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Kidney Int. 2012 February ; 81(3): 247–255. doi:10.1038/ki.2011.358.

A practical approach to the treatment of depression in patients

with chronic kidney disease and end-stage renal disease
S. Susan Hedayati1,2, Venkata Yalamanchili2, and Fredric O. Finkelstein3
1Renal Section, Medical Service, Veterans Affairs North Texas Health Care System, Dallas,

Texas, USA
2Divisionof Nephrology, Department of Medicine, University of Texas Southwestern Medical
Center, Dallas, Texas, USA
3Hospital of Saint Raphael, Yale University, Renal Research Institute, New Haven, Connecticut,
USA

Abstract
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Depression is a common, under-recognized, and under-treated problem that is independently

associated with increased morbidity and mortality in CKD patients. However, only a minority of
CKD patients with depression are treated with antidepressant medications or nonpharmacologic
therapy. Reasons for low treatment rates include a lack of properly controlled trials that support or
refute efficacy and safety of various treatment regimens in CKD patients. The aim of this
manuscript is to provide a comprehensive review of studies exploring depression treatment
options in CKD. Observational studies as well as small trials suggest that certain serotonin-
selective reuptake inhibitors may be safe to use in patients with advanced CKD and ESRD. These
studies were limited by small sample sizes, lack of placebo control, and lack of formal assessment
for depression diagnosis. Nonpharmacologic treatments were explored in selected ESRD samples.
The most promising data were reported for frequent hemodialysis and cognitive behavioral
therapy. Alternative proposed therapies include exercise training regimens, treatment of anxiety,
and music therapy. Given the association of depression with cardiovascular events and mortality,
and the excessive rates of cardiovascular death in CKD, it becomes imperative to not only
investigate whether treatment of depression is efficacious, but also whether it would result in a
reduction in morbidity and mortality in this patient population.
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Keywords
antidepressant; chronic kidney disease; depression; dialysis; treatment

Major depressive disorder, defined as a clinical syndrome lasting for 2 weeks during which
time the patient experiences either depressed mood or anhedonia plus at least 5 of the 9
Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) criterion symptom
domains,1,2 is very common among patients with chronic kidney disease (CKD) and end-
stage renal disease (ESRD) and is associated with adverse outcomes.3–9 Whereas depression
point prevalence is 2–10% in the general population,10 20% of CKD patients suffer from a

© 2011 International Society of Nephrology

Correspondence: S. Susan Hedayati, Nephrology Section, Veterans Affairs North Texas Health Care System, MC 111G1, 4500 South
Lancaster Road, Dallas, Texas, USA. susan.hedayati@utsouthwestern.edu.
DISCLOSURE
All the authors declared no competing interests.
 Hedayati et al. Page 2

major depressive episode,11,12 a prevalence even higher than reported for other chronic
diseases such as diabetes mellitus and congestive heart failure.13,14 Depression results in
substantial functional impairment and decreased quality of life in ESRD patients,15–17 and
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levels of depression and functional and occupational impairment do not remit spontaneously
in untreated depressed patients.18 We showed that ESRD patients on chronic hemodialysis
(HD) with depression are twice as likely to die or require hospitalization within a year as
compared with those without depression,4 and are at risk for a 30% increase in both
cumulative hospital days and number of hospitalizations.5 In a recent prospective
observational cohort study of consecutively recruited stage 2–5 CKD predialysis patients, a
diagnosis of current major depressive episode at baseline was associated with an increased
risk of a composite of death, hospitalization, or progression to dialysis, independent of
comorbidities and kidney disease severity (adjusted hazard ratio 1.86, 95% confidence
interval 1.23, 2.84).9 Despite the high prevalence of depressive symptoms as well as
depressive disorder among patients with CKD and ESRD and its association with poor
outcomes, only a minority of chronic dialysis patients receive adequate diagnosis and
treatment for depression.3,12,19 For example, in a retrospective analysis of the African
American Study of Kidney Disease and Hypertension Cohort Study, Fischer et al.20 reported
that only 20% of CKD participants with a Beck Depression Inventory (BDI) score of >14
(above the threshold validated for depression) were prescribed antidepressant medications.
Similarly, Watnick et al.12 reported that only 16% of ESRD patients initiating chronic HD
with BDI scores of ≥15 were on antidepressants. In a prospective observational cohort of 98
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prevalent HD patients, nephrologists were informed about a current diagnosis of depressive

