PSYCHIATRIC CONSULTANT Series Editor Judith A.

NeugroschI, MD

Chronic kidney disease

Psychosocial impact of chronic pain

Sara N. Davison, MD, MHSc, FRCP(C)

Chronic kidney disease (CKD) affects more than 19 miilion peopie in The role of pain in elderly dialysis
the United States, and prevalance of CKD is expected to doubie within patients' perception of their health-re-
10 years. Additlonaliy, a significant number of predominantiy elderly lated quality of life (HRQL) appears
patients have end stage renal disease, necessitating dialysis or kidney to be greatly underappreciated. In fact,
transplant. Perception of chronic pain, especially in elderly dialysis the number and severity of physical
patients, may be greatly underrecognized. As a result, management of and mental symptoms (eg, pain, nau-
pain, as weil as depression and other physical and mental symptoms, sea, anorexia, shortness of breath, in-
may not be adequately addressed in the primary care setting. Ciinicai somnia, anxiety, depression) reported
interventions, such as psychiatric evaluation, pain management, and by elderly dialysis patients is similar
therapy to improve physical and mental symptoms, may markedly to that reported by patients hospital-
impact well-being for CKD patients. Constant reassessment is criticai ized in palliative care settings with can-
when treating CKD patients. Such an approach may significantiy better cer.^ The literature suggests approxi-
elderly patients health-related quality of life. mately 50% of dialysis patients over
Davison SN. Chronic kidney disease. Psychosociai impact of chronic pain. Geriatrics 2007; age 55 experience chronic pain and that
62(Feb):17-23. pain management is suboptimal, with
Key words: chronic kidney disease dialysis • health-related quality of 82% of these patients rating pain as
iife • depression moderate to severe.'*'^ Even in the last
Drugs discussed: amitryptyllne • buproplon • citalopram • cyciosporine day of life, pain is present in 42% of pa-
fluoxetine • Imlpramlne • litiiium • noripenephrlne • paroxetine tients withdrawing from dialysis.^
sertrallne • tacrollmus • venlafaxine
The burden of pain and other phys-
ical and mental symptoms, as previ-
ously mentioned, can account for more
than one-third of the impairment ob-
served in mental HRQL in dialysis pa-

C hronic kidney disease (CKD) is

a major public health concern
affecting more than 19 million people
started dialysis in the United States:
the majority (60%) were over age 60,
and the proportion of patients age >75
tients.^'^ Worsening of symptom bur-
den explains 46% of the deterioration
in patients' mental HRQL.^ The lack
in the United States.' More than had increased from 7.6% in 1980 to of significant association between var-
453,000 patients, predominantly eld- more than 25%, representing the ious clinical parameters, such as dial-
erly, have end stage renal disease fastest-growing group of new dialysis ysis adequacy, calcium and phospho-
(ESRD) requiring dialysis or kidney patients.^ Given the aging population rous balance, or hemoglobin and
transplantation.^ Of the 336,000 pa- and increasing incidence of diabetes HRQL, reinforces the relative impor-
tients on dialysis, 63% are age >60 and and hypertension, the prevalence of tance from a patient perspective of
approximately 14% are age >80. In CKD is projected to nearly double in symptom burden on patients' percep-
2004, more than 102,000 patients the next decade. tion of HRQL. Pain, depression, and
other physical and mental symptoms
are not adequately recognized, diag-
Dr. Davison is assistant professor of nnedicine, division of nephrology and
immunology, University of Aiberta, Edmonton, Aiberta, Canada. nosed and treated in CKD.'*'^ Clinical in-
Disclosure: The author has no reai or apparent confiict of interest with the subject
terventions (eg, pain management, psy-
under discussion. chiatric evaluation, therapy for improv-

