those taking none, one or two drugs, and people who take antidepressants and antiulcer drugs have the highest RCI values (Scully 2003).
Unstimulated whole saliva often is collected by means of the draining or drooling method, in which a patient’s head is tilted forward and pooled saliva is collected into a sterile container, and an unstimulated whole saliva flow rate of less than 0.1 milliliter per minute is suggestive of significant SGH (Plemons et al 2014). Stimulated whole saliva is collected by challenging the glands through mastication, such as chewing paraffin wax, or through gustatory stimulation using citric acid, followed by expectoration into a collection tube (Plemons et al 2014). Stimulated whole saliva flow rates below 0.7 mL/min are within the lower range of output and suggest salivary hypofunction (Plemons et al 2014).
Patients with dry mouth, dry eyes and salivary gland enlargement should be promptly evaluated for Sjögren syndrome, as these individuals have a 16-fold increased risk of lymphoma compared with the general population (Plemons et al 2014). Prompt diagnosis allows for recognition of comorbid diseases, and encourages aggressive management of ocular and intraoral complications (Plemons et al 2014).
Drugs associated with dry mouth
A review of the 200 most frequently prescribed drugs (in USA in 1992), showed the most frequent oral adverse drug reactions (ADRs) to be dry mouth (80.5%), dysgeusia (47.5%), and stomatitis (33.9%) (Smith and Burtner 1994). Generally, no specific drug or drug‐group is especially xerogenic; rather, polypharmacy is strongly correlated to reported symptoms of dry mouth, and there is a significant correlation between increasing dry mouth and the number of medications used (Nederfors 1996).
Xerostomia is prevalent in young patients taking antidepressants, with a 22 times higher risk than normal subjects, again indicating that the condition is a side-effect of various diseases and the medications used to treat these diseases, rather than a disease all its own (Anil et al 2014). However, this is not to say that disease can always be excluded as a cause of dry mouth; for example, saliva secretion is more affected by xerogenic drugs and autonomic nervous dysfunction in patients with non‐insulin‐dependent diabetes than in non‐diabetic controls (Scully 2003).
More than 500 drugs are known to cause oral dryness, including many of the most commonly prescribed classes of medications, including (Plemons et al 2014):
- Anticholinergic drugs
- Antihypertensive agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, α- and β-adrenergic blockers, diuretics
- Psychotropic agents, including antidepressants, antipsychotics
- Skeletal muscle relaxants
Over-the-counter medications often associated with xerostomia include those used to treat allergic conditions, congestion, motion sickness and diarrhea (Plemons et al 2014).
Opioids are well‐recognized causes of dry mouth (Bruera et al 1999) and atropine, hyoscine and atropinics have long been used to reduce secretions pre‐operatively. Controlled‐release morphine sulphate suppositories are associated with adverse events especially constipation, nausea, anorexia, and dry mouth (Bruera et al 1999).
Tiredness and dry mouth were also reported in 80% of patients after use of dihydrocodeine (Freye et al 2001). Tramadol, a synthetic, centrally acting analgesic agent with two distinct, synergistic mechanisms of action, has ADRs including nausea, dizziness, drowsiness, sweating, vomiting and dry mouth (Scott and Perry 2000). Dry mouth is also the only significant side‐effect of transdermal scopolamine (hyoscine) (Gordon et al 2001).
A number of appetite suppressants can cause dry mouth, including sibutramine, which inhibits the uptake of serotonin and noradrenaline, but may induce dry mouth, headache and fatigue (Bray 2001), and fenfluramine plus phentermine, which can produce dry mouth in 41% of users (Weintraub et al 1992).
Long‐term drug treatment of schizophrenia with conventional phenothiazine antipsychotics is commonly associated with ADRs including dry mouth. ADRs such as uncomfortable dry mouth, movement disorders, sleep problems and weight gain do not differ between oral and depot forms of fluphenazine enanthate (Moditen) or decanoate (Modecate) (Adams and Eisenbruch 2000). Newly developed antipsychotic drugs with more potent and selective antagonistic activity against the dopamine D(2) receptor may however, not necessarily be associated with a lower incidence of ADRs such as dry mouth (Scully 2003).