disorder based on DSM IV diagnostic criteria in 26% of cases.4 However, intervention was
made in only 23% of these patients, defined as referral to mental health clinic, initiation of
an antidepressant medication, or increasing the dose of previously prescribed antidepressant.
Thus, a major challenge for clinicians is to develop strategies to better understand and
manage depression in CKD patients. However, there are limited data on safety and efficacy
of antidepressant medications in patients with advanced CKD and ESRD. In addition,
instituting effective treatment programs for depression in this patient population is
challenging.20 Recently, attention has begun to be focused on a variety of treatment
strategies that may show future promise in selected groups of patients. The purpose of the
present manuscript is to review the available evidence on treatment of depression in CKD
patients.

SCREENING FOR AND DIAGNOSIS OF DEPRESSION

Given the high prevalence of depression in CKD patients and the association of depression
with poor outcomes and reduced health-related quality of life, it is suggested that depression
screening be integrated into routine patient care. Screening can take place on initial
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presentation of CKD patients for evaluation in clinic, at dialysis initiation for ESRD
patients, and perhaps 6 months after initiation, and yearly thereafter.3 Several studies
validated commonly used depression screening self-report questionnaires against DSM IV-
based structured interviews among patients with CKD and ESRD.3,11,21,22 Table 1 lists the
screening characteristics of these questionnaires, which can generally be completed in a few
minutes. Any of these validated scales can be used to screen patients in CKD clinic or
dialysis facilities. As seen here, the cutoff scores with the best diagnostic accuracy for
depressive disorder in patients with predialysis stage 2–5 CKD were similar to cutoffs used
in the general population (Table 1).

However, the cutoffs for those with ESRD were generally higher, perhaps because of more
frequent presence of somatic symptoms in ESRD that may not be manifest in earlier CKD
stages.11 Thus, somatic symptoms, such as fatigue, loss of energy, decreased appetite, sleep
disturbance, and difficulty concentrating, suggestive of depressive affect, may be more

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 Hedayati et al. Page 3

commonly reported by ESRD patients.19,23–25 However, for a definitive diagnosis of

depressive disorder based on DSM IV, either feelings of sadness (depressed mood) or loss of
interest (anhedonia) must accompany these symptoms.2 If sadness or anhedonia is absent,
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consideration should be given to other causes such as dialysis inadequacy, poor nutritional
status, cognitive dysfunction, dementia, and/or exacerbation of other comorbid illnesses,
such as congestive heart failure (Figure 1). To help distinguish these symptoms, a structured
interview should be performed to confirm a depressive disorder in patients who screen
positive before treatment is considered. This can be performed by any of several individuals
working in the clinic or dialysis facility (nephrologists or trained social workers and/or
nurses).

Alternatively, referrals can be made to mental health professionals, if clinically indicated;

but this approach may present logistical problems in terms of reimbursement issues and
referral channels. Reasons to prompt referral to mental health include complicated
depression such as with psychosis, clinical suspicion for other psychiatric diseases such as
bipolar disorder, suicidal ideation, or treatment-resistant depression (Figure 1).

Paying attention to the presence of acute suicidal intent in depressed patients is particularly
important in order to rule out immediate threat to themselves or others, and needs to be
integrated into the patient evaluation.
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TREATMENT ALGORITHMS
Once the diagnosis of clinical depression is made, treatment options need to be tailored to
the individual needs of the patient and the resources available to the clinical team or dialysis
facility (Figure 1). Thus, the care of each patient needs to be individually assessed and a
treatment plan developed. There are a variety of treatment options available (discussed
below), but few studies guide us as to the best evidence-based approach. In the following
section, we review the pharmacologic and nonpharmacologic approaches to treating
depression that have been suggested and studied in this patient population.

