VOL22.NO. 3, 1996
Problems and Progress in
the Diagnosis and
Treatment of Polydipsia
and Hyponatremia
by Cherlan Verghese,
Jos6 de Leon, and
Richard C. Josiassen
Abstract
Fluid-electrolyte balance is regulated within a narrow range and disturbances in this system are unusual
in animals and humans. Studies
from the preneuroleptic era to date
suggest that up to 25 percent of
patients with schizophrenia have
polydipsia, suggesting that it is
related to the pathophysiology of
the psychoses. Polydipsia and the
related phenomenon of hyponatremia cause considerable mortality
and morbidity. Prevalence studies
are limited by imprecise measures
available at present The treatment
was limiting water intake when
patients reached critical levels of
water retention, which however did
not improve polydipsia. Recent case
reports and open studies have
shown that clozapine improves both
polydipsia and water retention. The
response occurs at low doses and is
not related to improvement in psychosis. This may not be applicable
to all patients and better understanding of the pathophysiology of
polydipsia-hyponatremia would
lead to more empirically derived
treatments.
Schizophrenia Bulletin, 22(3):
455-464,1996.
One of the primary needs of any
human being is maintenance of a
constant fluid level in the body. All
living tissue depends directly on
water, and the regulation of fluid
intake and outflow is an elegantly
precise process. Water is continuously excreted and secreted by the
body in the processes of waste
removal, breathing, and temperature
regulation; and the intact organism
manages to maintain its water balance within surprisingly narrow limits. The early work of Adolph (1943)
demonstrated that water balance is
maintained at approximately ± 0.22
percent of body weight. When water
loss exceeds 0.5 percent of total body
weight, an individual becomes
thirsty and seeks water. Under normal conditions, fluid regulation is so
precise that humans stop drinking
when sufficient fluid is consumed to
correct the state of dehydration, even
though actual fluid balance in tissue
occurs hours after drinking (Ramsay
and Thrasher 1990). When an individual overdrinks, various regulatory
mechanisms immediately begin to
operate, and a sense of bloating, nausea, and dizziness is induced. Thus,
with the exception of certain medical
conditions (e.g., diabetes), excessive
fluid intake (polydipsia), excessive
fluid excretion (polyuria), and retention of excessive fluid leading to low
serum sodium levels (hyponatremia)
are rarely seen in humans (Anderson
et al. 1985; Vokes et al. 1988). In this
light, estimates that polydipsia may
be present in up to 20 percent of
chronic psychotic inpatients (Koczapski et al. 1990) suggest a highly
unusual phenomenon worthy of scientific scrutiny.
Historical Considerations
Among schizophrenia researchers,
awareness of polydipsia, polyuria,
and hyponatremia dates back to the
early part of this century (Rowntree
1923; Hoskins 1933; Pfister 1934;
Sleeper 1935; Miller 1936). In a chapter entitled "Psychosomatic Aspects
of Schizophrenia," Hoskins (1946)
noted that urine output among schizophrenia patients was "nearly twice
that of control subjects living in the
Reprint requests should be sent to Dr.
C. Verghese, The Medical College of
Pennsylvania, 3200 Henry Ave.,
Philadelphia, PA 19129.
SCHIZOPHRENIA BULLETIN
456
same environment and eating the
same food" (p. 155). He went on to
speculate that the finding "suggested
a defect in the diencephalic-pituitary
controlling mechanisms" (p. 155).
Sleeper (1935) followed this descriptive account with the first empirical
study of polyuria in which 92 male
schizophrenia patients were catheterized, and 25 percent were found to be
polyuric (> 3 L/day).
Sleeper and Jellinek (1936) then
turned to various biochemical measurements and directly compared the
most severe cases of polyuria (upper
quartile) with the least severe cases
(lower quartile). They found no biochemical differences between the
groups and no evidence of impaired
renal excretory capacity. They concluded that "the explanation of the
polyuria seems to reside more in the
psychical than in the physiological or
biochemical domain" (p. 563). They
went on to note that upon water
restriction, the polyuria ceased without complication, suggesting that an
"excessive urge to drink" played the
primary role in the disorder and that
polyuria itself was only a secondary
consequence of the excessive consumption. There also were early case
reports of water intoxication (Barahal
1938) as well as the important observation that some patients were
unable to excrete excess fluid, which
could result in low serum sodium
levels (Pfister 1934) and even death
(Rowntree 1923).