Table 1: Medications related to incidence of xerostomia (Hopcraft and Tan 2010).
Diuretics and psychotropics
Diuretic agents and psychotropics were the most commonly used xerostomatic medications in one study of elderly patients, and were almost equally potent in reducing mean salivary flow rate (Persson et al 1991). For example, xerostomia was experienced 10 times more frequently after ingestion of furosemide than placebo (Atkinson et al 1989).
With the advent of SSRIs as first‐line treatments for major depression, there is considerable debate as to whether they are as effective or as potent as first‐generation tricyclic antidepressants (TCAs) or the mixed reuptake inhibitor, venlafaxine, all of which exert considerable effect on noradrenaline reuptake (Scully 2003). While often promoted as having significantly less anticholinergic side‐effects than the TCAs, dry mouth may still be seen in patients on SSRIs, e.g. fluoxetine (Scully 2003).
Systemic retinoids are well known to cause dryness of the mouth and changes in oral and lip mucosa, as seen with the advent of etretinate and 13 cis‐retinoic acid (Scully 2003). A study to evaluate changes in salivary variables during 3 months treatment with oral isotretinoin showed a significantly lower mean flow rate of stimulated saliva during the period of medication than at baseline (Oikarinen et al 1995).
Treatment of xerostomia
The most important step in the management of patients with xerostomia is establishing the correct diagnosis – xerostomia, SGH or both (Hopcraft and Tan 2010). Next, it is important to develop an appropriate preventive programme to minimize the risk of dental caries, including regular dental visits, dietary and oral hygiene assessment and advice (Hopcraft and Tan 2010).
A multidisciplinary model of care for xerostomia and SGH should include the following components (Plemons et al 2014):
- Patient education – a patient-centered process emphasizing daily oral hygiene, regular dental visits, use of topical fluoride, tobacco-use cessation counseling and other interventions;
- Management of systemic conditions and medication use in consultation with the patient’s physician, oncologist or other health care provider;
- Preventive measures to reduce oral disease and associated complications;
- Pharmacologic treatment with salivary stimulants (sialogogues); and
- For patients who cannot tolerate sialogogues, palliative measures to improve salivary output may be considered, such as using sugar-free salivary stimulants (e.g. chewing gum).
Patients with SGH may benefit from pH neutralization strategies when buffering capacity is in question, and these strategies may include traditional methods such as stimulating saliva by using sugar-free gum or candies, as well as pharmacotherapies (Plemons et al 2014). It is also important to note that professional office treatments, home-use fluoride products, dental sealants and dietary counseling are considered the first line of defense in caries prevention (Plemons et al 2014).
Stimulation of salivary output can be achieved using pharmacological agents known as sialogogues, which are regarded as well-tolerated medications (Plemons et al 2014). Response to these medications may vary based on the amount of healthy acinar cells within the salivary glands and patients with extensive salivary gland damage, such as those with radiation-induced SGH, may not respond as well as do patients with less severe damage (Navazesh 2017).
The treatment of xerostomia appears to be very individualised, and patients often have to try different saliva substitutes to find the most suitable one for them (Partenhauser and Bernkop-Schnurch 2016).
Recently, the beneficial qualities of ectoine, a natural compound found in bacteria, have been highlighted in terms of dry mouth relief (Muller et al 2016). In a separate study, it was found that ectoine-containing lozenges improve pharyngitis-related pain such as pain on swallowing, tickle in the throat and hoarseness (Dao et al 2019). This study, performed in a real-life setting, showed that treatment with ectoine lozenges is more effective and tolerable than treatments with hyaluronic lozenges and hypertonic saline gargle in patients with moderate-to-severe symptoms of acute viral pharyngitis (Dao et al 2019). All patients treated with ectoine-containing lozenges were also highly satisfied with the taste (Dao et al 2019).