Xerostomia (Dry Mouth)

Xerostomia is the subjective sensation of oral dryness.^{1, 2} Dry mouth is a common, complex and under-recognized condition, which may or may not be associated with salivary gland hypofunction (i.e., the objective measurement of reduced salivary flow).^3-5

Saliva is a complex mixture of fluids that provides several protective functions, including cleansing the oral cavity, facilitating speech and swallowing, protecting oral tissues (including teeth) against physical and microbial insults, and maintaining a neutral pH.⁶ Reduced salivary flow can cause difficulties in tasting, chewing, swallowing, and speaking; it can also increase the chance of developing dental caries, demineralization of teeth, tooth sensitivity, and/or mucosal infections.^{4, 7}

There are a variety of potential causes of xerostomia, including dehydration, medication use, toxicity of chemotherapy and/or radiation therapy of the head and neck, autoimmune diseases, other chronic diseases, and nerve damage.⁸ Patients can be variably affected.⁸

Severity of dry mouth symptoms ranges from mild oral discomfort to significant oral disease that can compromise the patient’s health, dietary intake, and quality of life.¹ Estimates of xerostomia prevalence in the general population vary widely depending on case definitions used and differences in study samples (e.g., age range, health status).⁹  Previous studies reported xerostomia prevalence estimates ranging from 10 to 26% in men to 10 to 33% in women.¹⁰ A 2018 systematic review reported an overall estimated prevalence of xerostomia in approximately 22% of the global population.¹¹  Xerostomia prevalence is generally higher among older individuals, typically due to polypharmacy and with the onset of various medical conditions over time. Virtually all patients with Sjögren disease or radiation therapy for head and neck cancer develop dry mouth.¹²

Saliva is a mixture of secretions from the major (i.e., parotid, submandibular, sublingual) and minor salivary glands located in the oral mucosa.¹³ In healthy individuals, the daily production of saliva normally ranges from 0.5 to 1.5 liters.¹⁴ Saliva is 99% water and less than 1% solids, including a number of electrolytes (e.g., sodium, potassium, calcium, bicarbonate, phosphate) and organic components (e.g., immunoglobulins, proteins, enzymes, mucins).^{13, 15} In addition to keeping tissues moist and helping to digest food, saliva cleanses the oral cavity, makes it possible to chew and swallow food, facilitates oral sugar clearance and serves as a buffer that protects oral mucosa against orally ingested acids or regurgitated stomach acid. ^{1, 7, 16} Salivary proteins and mucins contribute to the lubrication and coating of oral tissues, protecting the mucosa from chemical, microbial, and physical injury (e.g., abrasion).^{1, 7} Without adequate salivary flow, tooth decay and a variety of oral infections can develop.^{7, 13} Xerostomia symptoms may also worsen at night because salivary output reaches its lowest circadian levels during sleep, and the problem can be exacerbated by mouth breathing.¹⁷

Reduced salivary flow can interfere with chewing or swallowing certain foods which may result in malnutrition.⁷ Significant loss of salivary gland function is associated with altered taste sensation (i.e., dysgeusia)^{1, 14} and difficulty in swallowing (i.e., dysphagia).^{18, 19} 

Drug/Therapy-Related

Medication-Induced Xerostomia.  The most frequent cause of hyposalivation is use of certain medications.⁴ A 2018 systematic review concluded that urologic medications, antidepressants and psycholeptics were associated with dry mouth in older adults.²⁰ Another systematic review (completed in conjunction with the World Workshop of Oral Medicine VI) reported that 106 medications had strong to moderate evidence of being associated with salivary gland dysfunction, including anti-depressants (e.g., fluoxetine) and anti-muscarinic medications (e.g., tolterodine for overactive bladder).² An additional 46 medications in the same systematic review² were found to have weak evidence of interfering with salivary gland function.

