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Australian and Newhttp://anp.sagepub.com/
Zealand Journal of Psychiatry

Depression and chronic kidney disease: A review for clinicians

Alison Bautovich, Ivor Katz, Michelle Smith, Colleen K Loo and Samuel B Harvey
Aust N Z J Psychiatry published online 21 March 2014
DOI: 10.1177/0004867414528589

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research-article2014
ANP0010.1177/0004867414528589Australian & New Zealand Journal of PsychiatryBautovich et al.

Review

Australian & New Zealand Journal of Psychiatry

Depression and chronic kidney disease: 1­–12

DOI: 10.1177/0004867414528589

A review for clinicians © The Royal Australian and

New Zealand College of Psychiatrists 2014
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Alison Bautovich1,2,3, Ivor Katz3,4, Michelle Smith1,5, Colleen K

Loo1,3,6 and Samuel B Harvey1,3,6

Abstract
Objective: To review the recent academic literature surrounding the prevalence, aetiopathology, associations and
management of depression in chronic kidney disease (CKD), in order to provide a practical and up-to-date resource for
clinicians.
Methods: We conducted electronic searches of the following databases: MEDLINE, EMBASE and PsycINFO. The main
search terms were: depression, mood disorders, depressive disorder, mental illness, in combination with kidney disease,
renal insufficiency, dialysis, kidney failure. Separate searches were conducted regarding antidepressant use in CKD.
Results: A number of recent, large and well-conducted studies have confirmed markedly raised rates of depression
amongst those with CKD, with meta-analysis suggesting the prevalence of interview-defined depression to be approxi-
mately 20%. The interactions between depression and CKD are complex, bidirectional and multifactorial. Depression in
CKD has been shown to be associated with multiple poor outcomes, including increased mortality and hospitalisation
rates, as well as poorer treatment compliance and quality of life. Clinical evaluation of depression in patients with CKD
can be challenging; however, once a diagnosis is made, a range of treatment modalities can be considered.
Conclusions: Depression is common in CKD and is associated with a significant risk of adverse outcomes. Given the
importance of this issue, there is now an urgent need for well-conducted randomised trials of interventions for depres-
sion in CKD in order to provide information on the safety and efficacy of treatments.

Keywords
Antidepressive agents, depression, dialysis, kidney disease, mental illness, renal failure

Introduction
Until recently, the bulk of the academic literature around
the overlap between chronic physical illness and mental
health has tended to focus on cardiovascular disease
and depression. However, there have been a number
of large studies published which suggest that the asso-
ciation between depression and several other chronic
somatic conditions, including renal disease, are equally
important.
Chronic kidney disease (CKD) is a growing problem
It is well established that depression is more common
amongst those with chronic physical health problems
(Harvey and Ismail, 2008; Olver and Hopwood, 2012;
1School of Psychiatry, University of New South Wales, Sydney, Australia
2NSW Institute of Psychiatry, Westmead, Australia
3St George Hospital, Kogarah, Australia
4Faculty of Medicine, University of New South Wales, Sydney, Australia
5Prince of Wales Hospital, Randwick, Australia

that affects approximately 10% of the global population 6Black Dog Institute, Sydney, Australia

(Palmer et al., 2013b). Most of the data on depression in

CKD have focused on end-stage kidney disease (ESKD), Corresponding author:
Alison Bautovich, School of Psychiatry, University of New South Wales,
which is defined when there is permanent kidney failure Black Dog Institute Building, Hospital Road, Randwick, NSW 2031,
requiring regular renal replacement therapy (dialysis or Australia.
transplant). Email: a.bautovich@unsw.edu.au