By modern standards these early
studies were limited in methodology,
and most contemporary researchers
would disagree with the suggestion
of a psychogenic etiology. Nevertheless, these original reports from a
pre-pharmacological era make it
clear that polydipsia and certain
interrelated phenomena were seen in
a significant fraction of chronic psychotic patients and that this distur-
bance of water regulation was dearly
not a side effect of medication.
Prevalence of Polydipsia and
Hyponatremia
After Hoskins (1933) and Sleeper
(1935) published their reports of
polydipsia and polyuria, several
decades passed before other
researchers began to again discuss
fluid dysregularion among chronic
patients (Barlow and De Wardener
1959; Langgard and Smith 1962).
With this renewed interest came the
convention that polydipsia was
defined as the consumption of 3 or
more liters of fluid per day and in
extreme cases up to 10 or more liters
per day. Any mental health professional or layperson could identify the
cases of grossly excessive fluid intake
and the extreme consequences, but
the precise and valid quantification
of polydipsia itself remained elusive.
Diagnosing Polydipsia. The obvious method for diagnosing polydipsia is measurement of daily fluid
intake. This ideal index, however, has
seemed impossible to achieve within
the psychiatric context. It requires
considerable staff resources and a
highly cooperative patient. Unfortunately, clinical settings are not usually equipped with sufficient staff or
facilities to undertake this level of
monitoring. Moreover, many chronic
psychiatric patients will not cooperate with intrusive monitoring of fluid
intake or are secretive regarding their
drinking behavior.
As a result in the psychiatric literature there are no prevalence studies
of polydipsia based on direct measurement of fluid intake. Instead,
patient samples identified on the
basis of extreme forms of the disorder have been studied. Patients with
milder grades of polydipsia or poly-
dipsia with mild hyponatremia are
not easily differentiated from the
general inpatient population.
Although it has been suggested that
even mild grades of polydipsia with
hyponatremia can impair cognition,
this decline often goes unnoticed
since there are no accompanying perturbations in affective symptoms or
psychosis (Gehi et al. 1981). Thus,
very little is known about milder
grades of polydipsia with or without
hyponatremia.
Diagnosing Polyuria. In the absence of precise measures of polydipsia and linked with the knowledge
that fluid balance in humans is maintained within very narrow limits,
many investigators have turned to
polyuria to infer the presence of
polydipsia. In a general sense, urine
excretion is highly correlated with
fluid intake, and therefore daily urine
volume offers a reasonable approximation of fluid consumption. Urine
collection for a period of 24 hours is
an ideal way to diagnose polyuria
and infer polydipsia, but again this
simple, direct approach has seldom
been used among psychiatric patients
(Sleeper 1935; Lawson et al. 1985).
Instead, methods to estimate urine
volume have been developed. Evidence suggests that afternoon urine
creatinine concentrations and specific
gravity are both highly correlated
with 24-hour urine volume (Goldman et al. 1992). Estimates of polydipsia are based on measures of daily
weight gain or on chart evidence for
patients with severe clinical symptoms. A recent review of the literature
by de Leon et al. (1994) reports that
with these various approaches, the
estimates of polydipsia range from 3
percent (using chart review) to 39
percent (using specific gravity of
urine). Our own cross-sectional surveys based on two independent State
VOL 22, NO. 3, 1996
hospital samples suggest at least a 20
percent prevalence rate. In the first
survey (de Leon et ah, in press), 93 of
360 chronic inpatients were judged to
have primary polydipsia without
known medical causes, based on staff
report and on specific gravity of
urine. In a second, more comprehensive survey of 633 inpatients at Norristown State Hospital, Nematbakhsh
et ah (1996) used staff report, specific
gravity of urine, and diurnal weight
gain to assess prevalence rates. Although this second series is still
being analyzed, at least a 20 percent
prevalence rate of primary polydipsia probably represents a reasonable
estimate and is in line with the original Sleeper (1935) finding.