Over-the-counter (OTC) and prescription medications that can contribute to or exacerbate oral dryness include: antihistamines (for allergy or asthma), antihypertensive medications, decongestants, pain medications, diuretics, muscle relaxants, and antidepressants.^{8, 13, 21, 22} The most common types of medications causing salivary dysfunction have anticholinergic effects, e.g., tricyclic antidepressants, antihistamines, antihypertensive medications, and antiseizure/antispasmodic drugs.²³ Patients who are taking multiple medications may be at a higher risk of dry mouth as an adverse effect of therapy.¹⁴ Overall, the likelihood of decreased salivary flow rates tends to increase in the presence of numerous diseases and medications; however, individuals may still report and experience the subject sensation of xerostomia while having salivary flow rates that fall within a normal range (i.e., without an observable decrease in salivary flow).¹⁶ Dry mouth is also commonly reported as a minor adverse effect of medical cannabis use, along with drowsiness, dizziness and nausea.²⁴

Drug substitutions may help reduce the dry mouth effects of certain medications (e.g., selective serotonin-reuptake inhibitor antidepressants tend to cause less dry mouth than tricyclic antidepressants).^{17, 23, 25} Dry mouth symptoms from medications may also be reduced if patients who are taking anticholinergic medications can take them during the day, rather than at night (avoiding nocturnal symptoms), and in divided doses, rather than one larger, single dose (potentially avoiding the xerostomic adverse effects).^{17, 23}

Toxicity Related to Cancer Chemotherapy or Head and Neck Cancer Radiotherapy.  Oral complications of cancer chemotherapy or head and neck cancer radiotherapy^{13, 23, 26} can be acute (i.e., develop during therapy) or chronic (i.e., develop months to years after therapy).²⁶ These therapies can cause xerostomia/salivary gland hypofunction via direct toxicity to salivary glands and oral tissues, or indirect damage due to regional or systemic toxicity.^{23, 26} Generally, cancer chemotherapy causes acute toxicities that resolve following discontinuation of therapy and healing of damaged tissue, whereas radiation therapy can cause acute oral toxicity, as well as induce permanent tissue damage that can put patients at lifelong risk.^{23, 26}

Xerostomia can also occur following hematopoietic stem-cell transplantation and as part of salivary gland graft versus host disease.²⁶ Sialadenitis, or infection of the salivary gland, is another potential acute oral toxicity associated with chemo/radiotherapy.²⁶  Radioactive iodine, which is used to treat some thyroid cancers, can damage salivary glands (primarily the parotid glands) in a dose-dependent fashion.^{17, 23}

Physiological or Disease-Related

Aging. Xerostomia affects an estimated 30% of patients older than 65 years and up to 40% of patients older than 80 years; this is primarily an adverse effect of medication(s), although it can also result from comorbid conditions such as diabetes, Alzheimer’s disease, or Parkinson’s disease.^27-29 Xerostomia, while common among older patients, has been found to be twice as likely to occur in adult patients who take one of more drugs daily when compared with medication-free individuals.³⁰ Xerostomia prevalence is also higher among individuals with an intake of more than four daily prescription medications.²⁹

Autoimmune Disease.  Sjögren disease (formerly known as Sjögren syndrome) is the second most common autoimmune connective-tissue disease,³¹ and is the systemic condition most frequently associated with salivary dysfunction and xerostomia.¹⁷  Approximately 90 percent of those with Sjögren disease are women, and patients often experience associated symptoms such as fatigue and joint pain.³² Although Sjögren disease is a systemic condition that can affect multiple body organs or systems,³³ the primary symptoms are dry mouth and dry eyes.^{7, 13, 31} Sjögren disease causes chronic inflammation and dysfunction, and may also result in persistent or recurrent salivary gland swelling.^{29, 34, 35}

Primary Sjögren disease (i.e., Sjögren disease alone) affects approximately 1 in 70 people; this number approximately doubles if patients with other major autoimmune or rheumatic disease (e.g., rheumatoid arthritis) in addition to Sjögren disease are included³¹ (i.e., secondary Sjögren disease¹⁷). Other autoimmune diseases that can occur with Sjögren disease include systemic lupus erythematosus, scleroderma, polymyositis, and polyarteritis nodosa.¹⁷

Other Conditions.  Other conditions associated with dry mouth include:^{1, 7, 8, 13, 21, 36-38}

Burning mouth syndrome
COVID-19
Cystic fibrosis
Graft-versus-host disease
Hepatitis C virus infection
HIV infection/AIDS
Hormonal changes (e.g., pregnancy or menopause)
Lymphoma
Nerve damage from a head or neck injury
Poorly controlled diabetes
Psychogenic causes
Salivary gland agenesis or aplasia
Stroke
Uncontrolled hypertension

