The management of xerostomia: a review

ANDREW N. DAVIES, MB BS MRCP, Registrar in Palliative Medicine, St Christopher's Hospice, 51±59 Lawrie

Park Road, Sydenham, London SE26 6DZ, UK

DAVIES A.N. (1997) European Journal of Cancer Care 6, 209±214

The management of xerostomia: a review

Xerostomia causes a great deal of morbidity in patients with advanced cancer. However, it is an area which

has received little attention. Indeed current management of xerostomia in palliative care units is based

largely on anecdotal evidence. There are a number of studies in progress specifically looking at patients

with advanced cancer, but until these are published we should take note of studies done in other patient

groups. This article reviews the medical literature on the symptomatic management of xerostomia as a

whole, with particular reference to treatments that are currently available in the United Kingdom.

Keywords: xerostomia, review literature, palliative treatment.

Palliative care

INTRODUCTION

Xerostomia is the subjective sensation of dryness of the

mouth. It is usually, but not invariably, associated with

hyposalivation (Sreebny & Valdini, 1988). However, in

some patients the composition of the saliva may be altered

(Wiseman & Faulds, 1995). Saliva has a number of

functions, and hyposalivation may result in oral discom-

fort, and problems with taste, mastication, deglutition and

speech. It may also predispose to dental caries and other

oral infections such as Candida albicans.

The prevalence of xerostomia has been variously

reported as 30% in a mixed group of patients receiving

palliative care (Ventafridda et al., 1990), and 77% in a

group of patients admitted to a hospice (Jobbins et al.,

1992). However, it is thought that the incidence, i.e. the

percentage of patients who have xerostomia at some time

during their illness, is even greater (Twycross & Lack,

1986). Furthermore, it seems that dry mouth is a very

distressing symptom in up to 30% of patients dying from

cancer (Addington-Hall & McCarthy, 1995).

In patients with advanced cancer, xerostomia may be: (a)

caused by the cancer itself, e.g. destruction of the salivary

glands; (b) related to the cancer or debility, e.g. dehydra-

tion; (c) related to cancer treatment, e.g. drug treatment,

radiotherapy, (d) caused by a concurrent disorder, e.g.

Sjogren's syndrome; or (e) due to a combination of the

above (Twycross & Lack, 1986). Although in some patients

it is possible to treat the underlying cause and any

contributing factors, in the majority of patients it is not.

The aim of this article is to review the medical literature

on the symptomatic management of xerostomia, with

particular reference to treatments that are currently

available in the United Kingdom. (Treatments that have

not been formally assessed have not been included in

the article).

MANAGEMENT

The symptomatic management of xerostomia involves the

use of both saliva substitutes and saliva stimulants.

Individual patients may also benefit from referral to a

dietician or a dentist (Walls & Murray, 1993).

Saliva substitutes

Saliva is a complex substance, which has a number of

functions. Saliva substitutes fall into a number of cate-

gories, depending on the specific function they are trying

to replicate. Only those saliva substitutes which are used

specifically to treat xerostomia will be discussed here.European Journal of Cancer Care, 1997, 6, 209±214

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210 # 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214

Water

Patients with xerostomia commonly use water as a saliva

substitute. In a double-blind study, the effectiveness of

water was compared with that of artificial saliva in

patients with xerostomia of varying aetiology (Olsson &

Axell, 1991). The patients were given 15 ml of the

solutions to rinse their mouth with, and both subjective

and objective, i.e. mucosal friction measurements, effects

recorded. The mean duration of subjective improvement

with water was 12 minutes, whilst the mean duration of

objective improvement was 5.5 minutes. These values are

about half the values seen with artificial saliva.

Artificial saliva

The most commonly prescribed saliva substitutes are the

artificial salivas. These are complex substances, usually

based on either mucin or carboxymethylcellulose (Levine

et al., 1987). Mucin is a normal constituent of saliva, and

the mucin-based artificial salvas appear to be more

effective and better tolerated than the carboxymethylcel-

lulose-based ones ('S-Gravenmade et al., 1974; Vissink et

al., 1983; Visch et al., 1986). However, even the mucin-

based artificial salivas are not particularly good saliva

substitutes (Levine et al., 1987).