www.geri.com February 2007 Volume 62, Number 2 Geriatrics 17

PSYCHIATRIC CONSULTANT
Table 1 Causes o( pain in dialysis patients
Etiology*
Osteoarthritis + osteoporosis
Inflammatory arthritis
Renal osteodystrophy
Peripheral polyneuropathy
Carpal tunnel
Peripheral vascular disease
Discitis/osteomyelitis^
Related to dialysis procedure
Not yet diagnosed
Other (trauma, PCKD, malignancy, calciphylaxis)
* Many patients have nnore than 1 cause for their pain.
Adapted for Geriatrics based on information from reference 4,
ing subjective assessment of physical
and mental symptoms) would have a
significant impact on well-being for
CKD patients, and are critical compo-
nents of comprehensive care for this
patient population.
Chronic pain in CKD
The causes of pain in CKD have not
been well studied but have been de-
scribed in a recent study (table I)."* Pain
may be due to concurrent comorbid-
ity; while dialysis sustains life, under-
lying systemic diseases and painful
syndromes (eg, ischemic limbs, neu-
ropathies) persists. Pain may also be
due to CKD itself as there are numer-
ous painful syndromes unique to CKD
(eg, calcific uremic arteriolopathy, re-
nal osteodystrophy). Pain may result
from the primary renal disease itself
(eg, polycystic kidney disease) or from
the dialysis procedure. Painful chronic
infections (eg, osteomyelitis, discitis)
are complications from central lines
used for dialysis access, and arteriove-
nous fistulas can lead to painful is-
chemic neuropathies.'*
Pain is a multidimensional phenom-
enon with physical, psychological and
social components. It is widely recog-
nized that chronic pain is associated
18 Geriatrics February 2007 Volume 62, Number 2
Percentage
31%
7%
5%
13%
2%
9%
2%
14%
18%
18%
with depressive disorders, psycholog-
ical distress, impairment of interper-
sonal relationships, excessive use of
health care, significant activity limita-
tions in work, family and social life,
and adoption of a chronic sick role.
Several recent reviews have reported
that the prevalence of major depression
in pain clinics often exceeds 20%.'" In
the general population, depressive
symptoms are positively associated with
pain severity, and patients with chronic
pain and concurrent depression are
likely to experience the highest levels
of pain-related impairment and psy-
chosocial disability.'""
Recent research in CKD suggests
that elderly dialysis patients' percep-
tions of physical symptoms, especially
pain, are associated with depression,
anxiety, insomnia, and greater diffi-
culty coping with stressful situations.'^
In fact, physical and mental symptom
burden appear more important than ob-
jective assessments, including assess-
ments of dialysis adequacy, bone min-
eral metabolism, and anemia, in deter-
mining CKD patients' HRQL. Al-
though loss of satisfaction with life,
sense of burden on others, and a loss of
control are the most common reasons
for considering withdrawal from dial-
ysis, regardless whether patients expe-
rience pain, patients are almost three
times more likely to consider with-
drawal from dialysis if they suffer from
chronic pain.'^
Depression in CKD
Although no large-scale, well-de-
signed, epidemiologic studies of de-
pression in patients with CKD have
been conducted, depression appears to
be a common and often underdiag-
nosed problem with a prevalence of
5% to 50% in dialysis patients.'^"'" The
wide variation in prevalence of depres-
sion has been ascribed to the different
methods and criteria for the diagnosis
of depression. Differences among eth-
nic groups may also play a role in the
variation. Most studies of depression in
CKD have looked at elderly dialysis
patients (average age: 60-65). Self-re-
ported depression as well as Beck De-
pression Inventory (BDI) scores are
associated with decreased HRQL as
well as increased risks of mortality and
hospitalization for dialysis patients. '^''^
Depression in CKD is likely multi-
factorial although is typically attrib-
uted to feelings of loss and depend-
ence.'^ Although depression can oc-
cur at any time during the course of
CKD, there are times of increased like-
lihood of a depressive episode, such as
the time leading up to and the first year
following initiation of dialysis, partic-
ularly if kidney transplantation is not
an option due to advanced age and/or
comorbidity. During this period, pa-
tients are required to make decisions
regarding treatment modality and to
make multiple and radical lifestyle
changes, all of which impact their oc-
cupation, familial role, relationships,
and leisure activities. They are expected
to assimilate information that is for-
eign and frightening.
Patients often feel unprepared for
the decisions they must make and ex-
perience feelings of helplessness and
deep personal loss, which can easily
develop into a severe depressive
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PSYCHIATRIC CONSULTANT