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 2 ANZJP Articles
Rayner et al., 2010). However, depression amongst those
with CKD has been estimated to be even greater than that
reported for patients with other chronic diseases (Palmer
et al., 2013b). Furthermore, depression in CKD has been
shown to be associated with multiple poor outcomes
(Chilcot et al., 2011; Hedayati et al., 2010; Kimmel et al.,
2000; Koo et al., 2005; Palmer et al., 2013a). Unfortunately,
despite these associations and the increasingly available evi-
dence, clinicians remain cautious when managing depres-
sion in those with CKD, and rates of detection and treatment
remain very low (Hedayati and Finkelstein, 2009).
This review will discuss the prevalence of depression in
patients with CKD, propose a model for the complex inter-
actions between depression and CKD, highlight the impor-
tant consequences of comorbid depression, and, finally,
synthesise the available evidence in order to provide guid-
ance to clinicians for the appropriate management of
depression in this population. As the bulk of the research to
date has been in those with ESKD, this will be the primary
focus of this review.
Review methodology
Electronic searches were conducted using title and subject
headings for ‘depression’, ‘mood disorders’, ‘depressive
disorder’, ‘mental health’, ‘mental illness’ and ‘psychiat-
ric’, in combination with ‘kidney disease’, ‘renal dialysis’,
renal insufficiency’ and ‘kidney failure’. The search was
conducted up to and including 28 March 2013, and was
limited to those papers written in English.
While not producing clinical management guidelines as
such, this review aims to summarise the evidence regarding
depression in CKD in order to aid clinical decisions. One
issue which can be particularly challenging for clinicians is
the use of antidepressant medications in the setting of CKD.
A separate search was conducted to identify studies exam-
ining the efficacy and pharmacokinetics for antidepressants
in the setting of impaired renal function. This, together with
previous guidelines (Taylor et al., 2012) was used to pro-
vide recommendations on the safety of a range of com-
monly prescribed antidepressants. Each antidepressant was
classified into one of three categories: ‘evidence available
suggests agents are usually safe to use, but may require
additional monitoring and dose alteration’, ‘evidence avail-
able suggests can be used in CKD, but greater caution
needed’, or ‘not recommended for routine use in CKD’. In
order to be classified in the first category, an antidepressant
had to have published evidence of efficacy in CKD and not
have any major or common adverse effects likely to be par-
ticularly problematic in renal disease.
Epidemiology
Attempts to quantify the prevalence of depression in CKD
using self-report scales have often produced widely varying
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ANP528589.indd 2
estimates. Palmer et al. (2013b) recently conducted a sys-
tematic review and meta-analysis of studies to summarise
the point prevalence of depressive symptoms in adults with
CKD. A total of 249 populations were included (55,982
participants) and analyses were limited to studies that used
clinical interview and pre-specified criteria for diagnosis.
The authors found the summary prevalence of interview-
defined depression to be 20.3%. Using self or clinician-
administered rating scales, the prevalence of depressive
symptoms for CKD was higher, suggesting that self-report
scales may overestimate the presence of depression, par-
ticularly in the renal setting. The frequency of somatic
symptoms commonly experienced in these patients, such as
fatigue, sleep disturbance and decreased appetite, may
partly explain this overestimate.
Table 1 attempts to place these prevalence rates in the
context of other chronic medical illnesses. This table shows
the rates of interview-defined depression, using either
structured or semi-structured interviews that have been
observed in other clinical settings. Prevalence rates of
depression were obtained from meta-analyses or systematic
reviews, where available.
Why is depression more common
in CKD?
The complex interactions between depression and CKD are
dynamic and multifactorial. In discussing the relationship
between depression and CKD, it is helpful to consider
shared ‘upstream’ risk factors, as well as the biopsychoso-
cial or ‘downstream’ consequences of both illnesses. This is
illustrated in Figure 1 using a model adapted from that orig-
inally proposed by Katon (2011), which can be applied to
many chronic diseases.
Both childhood adversity and socioeconomic factors are
some of the most important risk factors for depression
(Hatch et al., 2010; Lorant et al., 2003). Socioeconomic
adversity is also associated with adverse health behaviours
such as smoking, poor diet and sedentary lifestyle, as well
as delayed help-seeking for established health problems.
These factors increase the risk of, and impair the manage-
ment of, diabetes and cardiovascular disease, as well as
increasing the risk of depression (Harvey et al., 2010;
Rivenes et al., 2009). As diabetes and cardiovascular dis-
ease are common causes of renal impairment, the impor-
tance of these socioeconomic and lifestyle factors cannot
be overlooked.
There are other biological elements that can be consid-
ered to be both part of the shared ‘upstream’ risk factors, as
well as consequences of CKD and depression. These include
the immune system, inflammatory pathways, disturbances
of the hypothalamic pituitary axis and changes in the para-
sympathetic and sympathetic nervous systems (Ahrens
et al., 2008; Raison et al., 2006; Zunszain et al., 2013). One
biological element that has been suggested as being
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 Bautovich et al. 3

Table 1.  Prevalence of interview-defined depression in a variety of chronic medical illnesses.

Chronic illness Prevalence of depression Source of prevalence estimate

Chronic kidney disease 20.3% (CI 17.5–23.5) Meta-analysis of 5105 participants using diagnostic criteria by clinical
interview (Palmer et al., 2013b)

Acute myocardial infarction 19.8% (CI 19.1–20.6) Meta-analysis of eight studies using standardised interview in patient
hospitalised for acute myocardial infarction (Thombs et al., 2006)

Cancer 16.3% (CI 13.4–19.5) Meta-analysis including 66 studies of syndromal depression evaluated
using interview-based diagnosis (Mitchell et al., 2011)

Epilepsy 13.2% (CI 11.07–15.68) Results from one available study using a standardised interview to
diagnose current depression (Fiest et al., 2013)

COAD 27.6% (CI 21.2–35.2) Meta-analysis included two studies using clinical interview-defined
depression (Zhang et al., 2011)

Diabetes Meta-analysis included 14 studies using diagnostic interview to define

  Type I: 13.6% depression (Anderson et al., 2001)
  Type II: 10.9%

COAD: chronic obstructive airways disease.