These derived estimates of polyuria have served a useful purpose in
acquiring data on polydipsia. Unfortunately, each of the methods is vulnerable to specific sources of artifact
and, therefore, provide only a partial
solution to the problem of measuring
polydipsia. The widespread use of
pharmacological agents is a crucial
source of artifact. For example,
lithium antagonizes antidiuretic hormone at the level of the renal tubule,
which would increase free-water
clearance and result in greater urine
output. Any diuretic would also
influence urine volume. Another
problem occurs when polydipsic
patients have water retention rather
than polyuria, which would actually
concentrate the urine in the presence
of polydipsia and invalidate estimates of urine volume. In a small
sample of 27 patients, we have
shown that a subgroup of patients
have significant diurnal weight gain,
putting them at risk for hyponarrerrtia, without showing low urine
specific gravity (Verghese et ah 1995).
Similar findings were seen in a hospital-wide survey of 230 patients
(Verghese et ah, in preparation).
457
Clearly, before large-scale studies of
polydipsia can be meaningfully
undertaken, better diagnostic tools
that use direct measures of water
intake and retention are needed.
Emergence of Hyponatremia.
Within the older psychiatric literature, polydipsia and polyuria were
usually described as benign conditions. It was thought that, even
though patients may consume excessive fluid, the outflow of fluid
through excretion, breathing, and
temperature regulation kept up with
the excessive intake. The unusual
cases where fluid intake exceeded
fluid output, leading to dilutional
hyponatremia, were considered
"idiopathic polydipsia." Recent literature, however, suggests that a significant fraction of polydipsic
patients cannot handle the excessive
levels of fluid consumption and
begin to retain water. This retention
may be secondary to effects of neuroleptics or to more careful scrutiny.
This situation results in chronic or
recurrent episodes of hyponatremia
and hypoosmolarity associated with
symptoms of water intoxication. The
actual prevalence of hyponatremia
among patients with polydipsia and
polyuria is unknown, but estimates
are that from 25 to 86 percent of polydipsic patients go on to develop
hyponatremia with symptoms of
water intoxication (de Leon et ah
1994). Unfortunately, polydipsia with
hyponatremia is often missed, or
chronic patients with seizures secondary to hyponatremia are erroneously diagnosed with idiopathic
epilepsy and are treated with anticonvulsant medication (Erhardt and
Goldman 1991).
Diagnosing Hyponatremia. Although the prevalence of hyponatremia secondary to polydipsia is
unknown, the diagnosis of hyponatremia itself is easily made using
well-established laboratory tests.
Hyponatremia develops when excessive fluid consumption leads to a
rapid fall of serum sodium. An acute
drop in serum sodium level of 10
mEq/L over a few hours may produce recognizable clinical symptoms
(Koczapski and Millson 1989), including restlessness, diarrhea, salivation, nausea, ataxia, stupor, and
coma. Of particular concern is evidence that episodes of hyponatremia
are associated with high mortality
among patients. For example, Vieweg
et ah (1985) reported that in one State
hospital 18 percent of deaths among
schizophrenia patients under the age
of 53 years were associated with
hyponatremia. In our own experience, however, even markedly diminished sodium levels (i.e., 10 mEq/L
below normal) may produce no obvious symptoms if the serum sodium
drop occurs over days or weeks.
Because patients may be normonarremic between episodes, the diagnosis may require not only laboratory
tests, but also a careful history focusing on latent symptoms of water
intoxication (Goldman 1991).
An indirect way of establishing the
risk for hyponatremia is through
measuring diurnal weight changes
(Godleski et ah 1989). Vieweg et ah
(1989) showed that under normal
conditions normal body weight in
healthy individuals did not increase
by more than 1.2 percent in 1 day,
whereas patients with chronic schizophrenia showed more than a 4 percent daily weight gain on average.