Table 2 The essentials of pain assessment and management

• The essentials of pain assessment include:
1. Believe the patient's report of pain.
2. Assess pain in its site, character, severity, reiieving and aggravating factors, and temporal relationships.
3. Use a simple assessment tool, such as the ESAS, which utilizes a numerical scale of 0 to 10.
A. Educate patients or their caregivers on pain assessment and charting at home.

^ Patients may have more than one kind of pain; a pain management strategy must address each syndrome.

*• Aim to achieve control at a level acceptable to the patient. It may not be necessary or possible to make the
patient completely pain-free.

>• The pain threshold may be aggravated by associated psychosocial symptoms.The psychological state of the
patient must be assessed and treated with equal concern and is best managed by an interdisciplinary team.
1. Psychological factors typically have a stronger influence on outcome than do biomedical factors.
2. Better management of psychological reactions at early stages of treatment has the potential for reducing distress
and preventing unnecessary chronicity.
3. Spiritual counseling may be useful in that spirituality may help the patient think beyond self and cope with pain
better.

>• Have knowledge of opioids and adjuvants to opioids.The five essentials of opioid (analgesic) dosing are:
1. "By mouth": whenever possible, drugs should be given orally.
2. "By the clock": schedule doses over 24 hours on a regular basis. Additional "breakthrough" medication should be
available on an "as needed" basis.
3. "By the ladder": use pain medicines "stepwise" according to the World Health Organization analgesic ladder.
4. "For the individual": there is no standard dose of strong opioids. The "right" dose is the dose that relieves pain
without causing unacceptable side effects.
5. Attention to detail: pain changes over time, thus there is the need for constant assessment and reassessment.
• Refer for non-pharmacological interventions (such as transcutaneous nerve stimulation, hot and cold
therapy, exercise, and neuromuscular massage) where appropriate.

• Educate patients and their caregivers on the goals of therapy, management plan, and potential complications.
This wiil help minimize non-compliance.

Source: Created for Geriatrics by SN Davison, MD.

episode.'* Other particularly stressful
times include the period leading to the
failure of a transplanted kidney, and
non-selection after having completed
the work-up for a kidney transplant.'*
Pain and depression in CKD
Despite the aforementioned reasons for
depression, the role of chronic pain in
depression in the elderly patient popu-
lation has been greatly underappreci-
ated. In a recent study, elderly dialysis
patients with moderate or severe chronic
pain were 2.3 times more likely to suf-
fer from depression than elderly dialy-
sis patients with no or mild chronic
pain.'^ The prevalence of depression as
defined by a BDI score of ^19 was 34%
in patients with moderate to severe pain,
compared with 18% in patients with no
or mild pain (jxO.OY). The prevalence of
insomnia was also significantly higher
in patients with moderate or severe pain
(74%), compared with patients with mild
or no pain (53%, /7<0.01, OR 2.3). Po-
tential confounders for depression (eg,
time on dialysis, gender, insomnia, co-
morbidity), were not predictive of de-
pression.'^ The results are also consis-
tent with the general population in which
chronic pain and depression frequently
coexist. In the National Health and Nu-
trition Epidemiologic Follow-up Study,
depressive symptoms were found to be
the variable most closely linked to
chronic musculoskeletal pain."
The relationship between chronic pain
and depression is complex and not en-
tirely clear. Pain itself may be the cause
of depressive symptoms by imposing
limits on activities that are intrinsically
rewarding or by altering perceptions of
control over one's life. The reporting of
pain as a symptom of depression, or as
an expression of "masked depression,"
has also been considered, although this
remains controversial. Perceptions of
life control, or more specifically, lack of
control, may be a mediating factor
among CKD patients who develop de-
pression, especially in the context of
chronic pain. The nature of the pain, the
context of its occurrence, and the ways
in which patients cope with pain are