Figure 1.  Complex relationship between chronic kidney disease and depression.

Lifestyle and Socioeconomic Factors

• Low socioeconomic status associated with
development and progression of both CKD and
depression
• Also good evidence for sedentary lifestyle and poor diet
being associated with increased risk of depression and
renal disease
Shared risk
factors
Biological risks
• Subtle changes in inflammation and immune function
postulated as being part of aetiological pathways for
both depression and CKD

Chronic
Kidney Depression
Disease (CKD)

Biological consequences
• Increased inflammation as a consequence of
depression and often reported in those with CKD

Negative self care behaviours

• Those with depression less likely to comply with Biopsychosocial
medication, dialysis and renal diet. CKD associated
with a sedentary lifestyle, which is an independent risk consequences
factor for depression of both illnesses

Symptom burden
• Those with CKD have increased fatigue, regular
dialysis and sleep disturbance which all increase the
risk of subsequent depression

Loss
• Those with CKD report loss of role, identity, body
image and employment, which all increase the risk of
depression

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 4 ANZJP Articles
particularly relevant for understanding the bidirectional link
between CKD and depression is inflammation. Higher con-
centrations of pro-inflammatory cytokines have been identi-
fied among clinically depressed individuals and those with
symptoms of depression, although there is considerable het-
erogeneity between studies (Dowlati et al., 2010; Howren
et al., 2009). Furthermore, there is evidence to suggest that
these pro-inflammatory cytokines interact with many of the
pathophysiological mechanisms of depression, including
neurotransmitter metabolism, neuroendocrine function,
synaptic plasticity and behaviour (Raison et al., 2006). CKD
is often considered to be a pro-inflammatory state with
increased inflammatory markers and oxidative stress
(Himmelfarb, 2008; Stenvinkel and Alvestrand, 2002),
although attempts to demonstrate this have been somewhat
mixed. This chronic pro-inflammatory state is thought to be
related to the higher than expected rates of cardiovascular
disease and other causes of increased mortality in this popu-
lation (Kimmel et al., 1998b; Stenvinkel et al., 2005). It is
possible that these factors could also partly explain the high
rates of depression seen in this population.
Finally, loss is an important psychological theme to con-
sider in examining depression in those with CKD. In a
study of 151 ESKD patients, perceptions of loss were the
strongest predictors of depression, which in turn predicted
the quality of life (QOL) (Chan et al., 2009). In the early
stages of CKD, people may feel a loss of wellness, as well
as the more practical losses relating to lifestyle and inde-
pendence. Loss of identity and primary role function are
also important areas to consider. Those on dialysis often
dislike, or have ambivalent feelings towards the treatment;
being dependent on such treatment for life, while having to
endure a loss of autonomy and control. Additionally, these
factors may contribute to patients with CKD having feel-
ings of guilt for the burden they perceive they cause for
family members and carers. Not surprisingly, self-concept
and self-esteem may be challenged.
Why does depression in CKD matter?
Accumulating evidence has shown that clinical depression
and subthreshold depressive symptoms are associated with
an increased risk for adverse clinical outcomes in patients
with CKD. These negative outcomes include increased
mortality and rates of hospitalisation, poor adherence to
treatment and decreased QOL.
Mortality
The relationship between ESKD and survival has been
somewhat controversial. Studies from the 1980s suggested
that depression did significantly predict mortality in ESKD
patients. However, as Halen et al. (2012) highlight, these
studies used relatively small sample sizes and had some
methodological limitations. Some later studies (Koo et al.,
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2003; Watnick et al., 2003), using more standardised meas-
ures for depression and advanced statistical methods, have
failed to demonstrate an effect of depression on all-cause
mortality in ESKD patients.
The Cochrane Renal Group have recently completed a
systematic review and meta-analysis that helps to clarify
this issue of depression and mortality in CKD (Palmer
et al., 2013a). This paper included 22 cohort studies (83,381
participants) of depressed adults with CKD. Overall, a
strong and statistically significant association was found
between depression status and risk of all-cause mortality
(RR 1.59; 95% CI: 1.35–1.87). These results remained con-
sistent across stages of CKD, regardless of sex or age.
Furthermore, the excess mortality risk attributable to
depression in CKD is higher than that seen in other chroni-
cally diseased populations, such as cancer, diabetes and
heart disease (Palmer et al., 2013b).
Hospitalisation
Multiple studies have shown that depression is associated
with increased healthcare costs, including primary, phar-
macy, inpatient medical, inpatient psychiatric and outpa-
tient mental health care (Katon, 2011). DOPPS (The
Dialysis Outcomes and Practice Patterns Study) was a
large, international, prospective, observational study of
5256 haemodialysis patients which found that, after adjust-
ing for time on dialysis, age, race, socioeconomic status,
comorbid indicators and country, depression was associ-
ated with an increased risk for first hospitalisation (Lopes
et al., 2002). Hedayati et al. have also conducted several
studies attempting to address the association between
depression and a variety of negative health outcomes in
renal disease, including dialysis initiation, hospitalisation
rates and length of stay, and death. In each of these studies
an association between depression and hospitalisation has
been shown (Hedayati et al., 2005, 2008, 2010).
Adherence
Treatment non-adherence represents one of the potential
pathways through which depression may affect mortality