Pharmacologic intervention
Patients with moderate to advanced CKD and ESRD have generally been excluded from
large antidepressant trials because of concerns for adverse events and the paucity of data on
safety of antidepressants in this population.26 This likely has contributed to the
undertreatment and underdosing of antidepressant medications in CKD patients. In fact, few
studies have critically examined the pharmacologic treatment of depression in CKD patients.

Antidepressant medications are generally highly protein bound and not removed
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significantly by the dialysis procedure.27,28 They commonly undergo hepatic metabolism,

but many have active metabolites that are renally excreted, leading to accumulation of
potentially toxic metabolites in patients with decreased glomerular filtration rates.27,28 In
addition, there is the risk of drug–drug interactions in CKD and ESRD patients who,
because of a large burden of comorbidities and metabolic derangements, are already on
many medications. Several classes of antidepressants such as serotonin modulators,
tricyclics, and tetracyclics have cardiac side effects such as QTc prolongation, arrhythmias,
and orthostatic hypotension (Table 2). Given that a large proportion of patients with CKD
and ESRD suffer from cardiovascular (CV) disease, use of such medications without clinical
trials to advocate safety must be carefully considered. Central nervous system depression is
also a common adverse event. Increased bleeding risk was reported in association with
serotonin-selective reuptake inhibitors (SSRIs),29 which may become problematic in
advanced CKD and underlying platelet dysfunction related to uremia. Finally, the
serotonergic gastrointestinal activity of SSRIs, one of the most commonly used

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antidepressant classes, can result in nausea and vomiting, which again may exacerbate these
symptoms in patients with predialysis stage 5 CKD and ESRD.27,30
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There are insufficient data to clearly suggest that treatment of major depressive disorder is
either efficacious or changes outcomes in advanced CKD and ESRD patients.3,31,32 Few
studies have examined this issue and are fraught with serious limitations including small
sample sizes,33–37 lack of placebo control,32–35,37,38 and lack of DSM IV-based criteria for
major depressive disorder.35,36,38 Nonrandomized observational studies of antidepressant
medications in ESRD patients on chronic peritoneal dialysis reported some improvement in
depressive symptoms;32,33 however, major limitations included the lack of a control group,
selection and refusal bias, and a 50% medication discontinuation rate. A total of 136 patients
with ESRD on chronic peritoneal dialysis who scored ≥11 on the BDI depression
questionnaire were studied.32,33 Only 51% agreed to be further evaluated, and of those, only
72% agreed to have pharmacologic treatment. Finally, merely 23 of 44 (52%) of patients
who agreed with treatment completed a 12-week course of antidepressant medications.
Although a mean decrease in BDI scores from 17.1±6.9 to 8.6±3.2 was reported in
completers, this study does underline the fact that even when ESRD patients were given a
diagnosis of depression and treatment recommended, not all agreed to medical
management.32,33

In another study, Atalay et al.39 reported that treatment with SSRI sertraline at 50 mg per
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day for 12 weeks was associated with a decrease in depressive symptoms in 25 chronic
peritoneal dialysis patients, with BDI scores decreasing from 22.4 to 15.7 (P<0.001). Lack
of a control group and small sample size were major limitations. In addition, mean
posttreatment BDI score was still above the cutoff for depression. Koo et al.37 reported
treatment of 34 dialysis patients with another SSRI, paroxetine, at 10 mg per day for 8
weeks concurrently with psychotherapy. Although the authors reported a statistically
significant decrease in Hamilton Depression Rating Scale scores (from 16.6±7.0 to 15.1±6.6,
P<0.01), the clinical relevance of 1.5 unit decrease in score is unclear. This study also
suffered from the lack of a placebo-control group and short-term follow-up. Finally, a
randomized double-blinded placebo-controlled trial of fluoxetine treatment in 14 chronic
HD patients with major depression revealed a statistically significant improvement in
depression at 4 weeks that was not sustained at 8 weeks.36 No patients discontinued study
drug because of adverse events, all of which were reported as minor. Furthermore, all
patients in the intervention arm had serum plasma concentrations of fluoxetine and
norfluoxetine <250 ng/ml at 8 weeks, similar to reported levels in patients with normal renal
function. Although this study suggests promise for use of SSRIs in HD patients, the short
duration and small sample size did not allow for adequate assessment of adverse effects.
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Given the lack of data in CKD and ESRD patients, one might reflect on the antidepressant
medication data that do exist in non-CKD patients, particularly those with CV disease. The
association of depression with increased morbidity and mortality was also reported in non-
kidney disease patients, especially in patients with CV disease.40,41 The Sertraline
AntiDepressant Heart Attack Randomized Trial (SADHART), a randomized, double-
blinded placebo controlled trial, was conducted to assess the safety and efficacy of SSRI
sertraline treatment in 369 patients with major depressive disorder after acute coronary
syndrome.26 This trial documented efficacy and no evidence of CV harm for sertraline
treatment initiated for an average of 34 days after acute coronary syndrome.26 Importantly,
there were 20% fewer serious adverse CV events in the sertraline-treated group versus the
placebo group, although this trend did not reach statistical significance.26 However, this
study was not powered to assess CV events, and to confirm a 20% reduction in CV risk, a
sample size of 4000 would have been required.