20 Geriatrics February 2007 Volume 62, Number 2 www.geri.com


Ukely central to understanding the great
variability across patients in their abil-
ity to function with pain.
In CKD, pain is often experienced in
the context of multiple, complex symp-
toms and end-of-life issues which may
interfere markedly with psychological,
social and physical coping skills. This
concept is well stated in the term "total
pain," which emphasizes the contribution
of psychological (anxiety and depres-
sion), spiritual (search for meaning and
purpose), social (isolation and abandon-
ment), and fmancial (fear of burdening
the family) factors to the pain experi-
ence. Psychosocial, financial, and spir-
itual issues enter into a cycle of inter-
acting with and perpetuating physical
symptoms and suffering of the patient.
The pain threshold and response to pain
therapy may largely depend on these pa-
tient-related factors rather than the po-
tency of analgesics.^"'^'
Although the causal link between
chronic pain and depression is not clear,
the presence of a psychiatric disorder
has been shown to complicate treat-
ment and rehabilitation of patients with
chronic pain in other patient popula-
tions.^^ The clinical implication is that
health care providers need to pay more
attention to diagnosing and treating de-
pression along with other psychoso-
cial and spiritual issues if they are to
provide adequate pain management.
Conversely, attention to pain assess-
ment and management will likely have
a significant positive impact on depres-
sive symptomatology and mental
HRQL in these patients.
Symptom assessment in CKD
Given the high burden of symptoms,
regular screening for physical and men-
tal symptoms must be incorporated into
routine care for patients with CKD.
The modified Edmonton Symptom As-
sessment System (ESAS) is a reliable,
valid, simple and useful method for
regular screening of physical and psy-
chological symptoms in this patient
population and can even be used effec-
www.geri.com
tively with geriatric patients near the
end of life.^ It consists of 10 visual ana-
log scales with a superimposed 0-10
scale for pain, activity, nausea, depres-
sion, anxiety, drowsiness, appetite,
well-being, and shortness of breath,
and pruritis. The scale for each symp-
tom is anchored by the words "No" and
"Severe" at 0 and 10, respectively. The
assessment and management of chronic
pain is beyond the scope of this review
and have recently been reviewed else-
where.'^'^•' However, several essential
components of this process are out-
lined in table 2.
Several instruments are helpful in
the diagnosis and monitoring of de-
pression in the general population.
These include clinical impression, self-
reports, the BDI, the multiple affect
should be
incorporated into
routine care for
patients with CKD
adjective checklist, and the DSM IV-
TR. However, their use in advanced
CKD can be problematic as the com-
mon somatic symptoms, such as fa-
tigue, anorexia, and changes in sleep
patterns in depression, mimic those
found in CKD. CKD patients, there-
fore, tend to score higher than estab-
lished norms, and it has been suggested
that elevated cut-off scores for depres-
sion should be used.
The BDI has been used extensively
in CKD and is a useful clinical screen-
ing tool. The BDI assesses physiologi-
cal symptoms of depression (eg, weight
February 2007 Volume 62, Number 2 Geriatrics
PSYCHIATRIC CONSULTANT
and appetite changes, sleep disturbances,
fatigue, and loss of energy) in addition
to alterations in affect and cognitive
processes. Despite this, a BDI score of
>!5 has been shown to have a high di-
agnostic sensitivity and specificity for
major depression in dialysis patients.^''
The cognitive Depression Index (CDI)
is a subscale of the BDI in which the so-
matic items have been deleted. Because
it is less confounded by the effects of
physical illness, it may be more helpful
as a screening tool for depression in CKD
prior to fuller diagnostic interviewing.
Like the BDI, CDI scores are associated
with mortality in CKD.^^ Although the
Geriatric Depression Scale (GDS) has
not been used in CKD it may be an ap-