In the Olsson study (Olsson & Axell, 1991), the mean

duration of subjective improvement in xerostomia with a

mucin-based artificial saliva was 18 minutes, whilst the

mean duration of objective improvement in mucosal

friction was 11.5 minutes. This short duration of action

has been confirmed by other investigators (Vissink et al.,

1983). Furthermore, the mucin-based artificial salivas tend

to have a longer duration of action than the carboxy-

methylcellulose-based ones (Vissink et al., 1983).

In another double-blind study, the same mucin-based

artificial saliva was compared to flavoured water, and its

non-mucin base, and found to be overall more effective

(Duxbury et al., 1989). However, the water was ranked as

the best treatment more often than the mucin-based

artificial saliva, and only 47% of the patients wanted to

continue with it after the study period. Again, the mucin-

based artificial salivas tend to be persevered with more

than the carboxymethylcellulose-based ones (Vissink et

al., 1983; Visch et al., 1986).

The artificial salivas are available in a variety of forms

including sprays and lozenges, and have been incorporated

into swab sticks (Poland et al., 1987) and reservoirs in den-

tures (Vissink et al., 1984; Toljanic & Schweiger, 1985).

The mucin is derived from porcine gastric mucosae, and

therefore this product is not suitable for Jews, Muslims

and certain other groups. Carboxymethylcellulose-based

artificial salivas are associated with sticky accumulations

in the mouth, which may result in irritation of the

underlying mucosa ('S-Gravenmade et al., 1974; Vissink et

al., 1983). This appears to be less of a problem with mucin-

based ones. The artificial salivas are not usually associated

with systemic side-effects.

Glycerine

Glycerine, often used in combination with lemon, has

been recommended as a saliva substitute (Greenspan,

1990). However, it can itself cause a dry mouth (Van

Drimmelen & Rollins, 1969; Poland et al., 1987). Further-

more, in comparative studies glycerine has been found to

be subjectively less effective than artificial saliva (Klestov

et al., 1981; Poland et al., 1987).

Saliva stimulants

Secretion of saliva is under the control of the autonomic,

primarily the parasympathetic, nervous system. A number

of stimuli can cause an increase in salivary flow, including

stimulation of taste, touch, pressure and proprioceptive

receptors within, and around, the oral cavity. Saliva stimu-

lants fall into two categories: those that stimulate the

aforementioned receptors (afferent pathways), e.g. organic

acids and chewing gum, and those that act directly on the

parasympathetic nerves (efferent pathways), e.g. pilocarpine.

Ascorbic acid (vitamin C)

Ascorbic acid tablets are often used to treat xerostomia in

palliative care units (Twycross & Lack, 1986), although

there is little evidence to support their use. In a study from

Sweden, the effectiveness of ascorbic aid was compared

with that of artificial saliva and a number of other saliva

stimulants in patients with xerostomia of varying aetiol-

ogy (Bjornstrom et al., 1990). Ascorbic acids was found to

be subjectively more effective than artificial saliva, but

less effective than the other saliva stimulants. Indeed, only

23% of the patients wanted to continue with the tablets at

the end of the study. Furthermore, a number of the

patients developed local irritation when using them.

Ascorbic acid is also known to cause demineralization of

the teeth (Anneroth et al., 1980), and so is not suitable for

long-term use in dentate patients.

Citric acid

Citric acid, often in the form of hard-boiled sweets, is

again often used to treat xerostomia (Twycross & Lack,

1986). In an uncontrolled study, a mouthwash containing

1% citric acid was found to be effective in patients with

non-radiation-induced xerostomia (Spielman et al., 1981).

However, patients with radiation-induced xerostomia did

not respond to the mouthwash. Interestingly, subjective

improvement in the sensation of dryness of the mouth was

associated with an objective increase in salivary flow in

only 55% of cases. The mouthwash was generally well

tolerated, although three out of 34 patients had to

discontinue using it because of a burning sensation. Citric

acid, like ascorbic acid, can have a detrimental effect on

the teeth (Newbrun, 1981).

Malic acid

Malic acid is a naturally occurring acid found in apples,

pears and certain other fruits. In the Bjornstrom study

(Bjornstrom et al., 1990), 44% of the patients wanted to

continue with the pastilles at the end of the study, and

local irritation was not a significant problem. However,

malic acid is again known to cause demineralization of the

teeth (Anneroth et al., 1980), and so is again not suitable

for long-term use in dentate patients.