With this fall in serum sodium,
symptoms may increase over time, or
patients may be asymptomatic and
then suddenly convulse.
Over many years the chronic and
severe polydipsic patient may go on
to develop frank physical complica-
458
tions, such as bowel and bladder
hypotonicity, hydronephrosis, renal
failure, and congestive heart failure
(Blum et al. 1983; Zubenko et al.
1984).
In summary, the prevalence of
polydipsia is unclear. It appears to be
a frequently underdiagnosed condition among patients with chronic
schizophrenia, and, based on indirect
measures, it may be present in at
least 20 percent of chronic patients. A
significant proportion of patients
with polydipsia go on to develop
dilutional hyponatremia and the
associated clinical symptoms of
water intoxication, which in extreme
cases can be fatal. Over long periods
of excessive fluid consumption, additional physical conditions may
emerge to further complicate the clinical picture.
Approaches to Treatment
Inasmuch as polydipsia and hyponatremia are a frequent source of morbidity and mortality in patients with
chronic schizophrenia, it is remarkable how little sound information has
been acquired about the treatment of
these conditions. The few reported
treatment studies take two forms:
behavioral management, focused on
reducing fluid intake, and pharmacological interventions, focused on altering central nervous system (CNS)
mechanisms of fluid regulation.
Behavioral Management Although
polydipsia itself may not be sufficient
to produce marked hyponatremia
(Goldman et al. 1988), excess fluid
intake and its retention is a necessary
condition for dilutional hyponatremia. Several researchers have
shown that behavioral management
of fluid intake is an important focus
of intervention. Vieweg et al. (1989)
SCHIZOPHRENIA BULLETIN
demonstrated that a 4 percent increase in daily weight due to water
retention is associated with an acute
drop of 10 mEq/L of serum sodium.
Delva and Crammer (1988) found
that the percentage increase in
weight from morning to evening
(termed normalized diurnal weight
gain) correlated (r = 0.99) with the
drop in sodium. Therefore, managing
daily water intake among polydipsic
patients is an important preventive
intervention.
Voluntary water restriction rarely
succeeds with psychiatric patients.
Therefore, Delva and Crammer
(1988) suggested that regular monitoring of normalized diurnal weight
gain will identify patients consuming
excess fluids. Goldman and Luchins
(1987) described a similar technique
(termed target weight procedure)
that individualizes the amount of
weight a patient could safely gain. To
date, these are the most widely used
behavioral techniques for managing
polydipsic patients. Patients are
weighed at least twice daily (more
often if necessary), and involuntary
water restriction is imposed when
the patient exceeds a certain normalized diurnal weight gain (5% in one
report by Godleski et al. 1989).
Unfortunately, this target weight procedure is not uniformly effective in
detecting risk for hyponatremia
because of individual differences
among patients. It also consumes
considerable staff time and is restrictive to the patient.
In one explicitly behavioral study,
Baldwin et al. (1992) used a tokeneconomy method to reinforce
reduced fluid consumption with five
patients suffering from both polydipsia and hyponatremia. They used
urine specific gravity and normalized
diurnal weight gain over a 1-year
period to assess behavioral improvement and found a stabilizing effect.
The long-term maintenance of treatment effects is unclear, as no followup data were reported. Another
study of time-limited group psychotherapy reported behavioral
improvement in fluid consumption
that rapidly declined when the group
concluded (Millson and Glackman
1993). Both studies were conducted
in highly structured inpatient settings, and how much they can be
generalized to less intensive settings
is unclear.
In summary, if a marked increase
in weight from morning to evening is
observed in a polydipsic patient, it is
most likely due to excessive fluid
consumption. The regular monitoring of this acute change in body
weight can be imposed and involuntary fluid restriction put in place to
reduce precipitous hyponatremia.
Pharmacological Interventions in
Polydipsia. Although involuntary
fluid restriction is effective in highly
structured inpatient settings, it is
probably not feasible within less formal clinical settings. More important,
the restriction of fluid intake appears
to have little or no influence on the
excessive urge to drink. As a result,
several investigators have turned to
pharmacological interventions to
treat either the polydipsia itself or the
hyponatremia.