propriate tool for this population since
it has been validated for the elderly, is not
particularly dependent on physical
symptoms of depression, and is avail-
able in many languages.
Treatment of depression in CKD
It is typically recommended that de-
pression in patients with CKD be
treated because of the dramatic impact
of depression on HRQL and its poten-
tial adverse effects on the management
of CKD.26 Further, treatment of de-
pression with antidepressants has been
shown to improve HRQL.^^ When a
pain syndrome and a depressive disor-
der occur together, it is usually neces-
sary to treat these disorders concur-
rently for any lasting relief from chronic
pain to occur, even if the pain and de-
pression are unrelated. If depression is
moderate or severe, it may complicate
the treatment of chronic pain and inter-
fere with the patient's ability to cope
with pain. There are, however, a mi-
nority of patients with severe depres-
sion accompanied by suicidal ideation,
in which pain treatment must be de-
layed until the depressive disorder has
been treated or for whom the concur-
rent treatment should take place in an
inpatient setting.
The underrecognition and inade-
quate treatment of depression in CKD
21
PSYCHIATRIC CONSULTANT
is due, in part, to the lack of training and
experience in psychiatric care, as well
as a poor understanding of the con-
tributing factors for depression in CKD.
Psychiatric disorders, especially de-
pression, may be unrecognized at the
beginning of dialysis as depressive
symptoms such as fatigue, irritability,
apathy, anorexia, and inability to con-
centrate may be attributed solely to ure-
mia. Patients can also hinder the timely
diagnosis and management of depres-
sion. Many patients with chronic pain
become defensive about discussing psy-
chological symptoms and may deny
them altogether, believing that an ac-
knowledgement of such symptoms
would suggest that their pain is caused
by psychological factors. In addition,
chronic pain and depression are fre-
quently misdiagnosed and undertreated
in the elderly due to false assumptions
by health professionals and patients that
both are normal consequences of aging,
a concern with polypharmacy, and the
misconception that the elderly do not
respond well to either pharmacological
or psychological treatment approaches.
The optimal approach to depression
in the general population combines
concomitant psychological therapy and
medication. Although management of
depression in CKD may be similar,
emphasis should be placed on concomi-
tant symptom management, an under-
standing of the unique challenges faced
by elderly CKD patients, especially
those nearing or on dialysis, and the
changes in pharmacokinetics and phar-
macodynamics of psychotropic drugs
in CKD. Patients with CKD not only
have decreased renal clearance of the
parent drug and metabolites, but may
have altered absorption, increased vol-
ume of distribution, and reduced pro-
tein binding leading to increased avail-
able drug levels. Therefore, pharma-
cologic therapy should be closely mon-
itored for therapeutic and toxic effects.
Selective serotonin re-uptake in-
hibitors (SSRIs) and tricyclic antide-
pressants (TCAs) are effective antide-
22 Geriatrics February 2007 Volume 62, Number 2
pressants in CKD.^*-^^ Although often
used in CKD, SSRIs have not been sys-
temically researched.
SSRIs are hepatically metabolized
by the cytochrome P-450 enzyme sys-
tem and the metabolites are excreted
principally by the kidneys. Only small
percentages of the parent drugs are ex-
creted unchanged in the urine. Fluox-
etine is the best-studied medication in
this class and appears to be both non-
toxic and efficacious.^^ Renal function
does not significantly alter fluoxetine
or norfiuoxetine serum levels. Like flu-
oxetine, sertraline and citalopram are
widely prescribed and kinetics appears
minimally changed in patients with
CKD. Interestingly, plasma concentra-
u mm Eiime
depressive
symptoms can be
significantly
reduced
tions of paroxetine hydrochloride are
increased in CKD patients.'^
Dose adjustment is probably not nec-
essary in mild-moderate kidney fail-