Sweets

Sweets containing citric and malic acid are often used to

treat xerostomia (Twycross & Lack, 1986). In an uncon-

trolled study, mints were found to increase salivary flow in

patients with xerostomia (Abelson et al., 1989). However,

subjective improvement in the sensation of dryness of the

mouth, duration of the effect, and acceptability of the

treatment, were not recorded.

Chewing gum

There have been a number of studies that have shown that

chewing gum increases salivary flow in patients with

xerostomia of varying aetiology (Markovic et al., 1988;

Abelson et al., 1990; Olsson et al., 1991; Aagaard et al.,

1992; Risheim & Arneberg, 1993), although the duration of

the effect was not recorded. This objective improvement

in salivary flow was associated with subjective improve-

ment in xerostomia, and when asked 56±79% of patients

wanted to continue using the chewing gum at the end of

the study (Olsson et al., 1991; Aagaard et al., 1992). Indeed

in the Bjornstrom study (Bjornstrom et al., 1990), chewing

gum was the most preferred treatment.

Chewing gum has not been used much in palliative care

units, partly because of concerns about its acceptability.

However, this does not seem to be an issue, even in older

patients (Aagaard et al., 1992). Chewing gum is generally

not associated with side effects (Aagaard et al., 1992;

Risheim & Arneberg, 1993), although it may cause local

irritation (Olsson et al., 1991).

Chewing gum appears to increase salivary flow, mainly

as a result of stimulation of taste receptors, although

stimulation of other receptors, as a result of the act of

mastication, also occurs (Abelson et al., 1989).

Nicotinamide

Nicotinamide is one of the vitamin B group. It was also

one of the treatments in the Bjornstrom study (Bjornstrom

et al., 1990), and 35% of the patients wanted to continue

with the tablets at the end of the study. The tablets were

not given to patients with radiation-induced xero-

stomia because of the theoretical risk of stimulating tu-

mour growth.

Pilocarpine

There have been a number of controlled studies that have

shown that pilocarpine is an effective treatment for

radiation-induced xerostomia (Greenspan & Daniels,

1987; Schuller et al., 1989; Fox et al., 1991; Le Veque et

al., 1993; Johnson et al., 1993; Rieke et al., 1995), and

xerostomia due to disease of the salivary glands, e.g.

Sjogren's syndrome and chronic non-specific sialadenitis

(Fox et al., 1986, 1991). It has also been used successfully

in drug-induced xerostomia (Chambers et al., 1996; Salah

& Cameron, 1996).

The response to pilocarpine appears to depend to a

certain extent on the aetiology of the xerostomia. Thus,

whilst most patients with xerostomia due to salivary gland

disease or drugs found it helpful (Fox et al., 1986;

Chambers et al., 1996), only 51±54% of patients with

radiation-induced xerostomia did (Johnson et al., 1993;

Rieke et al., 1995). Furthermore, subjective improvement

in the sensation of dryness of the mouth was not

necessarily associated with an objective increase in

salivary flow (Johnson et al., 1993; Le Veque et al.,

1993). In most patients the response to pilocarpine is

immediate (Fox et al., 1991). However, in patients with

radiation-induced xerostomia it may take up to 12 weeks

for a response to be seen (Johnson et al., 1993; Le Veque et

al., 1993). Saliva production is greatest 1 hour after a dose,

and the increase in salivary flow lasts for about 4 hours

(Fox et al., 1991).

In a crossover study from the UK, a mouthwash

containing pilocarpine was compared to artificial saliva

# 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214 211

European Journal of Cancer Care

in patients with radiation-induced xerostomia (Davies &

Singer, 1994). The patients generally found the pilocarpine

more effective, and 47% wanted to continue with it after

the study period. Only 18% of the patients wanted to

continue with the artificial saliva.

Pilocarpine is primarily a muscarinic agonist, although

it does have some effect on the beta-adrenergic receptors

within the salivary glands (Ferguson, 1993). The side-

effects seen are mainly the result of generalized para-

sympathetic stimulation, e.g. sweating, headache, urinary

frequency, vasodilatation (Johnson et al., 1993; Rieke et

al., 1995), and their incidence is dose related. Sweating is

the commonest side-effect, occurring in 29±37% of

patients taking 5 mg three times a day (Johnson et al.,

1993; Rieke et al., 1995). It is also the commonest reason

for discontinuing the drug (Johnson et al., 1993). With the

doses used clinically there are no significant effects on the

cardiovascular system.