and morbidity in patients with CKD. Treatment compliance
in CKD patients is quite complex, with patients having to
comply not only with the dialysis schedule, but also pre-
scribed medication and dietary regimens.
Measuring adherence in ESKD patients presents partic-
ular logistical difficulties (Chilcot et al., 2010); however,
most studies have indicated a relationship between depres-
sive affect and both laboratory and behavioural markers of
poor compliance in the dialysis patient (Kaveh and Kimmel,
2001; Koo et al., 2003; Leggat, 2005; Rosenthal Asher
et al., 2012). Depressive symptoms of low motivation,
impaired concentration and memory, and apathy can sig-
nificantly interfere with patients’ adherence to complex and
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 Bautovich et al. 5
challenging treatment plans. This is important, as decreased
behavioural adherence (skipping dialysis sessions, shorten-
ing dialysis time) has been shown to be associated with
decreased survival (Kimmel et al., 1998a; Rosenthal Asher
et al., 2012).
Adherence to a dietary prescription is a particular area of
importance as nutritional status has been shown to signifi-
cantly impact the course and outcome of ESKD. Depression
is associated with impaired nutrition in dialysis patients
(Koo et al., 2003, 2005), with non-adherence rates to pre-
scribed diet and fluid restriction recommendations of
approximately 50% (Kugler et al., 2005). Importantly, anti-
depressant therapy in conjunction with supportive psycho-
therapy appears to improve nutritional status in depressed
individuals with CKD (Koo et al., 2003, 2005).
Finally, depressed individuals on dialysis therapy are
also significantly more likely to withdraw from treatment
(Lacson et al., 2012; McDade-Montez et al., 2006) than
non-depressed dialysis patients.
Quality of life
It is now widely accepted that health-related quality of life
(HRQOL) is significantly compromised in patients with
ESKD (Soni et al., 2010). Furthermore, HRQOL has been
associated with increased morbidity and mortality.
Depression has been found to have a profound negative
impact on HRQOL in CKD patients (Kimmel, 2000;
Weisbord et al., 2005). Additionally, it has been proposed
that depression and anxiety may be more strongly associ-
ated with HRQOL in CKD than clinical and socio-demo-
graphic variables taken together (Vazquez et al., 2005).
Depression can impact on HRQOL in a number of ways.
Patients with depression have been found to have two- to
threefold more medical symptoms compared with controls
without depression (Katon, 2011). In addition to this higher
symptom burden, ESKD patients with depression also
experience more fatigue, cognitive difficulties, pain, sleep
disturbances, sexual dysfunction and relationship difficul-
ties (Soni et al., 2010). Aside from increased levels of
symptoms, depression is also linked with reduced func-
tional performance and increased rates of occupational dis-
ability (Harvey et al., 2011; Knudsen et al., 2013), often
leading to financial strain and reduced well-being.
HRQOL is important in and of itself; however, as both
HRQOL and depression are related to survival in dialysis
patients (Hedayati et al., 2008; Kimmel, 2000; Mapes et al.,
2003), this negative association has a clear clinical
importance.
Clinical aspects of depression in CKD
Depression is often underdiagnosed in patients with serious
physical illness and CKD is no exception. Dialysis physi-
cians and nurses often fail to recognise symptoms of
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depression (Feroze et al., 2010). There may be many rea-
sons for this, including a lack of knowledge or confidence
when asking about mental health symptoms, as well as a
focus, both from the medical staff and the patients, on phys-
ical symptoms alone. Although it has been shown that
somatic symptoms are frequently the presenting complaint
of those with a chronic medical illness who are eventually
diagnosed with depression, physicians often pay less atten-
tion to somatic complaints of psychiatric illness (Farrokhi,
2012). An additional problem is the overlap between the
physical symptoms of depression and those of the underly-
ing medical illness. This is critical to the clinical evaluation
of a patient with ESKD. In particular, the depressive symp-
toms of psychomotor agitation or retardation, appetite and
weight changes, sleep disturbance, and aches and pains are
often difficult to distinguish from anorexia, sleep distur-
bance and neuropathy secondary to underlying ESKD, par-
ticularly when uraemia is present (Halen et al., 2012).
Other factors to consider in evaluating the potential
diagnosis of depression in a patient with ESKD include
anaemia, electrolyte disturbances, side effects from medi-
cation and symptoms from other systemic illnesses. It is
generally recommended that the diagnosis of depression in
a patient with comorbid CKD should rely more heavily on
psychological features, such as anhedonia, guilt, loss of
self-esteem, hopelessness and suicidal ideation (Hedayati
et al., 2012). Structured clinical interviews allow for a more
thorough examination of the patient’s cognitive set, and as
such are considered the gold standard method for distin-
guishing depressive symptoms from somatic complaints.
Screening
The issue of screening for depression in CKD has been
somewhat controversial. Some, such as Palmer et al.
(2013b), assert that there is insufficient high-quality data
available to show that screening for, or treatment of, depres-
sion in CKD populations improves clinical symptoms and
QOL. Farrokhi (2012) also suggests that before screening
programs for depression in CKD are recommended, the
benefits and harms of psychiatric intervention in this popu-
lation need to be evaluated.
However, others, such as Hedayati and Finkelstein
(2009), argue for routine screening based on the high preva-
lence of depression and associated poor outcomes in this
population. Zalai asserts that, although routine screening for
depression per se might not lead to better outcomes, it may
help identify people whose psychosocial distress would oth-
erwise remain undetected (Zalai et al., 2012). Hedayati has