Potential lifestyle causes of xerostomia include the use of alcohol and tobacco or cannabis use, or the consumption of excessive caffeine or spicy food.^{6, 39}

• a sticky, dry, or burning feeling in the mouth
• trouble chewing, swallowing, tasting, or speaking
• altered taste or intolerance for spicy, salty, or sour foods or drinks
• a dry or sore throat
• cracked, peeling, atrophic or sticky lips
• a dry, rough tongue
• mouth sores
• oral fungal infection (e.g., candidiasis)
• hoarseness
• halitosis (bad breath)
• inability to retain dentures or otherwise poorly fitting removable prostheses

The goals of treating xerostomia include identifying the possible cause(s), relieving discomfort, and preventing complications, e.g., dental caries and periodontal infections.⁶

Identification

Patients with complaints of dry mouth should undergo a detailed medical and dental history to help with early detection and identification of potential underlying causes.^{1, 17, 29} In patients with xerostomia or salivary gland hypofunction, oral examination may reveal dry and friable oral mucosa and the tongue may appear dry and fissured.^{1, 22} Patients may commonly have dental caries (especially root, cervical, or incisal/cuspal tips), plaque accumulation, gingivitis, and/or periodontitis.^{1, 22, 40} Infections (e.g., oral candidiasis) and enlargement of salivary glands from sialadenitis may also be present.^{1, 17, 22, 40} Other oral manifestations evident on examination may include angular cheilitis, mucositis, traumatic oral lesions, dry lips or dry throat, and/or difficulty in wearing/retaining oral prostheses.^{17, 22, 40-42}

A thorough extraoral and intraoral examination to identify the presence or absence of salivary pooling on the floor of the mouth can help a dentist identify who will benefit from further diagnostic evaluations, such as salivary flow rate measurement, minor salivary gland biopsy, or blood and microbial tests.^{1, 4} Inspection and palpation of major salivary glands may also assist in identifying poor salivary pooling or the presence of masses, swelling or tenderness.^{1, 43} A patient is considered to have reduced salivary flow (hyposalivation) if the unstimulated salivary flow is 0.1 mL/min or less (measured for 5 to 15 minutes) or if the chewing-stimulated salivary flow is 0.7 mL/min or less (measured for 5 minutes).^{22, 40}

General Palliative/Preventive Interventions

Management of xerostomia and hyposalivation should emphasize patient education, adequate hydration and lifestyle modifications.^{1, 4} Various palliative and preventive measures, including pharmacologic treatment with salivary stimulants, topical fluoride, saliva substitutes, and use of sugar-free gum/mints, may alleviate some symptoms of dry mouth and may improve a patient’s quality of life.^{1, 22}

Examples of coping strategies for relieving dry mouth include:^{17, 21}

• sipping water or sugarless, caffeine-free drinks
• sucking on ice chips
• using lip lubricants frequently (e.g., every two hours)
• chewing sugar-free gum or sucking on sugar-free candy¹⁷
• avoiding salty or spicy food or dry, hard-to-chew foods¹⁷
• avoiding sticky, sugary foods
• avoiding irritants such as alcohol (including alcohol-containing mouthrinses²⁰), tobacco, and caffeine
• drinking fluids while eating carefully^{13, 17}
• using a humidifier at night¹⁷

Dental and oral health-specific recommendations from the National Institute for Dental and Craniofacial Research⁷ and others^{17, 22, 23} include the following for patients with dry mouth:

• brush teeth gently at least twice a day with fluoridated toothpaste
• floss teeth every day
• schedule dental visits at least twice a year (with yearly bitewing radiographs)
• use of a prescription-strength fluoride gel (0.4% stannous fluoride, 1.1% sodium fluoride) daily to help prevent dental decay
• prompt treatment of oral fungal or bacterial infections
• application of 0.5% fluoride varnish to teeth 
• dental soft- and hard-tissue relines of poorly fitting prostheses and use of denture adhesives