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 Hedayati et al. Page 5

Unfortunately, patients with stage 3b–5 CKD and ESRD, which are precisely the groups at
highest risk for CV morbidity and mortality, were excluded from SADHART because of
safety concerns. The discouraging lack of data calls for large randomized placebo-controlled
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trials where CKD subjects are consecutively recruited and outcomes are blindly assessed.
The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST study)
(http://www.clinicaltrials.gov, clinical trials identifier number NCT00946998) is a double-
blinded placebo-controlled trial presently recruiting participants to investigate whether
treatment of a current major depressive episode with sertraline versus placebo improves
depression severity and overall function and quality of life in patients with stage 3–5
predialysis CKD. Secondary outcomes include safety and tolerability.

Recommendations
Until more data are available for treatment of depression in CKD, nephrologists are left with
the conundrum of adding another medication to the growing list prescribed to patients with
advanced CKD or ESRD, considering nonpharmacologic therapy, or worse yet, dismissing
depressive symptoms as nonspecific symptoms of chronic disease or uremia. However, data
clearly suggest that both depression diagnosis and depressive symptoms independently
prognosticate poor outcomes in these patients. Therefore, such symptoms should not be
ignored.

Based on what data are available, if a trial of medication is considered, SSRIs would likely
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be a prudent choice because of established safety in patients with CV disease (Table 2).
Table 2 lists the most common classes of antidepressant medications with specific drug
examples, suggested dosing in renal impairment, and potential adverse effects. Once
medication is initiated, response to treatment, need for dose adjustment, and the
development of side effects should be monitored closely. This can be easily accomplished in
ESRD patients given repeated encounters with health-care providers during routine
presentation to the HD unit. The medication dose should not be escalated sooner than at
intervals of at least 1 to 2 weeks, and only as tolerated. Special attention should be given to
drug–drug interactions, as well as increased risk of suicidal ideation after initiation of
antidepressant medications.

NONPHARMACOLOGIC INTERVENTIONS
Given the concerns and potential problems with pharmacologic treatment of depression in
patients with advanced CKD and ESRD, potential nonpharmacologic interventions have
been considered (Figure 1). These approaches, however, are likely to challenge health-care
providers given the organization and structure of CKD and ESRD care in most countries
(that is, the limited resources available for and limited recognition of the significance of
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providing psychosocial support). Importantly, several studies have now suggested an

improvement in depressive symptoms in ESRD patients treated with various
nonpharmacologic regimens, including alterations in the dialysis treatment regimen,42,43
exercise therapy,44,45 and cognitive behavioral therapy.46 In addition, consideration needs to
be given to alternative approaches that have been used to treat depressed patients in the
general population but which have not been systematically studied in CKD patients.47–49

Alterations in the dialysis treatment

Two recent trials have focused attention on the impact of alterations in the dialysis treatment
regimen on depressive symptoms in HD patients.42,43 These studies lend support to previous
work that observed a beneficial impact of more frequent HD on various health-related
quality-of-life measures.50–52 First, the FREEDOM (Following Rehabilitation, Economics
and Everyday-Dialysis Outcome Measurements) study is an observational cohort study of