suggested that screening for depression should take place at
key points of transition, such as on the initial evaluation of
the CKD patient, at dialysis initiation, and then at regular
intervals thereafter (Hedayati et al., 2012).
Several scales have been validated against Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition
Australian & New Zealand Journal of Psychiatry
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 6 ANZJP Articles
(DSM-IV)-structured interviews among patients with CKD
and ESKD, including the Beck Depression Inventory
(BDI), the Hospital Anxiety and Depression Scale (HADS)
and the Center for Epidemiologic Studies Depression Scale
(CES-D). However, because of the overlap between the
symptoms of depression and CKD, the cut-off scores sug-
gested when screening depressive symptoms in the CKD
population are generally the same or higher than those used
in the general population. For example, when using the
BDI, the recommended cut-off score to define clinically
significant depression in the general population is 11 or
greater (Beck et al., 1988); however, a cut-off of 11 or
higher (Hedayati and Finkelstein, 2009) and between 14
and 17 (Hedayati et al., 2006; Preljevic et al., 2012) is sug-
gested for the CKD and ESKD populations, respectively.
Management
Despite the high prevalence of depression and its association
with poor outcomes, only a minority of patients with ESKD
are given a diagnosis of, or receive treatment for, depression
(Hedayati and Finkelstein, 2009). This may in part be due to
the limited systematic study in this area, with only six small
randomised controlled trials (RCTs) available to guide treat-
ment safety and efficacy (Ancarani, 1993; Baines et al.,
2004; Blumenfield et al., 1997; Duarte et al., 2009; Koo
et al., 2005; Lii et al., 2007). The following section reviews
what pharmacological and non-pharmacological approaches
are available for the management of depression in CKD.
Pharmacological treatment
Depression in CKD is often undertreated. In their 2006
study using a DSM-IV-validated interview, Hedayati et al.
(2006) found that less than half of the depressed patients
with ESKD were being treated with antidepressants and
about half of those on drug treatment were receiving sub-
therapeutic doses. Undertreatment of depression and under-
dosing of antidepressant agents may be in part caused by
physicians’ concerns regarding efficacy and adverse effects.
Little research has been performed regarding the safety of
antidepressant medication use in patients with CKD, with
such patients often being excluded from trials because of
concerns for safety. In fact, to date, there has been only one
completed RCT of antidepressant medication in CKD
(Blumenfield et al., 1997). This was a small trial of 14
chronic haemodialysis patients with major depression. A
statistically significant improvement in depression was
found after 4 weeks amongst those given fluoxetine; how-
ever, this was not sustained at 8 weeks. Non-randomised,
observational studies (Ancarani, 1993; Baines et al., 2004;
Blumenfield et al., 1997; Duarte et al., 2009; Koo et al.,
2005; Lii et al., 2007) suggest that antidepressant medica-
tion may be useful in CKD; however, further studies are
needed.
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Generally, antidepressant medications are hepatically
metabolised, highly protein bound and not removed signifi-
cantly by dialysis (Hedayati and Finkelstein, 2009). Thus,
the relative activity and mode of excretion of metabolites of
these drugs in patients with CKD is often uncertain. Further
concerns include an increased risk of drug interactions
(monoamine oxidase inhibitors, tricyclics and selective
serotonin reuptake inhibitors (SSRIs)) (Cohen et al., 2004;
Hedayati and Finkelstein, 2009), anticholinergic effects,
including urinary retention (tricyclics) (Cohen et al., 2004;
Hedayati and Finkelstein, 2009), QTc prolongation (tricy-
clics) (Cohen et al., 2004; Hedayati and Finkelstein, 2009),
accumulation of toxic metabolites (venlafaxine and bupro-
pion) (Cohen et al., 2004) and increased risk of bleeding
(SSRIs) (Yuan et al., 2006). Given the limited evidence
base, the decision regarding which antidepressant to use in
those with CKD is based on its pharmacokinetics, drug-to-
drug interactions and adverse event profile. Information
regarding the pharmacokinetics and recommended dosage
alterations for a range of commonly used antidepressants is
provided in Table 2.
Non-pharmacological management
The challenges associated with utilising pharmacological
strategies for the treatment of depression in CKD suggest
effective non-pharmacological treatments may be of par-
ticular use in this population. Examples of non-pharmaco-
logical treatments include electroconvulsive therapy,
cognitive behavioural therapy (CBT), exercise therapy and
changes to the dialysis regimen.
Electroconvulsive therapy (ECT). ECT is a highly effective
treatment for severe depression, including medication-resis-
tant depression (Carney, 2003; Rasmussen et al., 2002). The
use of ECT has not been studied in RCTs in CKD, but there
are case reports of excellent response to ECT in patients
with CKD and severe depression refractory to antidepres-
sant medication (Varghese et al., 2006; Williams and
Ostroff, 2005). Special precautions are required in the CKD
patient, including control of abrupt increases in blood pres-
sure, adequate muscle relaxation to prevent strong contrac-
tions and the subsequent risk of fractures in an osteopenic
patient (Williams and Ostroff, 2005), careful management
of potassium levels which are further increased by succinyl-
choline – a muscle relaxant commonly administered during
ECT (Horton and Fergusson, 1988), and attention to ECT
dose levels, ideally established by individual seizure thresh-
old titration, as the latter may be altered by acidosis and
hypocalcaemia (Varghese et al., 2006).
Cognitive behavioural therapy (CBT). CBT is a well-docu-
mented, evidence-based therapy for the treatment of depres-
sion. Importantly, for those in the general hospital setting,
CBT may also have benefits beyond the treatment of
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 Bautovich et al. 7

