12 Journal of Public Health Dentistry
Medication and Dry Mouth: Findings from a Cohort Study of
Older People
W. Murray Thomson, BDS, MA, MComDent, PhD; Jane M. Chalmers, BDSc, MS;
A. John Spencer, BDSc, MPH, PhD; Gary D. Slade, BDSc, DDPH, PhD
Abstract
Objectives: The aim of this study was to examine the association between
medication exposure and (1) unstimulated whole-salivary flow rate and (2) the
severity of xerostomia among olderpeople while adjusting for multiple medication
use. Methods: Data were obtained from participants remaining at the five-year
follow-up phase of a cohort study of community-dwelling older South Australians.
Medication exposure information was available at baseline and at five years,
enabling examination of the effects on dry mouth of long-term exposure to
medications. At the five-year follow-up, unstimulated salivary flow was estimated
using the spit method, and xerostomia severity was estimated using the 1 l-item
Xerostomia Inventory. Because of the potential difficulties posed by polyphar-
macy, a two-stage analytical approach was employed: (1) Classification and
Regression Tree (CART) analysis was used as an exploratory device to elucidate
the relationships among the dependent and independent variables, and (2) linear
regression analysis was used as a complementaryprocedure. Results: Unstimu-
lated flow rate was lower among individuals who were female or taking antide-
pressants at both baseline and five years, and higher among smokers or people
who were taking hypolipidemic drugs. Xerostomia severity was higher among
females, or individuals taking: (1) an anginal at baseline and five years, (2) an
anginal without a concomitant betablocker at five years, (3) thyroxine and a
diuretic at five years, or (4) antidepressants or antiasthma drugs at both baseline
and at five years. Conclusions: These results suggest that polypharmacy can
be accounted for to a certain extent by using CART analysis in conjunction with
more conventional approaches; and that the relationship between medications
and dry mouth is a complex one, and differs according to which aspect of dry
mouth is being examined. [J Public Health Dent 2000;60( 1): 12-20]
Key Words: medication, xerostomia, hyposalivation, cohort study, polypharmacy.
Our present understanding of the
relationship between medications and
dry mouth in older people is incom-
plete. A recent review of the causes of
salivary gland dysfunction stressed
that, because most investigations of
the association of medications and dry
mouth have been conducted with con-
venience samples of healthy younger
people or patients who were taking
particular medication types, "the rela-
tionship of salivary function and indi-
vidual medications in the unhealthy
elderly is largely untested" (1).
Dry mouth has been reported to af-
fectbetween 10 percent and 44 percent
of older people (2-5), and the chronic
use of medications has been suggested
as an important etiological factor, with
one review listing more than 400 dif-
ferent preparations implicated in the
relationship (6). Medications most
commonly implicated in reviews of
the field and in epidemiologic studies
include antihypertensives (6,7), an-
ticholinergics (4,6,8,9), antidepres-
sants (6-8,10,11), antipsychotics (6,10),
and antihistamines (2,6,8,10). Prepara-
tions less consistently implicated in-
clude anti-Parkinsonian drugs (6,8),
diuretics (2,6,8-10,12,13), anorectics
(6), cardiac agents (including anginals)
Send correspondence and reprint requests to Dr. Thomson, Department of Oral Health, University of Otago, PO Box &47, Dunedin 9001, New
Zealand. E-mail: mthomson@gandalf.otago.ac.nz. Web site: http://www.otago.ac.nz. Ms. Chalmers and Dr. Spencer are affiliated with the
Department of Dentistry, University of Adelaide, South Australia. Dr. Slade is with the Department of Dental Ecology, University of North Carolina,
Chapel Hill. Manuscript received 10/2/98; returned to authors for revision: 11/13/98; accepted for publication: 7/8/99.
(7,11), psychotherapeutic agents
(6,8,10,11,13,14), and analgesics (15).
Without exception, current evidence is
from cross-sectional studies where
drug exposure and outcome (dry
mouth) were measured simultane-
ously. The important issue of duration
of exposure has not been addressed,
and there is an implicit assumption
that the medications implicated in
those studies had been taken for a suf-
ficiently long period to have had de-
tectable effects on mouth dryness at
the time of measurement.
There are a number of prerequisites
for satisfactory study of the relation-
ship between medications and dry
mouth. First, a suitable method must
be used for capturing and analyzing
medication data. Second, xerostomia
(the subjective perception of dry
mouth and its consequences) and sali-
vary gland hypofunction (as meas-
ured by salivary flow rate) should be
estimated separately, given the possi-
bility that they may be largely discrete
conditions (16). Third, xerostomia
should be measured as a continuous
variable, so that an estimate of symp-
tom severity can be obtained for each
individual, and the possibility of mis-
classification bias minimized. Fourth,
a longitudinal design should be used
so that duration of exposure to the
various medications can be estimated
prospectively. Finally, participants
should (ideally) comprise a repre-
sentative sample so that findings can
be generalized to the larger popula-
tion.
Polypharmacy presents a formida-
ble methodologic challenge. Most
older people take at least one medica-
tion, and the majority take more than
one. With one exception (2), not one of
the reported analyses of medications
and dry mouth has attempted to ad-

Vol. 60, No. 1, Winter 2000 13
dress the issue of multiple medication
use. There are at least two possible
reasons for this. First, it is analytically
complex, and the risk of Type I error
increases with the larger number of
statistical tests that are required when
conventional approaches are used.
Second, there are very real sample size
limitations. For example, if only the
most prevalent 20 medication types
are examined in an epidemiologic
study of older people, there are still 219
different possible combinations of
medications to examine, and the Bon-
ferroni-corrected alpha value for that
number of tests would be 0.00000005.