Other parasympathomimetics

Other parasympathomimetic drugs, including the choline

esters bethanechol (Everett, 1975; Epstein et al., 1994) and

carbachol (Joensuu et al., 1993), and the anticholinesterases

distigmine (Wolpert et al., 1980) and pyridostigmine

(Teichman et al., 1987), have been used to a much lesser

extent in the management of xerostomia.

Acupuncture

Although acupuncture has long been recognized as a

treatment for xerostomia in Chinese medicine (Hansen,

1975), it is only relatively recently that it has been adopted

by Western medicine. In a controlled study from Sweden,

acupuncture was found to be effective in patients with

xerostomia of varying aetiology (Blom et al., 1992). The

active group received traditional Chinese acupuncture

utilizing local, distant and auricular points, whilst the

control group received `placebo acupuncture', i.e. super-

ficial needling, 1±2 cm from these points. Each group

received a 6-week course of twice weekly treatments,

which was repeated after a gap of 7±10 days. Interestingly,

increases in salivary flow were seen in both groups,

although they were more pronounced and longer lasting

in the active group. Indeed, the increase in salivary flow

continued for at least a year in the active group, whilst it

only lasted for the period of the study in the placebo group.

Subjective improvement in xerostomia was not recorded.

The acupuncture was associated with other positive

effects, e.g. patients `felt better', and there were few side-

effects, i.e. haematomas, tiredness after treatment.

The mechanism by which acupuncture increases sali-

vary flow has not yet been worked out. However, it is

known that it causes an increase in blood flow within the

mouth (Blom et al., 1990), and there also appears to be a

significant placebo effect (Blom et al., 1992).

Dietary advice

Patients with xerostomia can often be greatly helped by

simple dietary advice, including the types of food to try,

the types of food to avoid, and increasing fluid intake

whilst eating.

CONCLUSION

Xerostomia causes a great deal of morbidity in patients

with advanced cancer. However, as can be seen from this

article, it is an area which has received little attention.

Indeed, current management of xerostomia in palliative

care units is based largely on anecdotal evidence (Twy-

cross & Lack, 1986; Regnard & Fitton, 1995). There are a

number of studies in progress specifically looking at

patients with advanced cancer, but until these are

published we should take note of studies done in other

patient groups.

In the studies that have compared saliva substitutes with

saliva stimulants, patients have preferred the saliva stimu-

lants (Bjornstrom et al., 1990; Davies & Singer, 1994).

Furthermore, there is some evidence that saliva stimulants

can `switch on' the salivary glands, i.e. the increase in

saliva flow continues after the saliva stimulant is discon-

tinued (Spielman et al., 1981; Aagaard et al., 1992; Blom et

al., 1992). Therefore, patients should be routinely managed

with saliva stimulants, rather than saliva substitutes. The

choice of saliva stimulant will depend on a number of

factors, including the aetiology of xerostomia, the patient's

general condition and prognosis, the presence or absence of

teeth and, most importantly, the patient's preference.

Chewing gum is effective and well tolerated, and may be

a good first line treatment (Bjornstrom et al., 1990).

Patients with xerostomia often receive a number of

other treatments (e.g. antifungals, antiseptics, local an-

algesics) as part of a general mouthcare package. However,

these products will become redundant if there is an

increase in salivary flow. Furthermore, some of them,

e.g. chlorhexidine gluconate and benzydamine hydrochlor-

ide, may themselves cause xerostomia (Sonis et al., 1985).

Thus, patients with xerostomia should be assessed

regularly and their treatment altered accordingly.

As mentioned at the beginning of this article, only

treatments that are currently available in the United

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212 # 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214

Kingdom have been reviewed. However, there are a

number of other treatments available elsewhere in the

world, or still under development, which also show

promise in this condition.

Acknowledgements

I would like to thank Denise Brady and the other members

of staff in the library at St Christopher's Hospice for

obtaining the often obscure references for this article.

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