One pharmacological approach
used antihypertensive propranolol in
the treatment of polydipsia. The
rationale for using this p-adrenergic
receptor antagonist is based on two
complementary lines of work; isoproterenol (an adrenergic agonist) is a
known dipsogen that can reliably
induce drinking (Fitzsimons and
Setler 1975); laboratory animals
treated with p-adrenergic receptor
antagonists show a decrease in drinking. This latter effect may be mediated through central mechanisms
VOL22.NO. 3, 1996
that may decrease peripheral production of angiotensin II (All), a wellknown dipsogen. Based on this logic,
two case studies have reported the
use of propranolol, and both describe
improvement in polydipsic symptoms. Goldstein and Folsom (1991)
used 80-120 mg/day of propranolol
and found a reduction in the use of
seclusion for water intoxication, their
only outcome measure. Kathol et al.
(1986) also reported the use of propranolol. These two reports, which
have not stimulated any larger studies, are only suggestive.
A second pharmacological approach to the treatment of polydipsia
has used angiotensin-convertingenzyme (ACE) inhibitors. It is well
known that ACE inhibitors antagonize peripheral All and that among
laboratory animals All is one of the
most potent and reliable stimuli for
fluid intake (Fitzsimons and Setler
1975). A small number of case studies
have reported varying degrees of
success using ACE inhibitors to treat
polydipsia. Goldstein (1986) reported
that the ACE inhibitor captopril, at a
dose of 12.5 mg/day, immediately
stopped polydipsia and polyuria in a
77-year-old woman who drank approximately 10 L/day. Lawson et al.
(1988) reported improvement in
polydipsia (measured by staff report,
urine specific gravity, and volume)
and water retention (measured by
random serum sodium) in another
single case study. Captopril 6.25 mg
t.i.d. was used in addition to neuroleptics. Lawson et al. (1988) then
conducted an open trial of six patients at the same dose of captopril,
which did not show convincing evidence of improvement in either polydipsia or hyponatremia. In another
case report of ACE inhibitor treatment, Sebastian and Bernardin (1990)
state that enalapril "dampened
weight fluctuations" and improved
459
sodium levels; unfortunately, the outcome measures were not dearly specified. Although interesting, the case
reports of the nine patients in this
study are inconclusive.
A third pharmacological strategy
has used opioid antagonists following the observation that opioid
antagonists are effective in treating
water drinking in genetically polydipsic mice (Ukai and Holtzman
1988). In a series of studies with very
small samples (n of 1, 3, and 6
patients), Nishikawa and colleagues
found that the opioid antagonist
naloxone improved the symptoms of
polydipsia (Nishikawa et al. 1992,
1994<i, 1994b). They measured normalized diurnal weight gain
(NDWG) at a pretrearment baseline,
during naloxone treatment, and during naloxone withdrawal. They
found that treatment with naloxone
reduced NDWG and that the patients
returned to baseline NDWG levels
when naloxone was withdrawn.
Although interesting, the Nishikawa
samples were very small, and it is not
clear whether the improvement was
in polydipsia itself or was related to
water retention.
A fourth pharmacological approach is based on the chance observation that dozapine may be effective in the treatment of polydipsia
and hyponatremia. As shown in table
1, over 40 patients have shown improvement in either polydipsia or
hyponatremia or both with dozapine
treatment. Most of the studies are of
single cases or very small samples,
and in most studies the range of outcome measures was limited. However, the recent report from Spears et
al. (19%) substantiates the previous
case reports that dozapine treatment
may significantly improve the key
clinical parameters of sodium and
water deregulation in patients with
polydipsia and hyponatremia. They
followed 11 patients with documented polydipsia for 26 weeks
before dozapine treatment and then
for 26 weeks of dozapine treatment.
Across the group they found a corrective and stabilizing effect of dozapine on measures of sodium metabolism, on thirst regulation, and on
measures of water metabolism.