ure. However, because of the possibil-
ity of accumulation of active metabo-
lites, it is recommended that these
agents be initiated at low doses (about
half the usual starting dose) with care-
ful titration for elderly patients and
those with ESRD.^^'^"
The literature suggests depressive
symptoms can be significantly reduced
in CKD by low doses of SSRIs.^ In ad-
dition, the SSRIs tend to have relatively
mild side-effect profiles, even in CKD,
although they can be associated with
sexual dysfunction, which is already
compromised in CKD.'^ Care must be
taken with patients receiving concur-
rent drugs metabolized by the cy-
tochrome P-450 enzyme system (eg,
tacrolimus, cyclosporine) when using
antidepressants, which are inhibitors
of these isoenzymes.
Tricyclic antidepressants (TCAs)
(eg, imipramine, amitriptyline) are ef-
fective for analgesia in neuropathic
pain and are frequently prescribed in
low doses for this indication in dialy-
sis patients. However, their use for the
management of depression should be
reserved for treatment-resistant depres-
sion unless there is an additional indi-
cation (eg, painful peripheral neuropa-
thy, insomnia). TCAs are metabolized
in the liver and the metabolites excreted
via the kidney. The hydroxylated
metabolites of TCAs contribute to the
therapeutic and toxic effects in CKD.
Although it is not absolutely neces-
sary to reduce the dose for patients with
CKD,^' TCAs are not well tolerated in
the elderly or those with CKD due to
the anticholinergic, histaminergic and
adrenergic properties resulting in symp-
toms such as urinary retention, dry
mouth, orthostatic hypotension, and
somnolence, symptoms that already
trouble many CKD patients. In addi-
tion, CKD patients show greater un-
predictability and interpatient variabil-
ity in their response to TCAs. TCAs
are also highly protein bound with a
large apparent volume of distribution,
therefore are not effectively removed
by dialysis. If TCAs are to be used, it
has been suggested that they be initi-
ated at low doses, given in divided daily
doses, and titrated slowly until a ther-
apeutic or toxic effect is seen.^*
Several antidepressant medications
should be used with caution or avoided.
The serotonin-norepinephrine reup-
take inhibitors (SNRIs) such as ven-
lafaxine and the norepinephrine
dopamine reuptake inhibitor (NDRI)
bupropion hydrochloride, along with
their metabolites, are eliminated pri-
marily in the urine and lower doses are
required in CKD.^^In addition, clini-
cal experience with these other classes
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of antidepressants is lacking in CKD.
For the relatively few bipolar patients
on dialysis who require lithium, treat-
ment involves administration of a sin-
gle dose (usually 600 mg) after each
dialysis run. Because lithium is a small
molecule that is readily dialyzed,^^
serum lithium levels obtained before
and after dialysis sessions are required
to establish the therapeutic dose.
Summary
Elderly patients with CKD have a high
symptom burden. Chronic pain and
clinical depression is widespread in
this patient population and unfortu-
nately often unrecognized and un-
treated by health care professionals.
Routine screening and more vigorous
treatment of physical and mental symp-
toms, especially chronic pain and de-
pression, is required. The use of a sim-
ple, standardized, self-report tool, such
as the modified ESAS, is ideal for ini-
tial symptom screening. Because de-
pressive disorders are an integral part
of the experience of chronic pain, pa-
tients with chronic pain should be care-
fully evaluated as pain is unlikely to
be controlled unless these associated
symptoms or unmet needs are ad-
dressed. Constant reassessment is nec-
essary: as you treat one symptom suc-
cessfully, others may improve allow-
ing for successful weaning of therapy.
For example, when pain and functional
limitations are successfully addressed,
the symptoms of depression may im-
prove. This approach to chronic pain
and depression has the potential to dra-
matically improve elderly CKD pa-
tients' HRQL. 8
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