Table 2.  Evidence relating to the use of some common antidepressant medications in patients with CKD.

Recommendation
Drug Comments Potential class adverse events for use in CKD

SSRIs Nausea, dyspepsia and

(Hedayati et al., 2012; diarrhoea
Taylor et al., 2012) Headache and insomnia
Citalopram • Less than 15% excreted in urine Increased risk of bleeding 
(Cohen et al., 2004; • Has been shown to treat depression in CKD Agitation and anxiety in early
Hosseini et al., 2012; and improve QOL stages of treatment
Kelly et al., 2003) • Manufacturer does not recommend use if Sexual dysfunction
GFR<20 ml/min Hyponatraemia
• Dose adjustment normally not required in Some (not all) SSRIs
renal impairment, but use with caution when are potent inhibitors of
GFR <10 ml/min cytochrome enzymes which
may lead to drug interactions
Fluoxetine • 5–10% excreted in urine
(Baghdady et al., 2009; • Long half-life 
Blumenfield et al., • If GFR <20 ml/min, consider using on
1997; Levy et al., 1996) alternate days or low dose
• Small study suggested relative safety and
efficacy in ESKD

Sertraline • Less than 1% excreted unchanged in urine 

(Brewster et al., 2003; • Pharmacokinetics in renal impairment are
DeVane et al., 2002) unchanged in single dose studies, but no
published data on multiple dosing
• No dose adjustment required
• Acute renal failure has been reported, so use
with caution

Paroxetine • Less than 2% excreted in urine 

(Doyle et al., 1989; • Increased plasma concentration found when
Koo et al., 2005) GFR <30 ml/min
• If GFR <30 ml/min start at 10–20 mg/day and
increase slowly
• Has been shown to reduce depressive
symptoms in ESKD
• Rarely associated with Fanconi’s syndrome
(acute renal failure)

SNRIs Nausea
(Baghdady et al., Insomnia
2009; Bril et al., 2011; Dry mouth
Hedayati et al., 2012; Sweating
Taylor, 2012) Elevation in blood pressure
Venlafaxine • Clearance decrease and half-life prolonged Sexual dysfunction 
in renal impairment. Avoid slow release Duloxetine is an inhibitor of
formulations if GFR <30 ml/min cytochrome enzymes, which
• GFR 30–50 ml/min: dose as normal or may lead to drug interactions
reduce by 50%
• GFR 10–30 ml/min: reduce dose by 50% and
use standard formulation once daily
• Manufacturer advises to avoid use if GFR
<10 ml/min
• Accumulation of toxic metabolite can occur
and rhabdomyolysis and renal failure have
been reported, but rare
Duloxetine • Duloxetine is contraindicated if GFR <30 ml/ 
min as it can accumulate. If GFR >30 ml/min,
start at low dose and increase slowly
(Continued)