Among the other studies, there are
interesting hints for further investigation. For example, in our prospective
study of two cases (Verghese et al.,
submitted for publication), both
hyponatremia and hypoosmolality
improved within the first 4 weeks of
treatment, while the polydipsia itself
took up to 12 weeks to improve.
Another intriguing observation is
that dose of dozapine may not be an
important factor. Many of the
patients reported on in the literature
have been put on high doses of dozapine because they were being treated
primarily for psydiosis. However,
one patient in our study showed
reduced polydipsia and hyponatremia on a daily dose of 100 mg with
10 and 16 ng/mL serum levels of
dozapine (well below the suggested
level of 350 ng/mL for psychosis). It
also appears that improvement in
polydipsia and hyponatremia is not
secondary to improvement in the
psychosis, since some patients did
show improvement of polydipsia
and hyponatremia without changes
in psychosis.
Some additional clinical observations should be noted. In our ward
experience, there have been patients
whose symptoms of polydipsia and
hyponatremia did not respond to
dozapine. We have also seen patients
with polydipsia or hyponatremia
whose response to dozapine was
only partial (although clinically
important), while in other patients
with a very good treatment response,
breakthrough episodes of hypona-
1
4
6
1
5
4
8
4
11
2
Leeetal. (1991)
Munn (1993)
Spears etal. (1993)
Gupta and Baker (1994)
Henderson and Goff
(1994)
Lysteretal. (1994)
Canuso and Goldman
(1995)
de Leon etal. (1995)
Spears etal. (1996)
Verghese et al.
(submitted for
publication)
Pros
Pros
(1) Retrcr
(3) Pros
Pros
Retrcr
Retrcr
Urvol
Spgu
Urosm
Urosm
Urvol
Spgu
SR
SR
Urvol
Urvol
SR
NR/NA
SR
Urvol
Retrcr
Pros
SR
SR
Spgu
PD
Retr cr
Pros
Design
6-300
5,6,700
NR/NA
4
4
4
4
NR/NA
4-500
±800*
4
4
4
Na (a.m./p.m.) 4
Serosm
(a.m./p.m.)
NDWG
100,300
3,6,900
4
4
4
NR/NA
4
4
NR/NA
550
CLZ dose
(mg)
WR
NR/NA 4
4
4
4
4
PD
4
NDWG
Serosm
(a.m./p.m.)
Na (a.m./p.m.)
Restr
Seiz
NDWG, Na
Serosm
Seiz
Restr Na
Na
(? a.m./p.m.)
Na
(? a.m./p.m.)
Na (p.m.)
Na
(? a.m./p.m.)
NDWG
WR
Change^
WR: 4 wks
PD: 12 wks
2 wks
8 wks
1-6 wks
NR/NA
NR/NA
NR/NA
NR/NA
NR/NA
NR/NA
4-6 wks
Time to
response
BPRS t
BPRS t
4
4
No change
NR/NA
3 patients
no change
1 patient not
reported
4
4
NR/NA
4
BPRS 4
Effect on 1
psychosis
2
4* o decrease, t = Increase.
± Indicates the quantity is equivocal.
1
Note.—BPRS - Brief Psychiatric Rating Scale (Overall and Gortiam 1962) ; Na = serum sodium levels; f•JDWG = normalized diurnal weight gain; NR/NA = not reported or not
available; PO = poiydipsia; Pros •» prospective study; Restr = use of restraints; Retr cr = retrospective chart review;!Seiz = seizure; Serosm o serum osmolallty, Spgu = specific
gravity of urine; SR o staff report;; Urosm c• urine osmotality; Urvol = unne volume; WR • water retention
n
Study
Measures
Table 1. Overview of studies using clozapine (CLZ) in the treatment of poiydipsia and hyponatremia
CD
-o
m
I
o
CO
o
VOL.22, NO. 3, 1996
tremia and polydipsia were observed. It is also important to note
that Ogilvie and Croy (1992) reported
one case in which dozapine appeared to induce hyponatremia. They
also noted that The Sandoz Clozapine Monitoring Service in the
United Kingdom knew of two other
cases of hyponatremic seizures with
dozapine.