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 Hedayati et al. Page 6

patients changing to six times per week HD with the NxStage machine with targeted
standardized weekly KT/V of a minimum of 2.1.53 In all, 239 participants were enrolled
(intention-to-treat cohort), but only 128 completed the study (per-protocol cohort). After
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conversion to six times per week HD, BDI scores decreased from baseline values of
11.2±0.8 to 7.4±0.6 at 4 months, and this improvement was sustained at 12 months (7.8±0.7;
P<0.001), in the per-protocol analysis.42 The greatest improvement in depressive symptoms
was noted in those with the highest baseline BDI scores, and those with scores ≥16 had a
decrease in scores from 25±1 to 14.1±0.9 (P<0.001).42 However, the intention-to-treat
analysis revealed less robust results, and BDI scores decreased from 12.8 to 10.7 (P<0.001).
One criticism of this study was that percent prescribed antidepressant and anxiolytic
medications also increased during the course of the study from 26 to 35% (P = 0.02).
However, after adjustment for antidepressant use, the improvement in BDI scores remained
statistically significant. Given the lack of a control group, the improvement in BDI scores
may have occurred for reasons other than the intervention alone.

The Frequent Hemodialysis Network (FHN) is a 12-month randomized trial comparing six
times per week in-center HD with three times per week conventional HD.43 Standardized
KT/Vs in the former group were 3.54±0.56 compared with 2.49±0.27 in the latter group.
Significant improvements in the physical health composite score of the Short Form-36
(SF-36) health-related quality-of-life questionnaire were observed. BDI scores were lower in
the six times per week HD patients, but the difference was not statistically significant.43
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Cognitive behavioral therapy

Cognitive behavioral therapy (CBT) is a well-documented treatment option for patients with
various psychiatric disorders.54 It is based on the premise that poor decisions, ineffective
problem solving, and distorted or emotional thinking can result from ‘automatic thoughts’ in
response to strong negative feelings and/or emotions. CBT uses well-structured techniques
to support logical thinking and reorganize negative thoughts, behavior adjustments, and
consequently mood status. In a recent 9-month randomized trial of CBT in Brazil, 85 HD
patients with a major depressive disorder on standardized interviewing were randomized to
receive standard care (control group) or CBT with a trained psychologist.46 Group sessions
were held weekly for 12 weeks, and then monthly maintenance sessions were continued.46
Baseline BDI scores decreased from ~25 in both groups to 10.8±8.8 in the treatment group
versus 17.6±11.2 in the control group (between-group comparison P<0.002) at 9 months.
These significant improvements in depressive symptoms in the treatment group were
confirmed with standardized patient interviews. Several domains on the KDQOL-SF
(Kidney Disease Quality of Life questionnaire-Short Form) improved as well.

The benefit of CBT on a broader scale was observed in an interesting study of 69 ESRD
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patients in 22 dialysis units in Louisiana after hurricane-related trauma.55 Social workers

were provided with training kits from the National Kidney Foundation using a cognitive
behavioral framework. There was a significant amelioration of depressive symptoms in
patients who participated in sessions as compared with patients who did not discuss the
material with their social worker. Importantly, this study involved 22 social workers with
limited but focused training, suggesting that more widespread use of CBT techniques may
be promising in ESRD facilities and/or CKD clinics.56

The possible efficacy of combining antidepressant medications with CBT in CKD patients
has not been explored in published studies.57 This is relevant as a large recent study
involving 681 patients with chronic major depression showed that the response rate to
medication or CBT alone was 48%, compared with a 73% response rate in patients receiving
combined therapy.57 It would seem reasonable to explore trials involving combined
approaches given the challenges presented in treating the CKD patient with depression.