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 8 ANZJP Articles

Table 2. (Continued)

Recommendation
Drug Comments Potential class adverse events for use in CKD

TCAs Sedation
(Bril et al., 2011; Arrhythmias
Hedayati et al., 2012; QTc prolongation
Taylor et al., 2012) Postural hypotension
Confusion in elderly
Amitriptyline • Less than 2% excreted in urine Dry mouth and blurred vision 
• No dose adjustment needed, but start at low Urinary retention
dose and increase slowly
• Plasma level monitoring may be useful

NSA Sedation
(Baghdady et al., 2009; Increased appetite and weight
Hedayati et al., 2012; gain
Taylor et al., 2012) Oedema
Blood dyscrasia
Mirtazapine • 75% excreted unchanged in urine 
• Clearance reduced by 50% in those with
GFR <10 ml/min
• Dose as usual for GFR 10–50 ml/min
• GFR <10 ml/min: start at low dose and
increase slowly
• Has been used to treat pruritis caused by
renal failure

MAOs Need to avoid tyramine in

(Baghdady et al., 2009; food due to association with
Hedayati et al., 2012; hypertensive crisis
Taylor et al., 2012) Postural hypotension
Drowsiness
Phenelzine • No dose adjustment required Potential serious interactions 
• However, usually avoid because of significant with many medications
drug–drug and food interactions

SSRI: selective serotonin reuptake inhibitor; CKD: chronic kidney disease; QOL: quality of life; GFR: glomerular filtration rate; ESKD: end-stage
kidney disease; SNRI: serotonin and noradrenergic reuptake inhibitor; TCA: tricyclic antidepressant; NSA: noradrenergic and specific serotonergic
antidepressant; MAO: monoamine oxidase inhibitor.
Evidence available suggests agents are usually safe to use, but may require additional monitoring and dose alteration.
 Evidence available suggests can be used in chronic kidney disease, but greater caution needed.
 Not recommended for routine use in chronic kidney disease.
The contents of this table represent the views of the authors based on their experience and review of the current literature. They are not intended
and should not be relied upon as recommending or promoting a specific treatment by physicians for any particular patients. The authors make no
representations or warranties with respect to the accuracy or completeness of the contents of this work. The authors will not be liable for any
damages arising herefrom.

depression, including improving medication adherence and
reducing the severity of pain and other symptoms (Lloyd
and Guthrie, 2007). The ability of CBT to change underly-
ing attitudes to illness is also very relevant, given that nega-
tive beliefs regarding underlying illness schemata have
been shown to be associated with higher scores on the BDI
(Ghuzman and Nicassio, 2003).
Although there have been many RCTs of CBT for the
treatment of depression in the physically ill (Berkman et al.,
2003; de Godoy and de Godoy, 2003; Safren et al., 2014),
there is a distinct lack of such trials in the CKD population.
However, the observational studies and the few small RCTs
that are available show mostly promising results. In a recent
study of group CBT (Duarte et al., 2009), 85 dialysis patients
with interview-diagnosed depression were randomly
assigned to standard care versus group CBT with a psychol-
ogist weekly for 12 weeks. After 3 months, a significant dif-
ference in BDI scores was found between treatment and
control groups. Additionally, improvement was found in
several domains on a QOL measure. An interesting study
conducted in Louisiana after hurricanes Katrina and Rita
shows that CBT may not have to be delivered by psycholo-
gists (Weiner et al., 2010). In this study, 22 social workers
implemented a cognitive behavioural intervention to 69

