Paper 036 MS

Palliative care

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.

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

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-
European Journal of Cancer Care, 1997, 6, 209±214
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.

# 1997 Blackwell Science Ltd.

Ahed Dhed Table marker

Bhed Ref marker Ref end
Ched Fig marker Ref start
DAVIES Xerostomia
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
210 # 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214
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.
# 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214
European Journal of Cancer Care
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
211
DAVIES Xerostomia
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.
212 # 1997 Blackwell Science Ltd, European Journal of Cancer Care, 6, 209±214
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

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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