Salivary Stimulants.  Salivary stimulants should be considered in patients with residual salivary gland function.^{4, 17}  Sugar-free chewing gum, candies, and mints can be used to stimulate salivary output.¹⁷ The FDA has approved two oral sialologues--pilocarpine (Salagen^®, Eisai and generics)⁴⁴ and cevimeline hydrochloride (Evoxac^® capsules, Daiichi-Sankyo and generics)⁴⁵--to treat dry mouth.^{4, 23} Pilocarpine is typically administered at a dose of 5 mg three times a day for at least three months, and cevimeline is prescribed at a dose of 30 mg three times a day for at least three months.⁴ Adverse effects include sweating, cutaneous vasodilation, nausea and vomiting, diarrhea, hiccup, hypotension and bradycardia, increased urinary frequency, bronchoconstriction, and vision problems.⁴

Artificial Saliva/Saliva Substitutes/Oral Moisturizers. Artificial saliva products and oral moisturizers are available with or without prescription.  They typically contain a combination of carboxymethylcellulose and glycerin to increase viscosity, as well as buffering and flavoring agents (e.g., sorbitol, xylitol), and calcium and phosphate ions.^{8, 46}  Some products also contain fluoride.⁸ A prescription-only product, NeutraSal^® (OraPharma, Inc.), is a supersaturated calcium phosphate rinse available as powder for reconstitution.⁴⁷

The ADA Seal of Acceptance category for products for temporary relief of dry mouth means that the product is safe and has shown efficacy in temporarily relieving dry mouth symptoms, when used as directed.

Saliva substitutes are used as often as needed and although they do not cure dry mouth, they can provide temporary relief of symptoms.⁸ Alcohol-free mouthrinses, lozenges, and moisturizing oral sprays and gels are marketed as OTC oral care options for patients with dry mouth.^{8, 13, 17} There are also toothpastes specifically formulated for use in patients with dry mouth.^{8, 13}

A 2011 Cochrane review^{48, 49} found “no strong evidence” that any specific topical therapy (e.g., sprays, lozenges, mouth rinses, gels, oils, chewing gum, or toothpastes) was effective for relieving the symptoms of dry mouth. Although chewing gum was shown to increase saliva production, there was no strong evidence that dry mouth symptoms were improved. The authors noted that “patient preference is an important consideration, together with consideration of the potential adverse effects.” The review concluded that, “Well designed, adequately powered randomized controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care.”⁴⁹

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2. Wolff A, Joshi RK, Ekström J, et al. A guide to medications inducing salivary gland dysfunction, xerostomia, and subjective sialorrhea: a systematic review sponsored by the World Workshop on Oral Medicine VI. Drugs R D 2017;17(1):1-28.
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5. Wiriyakijja P, Niklander S, Santos-Silva AR, et al. World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for xerostomia. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2023 Mar 6.
6. Lynge Pedersen AM, Belstrøm D. The role of natural salivary defences in maintaining a healthy oral microbiota. Journal of Dentistry 2019;80:S3-S12.
7. National Institute of Dental and Craniofacial Research. Dry Mouth (NIH Publication No. 14-3174). National Institutes of Health. http://www.nidcr.nih.gov/oralhealth/Topics/DryMouth/DryMouth.htm. Accessed April 20, 2023.
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13. Cohen-Brown G, Ship JA. Diagnosis and treatment of salivary gland disorders. Quintessence Int 2004;35(2):108-23.
14. Mese H, Matsuo R. Salivary secretion, taste and hyposalivation. J Oral Rehabil 2007;34(10):711-23.
15. Miranda-Rius J, Brunet-Llobet L, Lahor-Soler E, Farre M. Salivary secretory disorders, inducing drugs, and clinical management. Int J Med Sci 2015;12(10):811-24.
16. Dawes C, Pedersen AM, Villa A, et al. The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI. Arch Oral Biol 2015;60(6):863-74.
17. Turner MD, Ship JA. Dry mouth and its effects on the oral health of elderly people. J Am Dent Assoc 2007;138 Suppl:15S-20S.
18. Eyigor S. Dysphagia in rheumatological disorders. World Journal of Rheumatology 2013;3(3):45-50.
19. Parisis D, Chivasso C, Perret J, Soyfoo MS, Delporte C. Current state of knowledge on primary Sjögren's Syndrome, an autoimmune exocrinopathy. Journal of Clinical Medicine 2020;9(7):2299.
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ADA Council on Scientific Affairs Report: Managing xerostomia and salivary gland hypofunction

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