For there to be meaningful numbers in
each combination subgroup, the
number of individuals in the sample
would have to be prohibitively large.
Moreover, as so much is unknown
about the relationship between medi-
cation use and dry mouth, conven-
tional a priori approaches carry the
very real risk of missing a substantial
association. Analyses therefore need
to have more of an exploratory ap-
proach than is customary in
epidemiologic studies. Two other po-
tential problems are: (1) possible inter-
correlations among the predictors (for
example, someone taking an anginal is
more likely to be taking a betablocker
than someone who is not); and (2) pos-
sible interaction effects, the detection
of which may be problematic because
of the considerable a priori knowledge
required.
Aside from medications, epide-
miologic studies have suggested a
number of other modifiers of the oc-
currence of dry mouth among older
people. Sex is frequently cited, with
the most common finding being that
xerostomia is more prevalent among
females (1 0,15,17,18). The association
between sex and flow rate is less clear,
with some studies reporting lower
flow rates among older females
(2,7,10,19); however, a recent study of
a convenience sample of older people
in Rochester reported no sigruficant
association (18). Smoking also has
been implicated, but the findings to
date are equivocal. Xerostomia was re-
ported to be associated with current
smoking among males in the Roches-
ter study, but the possible association
between salivary flow rate and smok-
ing was not reported (18). No associa-
tion was found between xerostomia
and smoking among a sample of older
women who were retiring from the
work force (20); however, an increased
secretion (by 27%) from the minor sali-
vary glands among smokers was re-
ported recently (21). Although the lat-
ter finding pertained to the minor
gland secretions only (as major gland
output was not measured), it suggests
that the local irritant effect of tobacco
smoke may actually increase glandu-
lar output. Support for this effect can
be found in the recent Swedish popu-
lation-based study of dental status and
smoking (22), where male smokers
had significantly higher stimulated
salivary flow rates than male non-
smokers. Unstimulated flow rate was
not estimated in that study, and it is
notable that smokers reported more
frequent dry mouth. On the basis of
the evidence from these studies, to-
bacco usage should be considered to
be at least a potential modifier of the
occurrence of dry mouth in older peo-
ple, if only on the basis of the wide-
spread observations of smoking's det-
rimental associations with many other
biological and health characteristics.
Similarly, alcohol use also should be
considered a potential modifier: while
no epidemiologic association has re-
ported on alcohol use and dry mouth,
a report of increased flow rates in labo-
ratory rats chronically exposed to
ethanol (23) raises the possibility that
a similar phenomenon might be ob-
served among humans. It is appropri-
ate, therefore, to include smoking and
alcohol exposure as explanatory vari-
ables when modeling the occurrence
of dry mouth.
There are no reports from longitudi-
nal studies of the association between
dry mouth and particular medications
in community-dwelling older people,
and none have made allowances for
polypharmacy. The purpose of the
present study was to examine the as-
sociation between dry mouth and five-
year exposure to medications that
commonly are taken by noninstitu-
tionalized older people, while allow-
ing for multiple medication use.
Methods
The south Australian Dental Longi-
tudinal Study (SADLS) began in 1991,
and is a cohort study of older people
living in Adelaide and Mt. Gambier,
South Australia. The SADLS sampling
strategy and data collection have been
described previously (24), with the
baseline and two-year data collections
taking place in 1991 and 1993, respec-
tively. Dry mouth was not investi-
gated at baseline or two years. At five
years (1996), the participants again
were examined and interviewed, with
computer-assisted telephone inter-
views being conducted just prior to the
clinical examination.
At the five-year follow-up, the
Xerostomia Inventory (25) was sent to
all examination participants as one of
two postal questionnaires, and partici-
pants were instructed to bring the
completed questionnaires to the clini-
cal examination or return them by
post. The Xerostomia Inventory (or
"XI") is an 11-item summed rating
scale that requires respondents to
choose one of five responses (never=l,
hardly ever=2, occasionally=3, fairly
often=4, and very often=5) to the fol-
lowing statements: "my mouth feels
dry," "my lips feel dry," "I get up at
night to drink," "my mouth feels dry
when eating a meal," "I sip liquids to
aid in swallowing food," "I suck
sweets or cough lollies to relieve dry
mouth," "my throat feels dry," "the
skin of my face feels dry," "my eyes
feel dry," "my lips feel dry," and "the
inside of my nose feels dry." Each in-
dividual's responses are scored and
summed to give a single XI score that
has a theoretical range from 11 to 55.
Initial testing of its content and con-
struct validity has been reported pre-
viously (25).
Unstimulated whole saliva was col-
lected at the five-year clinical exami-
nation appointment using the "spit"
method (26). Each participant had
been instructed to refrain from eating,
drinking, and smoking for the 60 min-
utes prior to collection. Some five min-
utes before collection, participants
were instructed to rinse out the mouth
with plain water and then to sit quietly
while administrative procedures were
attended to. Immediately prior to sa-
liva collection, each participant was
asked to clean the mouth by swallow-
ing, and then to actively spit saliva into
a preweighed plastic collection tube
over the next four minutes. At the end
of that time, a beeper sounded and the
participant was asked to spit any re-
maining saliva into the tube, which
was then sealed and placed in a cool
storage bin. The collection time was
recorded. The tubes were weighed
later at the University of Adelaide. Un-
stimulated saliva flow (in ml/min)
was computed as the weight of saliva
collected (assuming 1 g=1 ml) divided