It was inevitable that the effects of
dozapine on polydipsia would be
evaluated, since severe polydipsia
and hyponatremia are most often
noted in chronic and treatment-resistant patients who are also candidates
for clozapine treatment. Clearly,
these studies were done on selected
groups of severely ill patients, and it
is not at all dear whether clozapine
would be effective or indicated in all
patients with polydipsia or hyponatremia or both. Moreover, clozapine
has well-known side effects, including orthostatic hypotension, lowering
of seizure threshold, anticholingeric
toxicity, and significant inddence of
agranulocytosis (l%-2%). Many
patients with polydipsia or hyponatremia may have multiple physical
illnesses that could preclude the use
of dozapine. Obviously, systematic
studies of larger samples of patients
are needed to clarify the efficacy of
the treatment, predictors of improvement, aspects of polydipsia that
improve, and time course of
improvement.
Pharmacological Intervention in
Hyponatremia. Pharmacological
treatments of hyponatremia have
been limited in number, and useful
findings have not yet emerged.
Demedocydine, a tetracydine derivative, has been reported to improve
hyponatremia in two cases (Nixon et
al. 1982; Khamnei 1984). However, a
double-blind, placebo-controlled
study with demedocydine found no
461
significant effect on serum sodium
(Alexander et al. 1991). Vieweg et al.
(1988) report the use of lithium with
or without phenytoin to block antidiuretic hormone (ADH), which would
have the effect of increasing freewater clearance. Lithium antagonizes
ADH at the level of the renal tubule,
which is the basis of lithium-induced
polyuria. Perhaps this treatment approach has not been widely studied
because lithium could exacerbate
polydipsia by increasing urine
volume.
In the case of acute hyponatremia,
administration of sodium tablets has
been suggested (Godleski et al. 1989).
If the patient is water intoxicated,
water restriction per se would be
helpful, as subsequent diuresis
would result in improvement of
sodium levels. However, the rapid
correction of hyponatremia can result
in debilitating or fatal central pontine
myelinolysis (Tanneau et al. 1994).
Guidelines for managing hyponatremia have been reviewed by
Vieweg and Karp (1994).
In summary, polydipsia and
hyponatremia are a frequent source
of morbidity and mortality, yet very
little sound information has been
acquired about the treatment of these
conditions. The few treatment studies
using clozapine have found a corrective and stabilizing effect on polydipsia and hyponatremia.
Conclusion
Over half a century has passed since
Rowntree (1923), Hoskins (1933),
Pfister (1934), Sleeper (1935), and others began to discuss fluid dysregulation among chronic patients. An
observational and speculative literature has accumulated about the relation between schizophrenia and fluid
dysregulation, yet prospective, wellcontrolled investigations remain to
be performed. There is fairly general
agreement that polydipsia is a frequently underdiagnosed condition
that may be present in at least 20 percent of chronic schizophrenia patients. A significant proportion of
patients with polydipsia go on to
develop dilutional hyponatremia and
the assodated clinical symptoms of
water intoxication, which in extreme
cases can be fatal. Over long periods
of excessive fluid consumption, additional physical conditions may
emerge to further complicate the clinical picture. The finding that dozapine may have a corrective and stabilizing effect on polydipsia and
hyponatremia provides an important
hint regarding disturbances of fluid
consumption and sodium metabolism. Even though measures reflecting these disturbances do not correlate (Goldman et al. 1988) and may
have different neurobiologkal substrates, the dozapine findings suggest that we are gradually approaching a time when fruitful experimental
efforts can be undertaken.
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The Authors
Cherian Verghese, M.D., is Research
Assistant Professor of Psychiatry,
Medical College of Pennsylvania and
Hahnemann University, Philadelphia, PA. Jos£ de Leon, M.D., is Research Assistant Professor, Medical
College of Pennsylvania, and Medical Director, Clinical Research Center. Norristown State Hospital, Norristown, PA. Richard C. Josiassen,
Ph.D., is Associate Professor of Psychiatry, Medical College of Pennsylvania/Eastern Pennsylvania Psychiatric Institute and Hahnemann University, Philadelphia, PA.