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 Bautovich et al. 9
ESKD patients. Patients who participated in these sessions
showed a significant reduction in depressive symptoms
compared to patients who did not discuss the material.
Exercise therapy. There is increasing evidence of a link
between levels of physical activity and an individuals’
mood (Harvey et al., 2010). In keeping with this emerging
research, it appears that exercise programs, in addition to
their primary aims of optimising physical function, cardio-
vascular risk and efficacy of dialysis, may also have a ben-
eficial effect on depressive symptoms and various measures
of HRQOL in patients with CKD (Greenwood et al., 2012).
In a study (Ouzouni et al., 2009) of 35 haemodialysis
(HD) patients randomly assigned to a 10-month intradia-
lytic exercise training program, a 39% reduction in depres-
sive symptoms (as measured by BDI scores) was found in
the exercise group compared to the control group.
Additionally, another study (Kouidi et al., 2010) of 24 hae-
modialysis patients randomised to a 1-year intradialytic
exercise training program showed a BDI score decrease of
34.5% (p < 0.001). Greenwood et al. (2012) conducted a
larger, albeit uncontrolled, study of 131 participants at vari-
ous stages of CKD, and showed that there was a significant
improvement in symptoms of depression (29%) following
a 12-week renal rehabilitation exercise program. However,
this study also illustrates one of the main problems with
exercise therapy, with only 55% of participants regularly
completing the exercise program.
Change in dialysis regimen.  It is not clear whether increasing
the frequency of dialysis improves depression rates. The
Following Rehabilitation, Economics and Everyday-Dialy-
sis Outcome Measurements (FREEDOM) study (Jaber
et al., 2010) was an observational cohort study with 128
completers. Dialysis frequency was increased from the stan-
dard three times weekly to six times weekly, with a targeted
standardised weekly KT/V – a measure of dialysis adequacy
– of greater than 2.1. At the end of the trial, a significant
decrease in BDI values was found, and this was sustained at
12 months. However, the results of the intention-to-treat
analysis were less clear. Additionally, it is important to note
that this study did not have a control group, and participants
were found to have had an increase in prescribed antidepres-
sant use during the study. A recent, large, randomised trial
(Group et al., 2010) did not find a statistically significant
difference in BDI scores after a 12-month period of six
times per week HD versus the conventional three times per
week, although scores were lower in the six times per week
group. It is difficult to determine if these lower scores are
due to expected improvements in somatic symptoms sec-
ondary to more frequent dialysis, or are true improvements
in depressive symptoms.
Others.  Given the magnitude of the problem of depression
in patients with CKD, additional therapeutic approaches
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ANP528589.indd 9
need to be examined. Marriage and family tensions in CKD
patients are well documented (Daneker et al., 2001). Inter-
ventions that address these relationship issues need to be
explored, using, for example, family and marital counsel-
ling. Additionally, building up meaningful social supports,
through the involvement of community, leisure or religious
organisations, may help (Hedayati et al., 2012), both for the
patient and caregivers. This is important as caregiver bur-
den and burnout can be a major problem in long-term debil-
itating conditions like CKD. A Cochrane analysis also
suggested that music therapy can have a beneficial impact
on depressive symptoms (Maratos et al., 2008). Impor-
tantly, patient acceptance of this therapy was high, with
dropout rates being low in all five studies included in the
analysis.
Future directions could also include further exploration
of inflammation in CKD. Data suggest that the reduction in
cytokine activation associated with inflammatory condi-
tions alone, without the use of antidepressant medications,
can result in amelioration of depressive symptoms (Tyring
et al., 2006). Additionally, novel brain stimulation treat-
ments, such as repetitive transcranial magnetic stimulation
(Slotema et al., 2010) and transcranial direct current stimu-
lation (tDCS) (Berlim et al., 2013; Loo et al., 2010) also
show promise in the treatment of depression. Such tech-
niques may be of particular use in patients in whom phar-
macological treatment of depression is a particular
challenge.
Conclusions
Depression is a very common but complex problem
amongst those individuals with CKD. Recent research
reports provide strong evidence that around one in five
patients with ESKD will be suffering from depression.
Given that comorbid depression has been associated with
higher rates of mortality, increased hospitalisation, reduced
treatment adherence and lower QOL, the identification and
appropriate treatment of depression in those with CKD is
extremely important and needs to be given greater priority.
However, the overlap of symptomatology makes diagnos-
ing depression in the setting of CKD challenging, and the
evidence base for effective treatments is lacking. Given the
size and importance of this issue, there is now an urgent
need for well-conducted randomised trials for interventions
focused on the treatment of depression in CKD in order to
provide information on their safety and efficacy. However,
despite the lack of available data to date, a range of pharma-
cological and non-pharmacological treatment modalities
are available and should be considered in this population.
Acknowledgements
The authors are grateful to Anne Connolly, principal pharmacist at
the South London and Maudsley NHS Foundation Trust, for her
assistance in the construction of Table 2.
Australian & New Zealand Journal of Psychiatry
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 10 ANZJP Articles
Funding
Dr Bautovich was funded by a grant from the New South Wales
Institute of Psychiatry. The research was also assisted by a grant
from the Royal Australian and New Zealand College of
Psychiatrists.
Declaration of interest
All authors have completed the Unified Competing Interest form
at www.icmje.org/coi_disclosure.pdf and declare that: (1) AB
received support from the New South Wales Institute of Psychiatry
and the Royal Australian and New Zealand College of Psychiatrists
for the submitted work; (2) CL has received financial support
from the Stanley Medical Research Foundation to fund research
into tDCS treatment in depression and honoraria from Astra-
Zeneca for speaking at an ECT conference; IK has received pay-
ments as a consultant for National Renal Care and has received
grants from, and sits on, the Chronic Kidney Disease Advisory
Panel for Amgen; and (3) CL has had tDCS equipment donated
from Soterix as part of other ongoing research; IK is a member of
the Kidney Health Australia (KHA) Advisory Committee and
Chronic Kidney Disease Surveillance Group.
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