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Exercise training programs

The impaired physical functioning of ESRD patients is well documented, the causes of
which are multifactorial.58 An association between physical functioning impairments and
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various health-related quality-of-life measures has been well established.59 Thus, recent
studies suggesting a beneficial effect of exercise programs on depressive symptoms in
ESRD are of interest.44,45 A randomized 2 × 2 factorial trial of anabolic steroid
administration and resistance exercise training was conducted in 79 maintenance HD
patients.60 Interventions included double-blinded weekly nandrolone decanoate or placebo
injections and lower extremity resistance exercise training for 12 weeks during HD using
ankle weights. Exercise was associated with an improvement in self-reported physical
functioning on the Physical Functioning scale of the SF-36 (P = 0.03). In addition, there was
a trend toward a reduction in fatigue in the groups that were assigned to exercise (P = 0.06).
In another trial of HD patients with reduced aerobic capacity (measured as VO2 max
(volume per time, oxygen, maximum)), 35 patients were randomized to a 10-month
intradialytic exercise training program.44 There was a 21% increase in VO2 max in the
exercise group and a 39% reduction in BDI scores—significantly different than in the
control group, in whom there was no change in either exercise capacity or BDI scores.44
Finally, BDI scores decreased by 34.5% (P<0.001) in 24 HD patients randomized to a 1-
year intradialytic exercise training program versus 20 patients randomized to control
group.61 There was an inverse correlation between BDI scores and heart rate variability
indices before and after exercise training, suggesting that decreased heart rate variability
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may play a mechanistic role in the association of depression with poor CV outcomes.

OTHER POTENTIAL APPROACHES AND FUTURE DIRECTIONS

Among symptoms in ESRD patients, pain, sexual dysfunction, and anxiety are commonly
encountered. A total of 44% of prevalent chronic HD patients were observed to have an
anxiety disorder, and in 33% of those, the anxiety disorder persisted at 16 months.62 A
strong association between anxiety and depressive symptoms was noted.62 Given this
association, could the treatment of anxiety improve depressive symptoms in selected
patients? The SMILE study (Symptom Management Involving End-Stage Renal Disease) is
a multicenter, randomized trial comparing the effectiveness of two strategies (provider based
vs. management intervention based) for treatment of symptoms in chronic HD patients.63
The primary outcome includes changes in scores on pain, erectile dysfunction, and
depression scales.

Alternative interventions to treat depression in ESRD patients include addressing marital

and family discord and barriers to social interactions. Marital and family tensions in ESRD
patients are well documented, related at least in part to the stress of illness.64,55 These
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tensions have been associated with the presence of a depressive affect.64 Problems with
social interactions of ESRD patients are also well documented and have been associated
with poor outcomes.65 Involvement of community and religious organizations could be
explored.65–67 Addressing the concerns of caregivers of patients with disabilities may also
be helpful in relieving stress in difficult relationships.68

Other approaches used in non-ESRD samples to treat depression can be considered. A recent
Cochrane analysis suggested that music therapy can have a beneficial impact on depressive
symptoms.47 Importantly, patient acceptance of the therapy was high and dropout was low
in all five studies critically examined. Furthermore, music therapy was shown to be
beneficial in patients with a variety of chronic, advanced illnesses.48 Music and art therapy
can take advantage, perhaps, of the length of time dialysis patients stay idle during the
dialysis treatment.

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Future directions could include exploring the possible association of depression with
inflammation in CKD patients. Data suggest that the reduction in cytokine activation
associated with inflammatory conditions alone without the concomitant administration of
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antidepressant medications can result in amelioration of depressive symptoms. For example,

in 618 patients with psoriatic arthritis treated with etanercept, there was marked
improvement in depressive symptoms, independent of an improvement in associated skin or
joint problems.69

CONCLUSIONS
Patients with CKD suffer from a disproportionate burden of CV morbidity and mortality
both before and after chronic dialysis initiation. However, interventions aimed at modifying
risk factors associated with poor outcomes in these patients have not always translated into
improved outcomes.70–73 In fact, some interventions, such as the use of erythropoiesis-
stimulating agents in the TREAT trial, were associated with harm.73 Yet, as nephrologists,
we spend hours during dialysis rounds in an attempt to fine-tune measures of anemia,
dialysis adequacy, mineral metabolism, and dyslipidemia. Depression has now become a
public health priority, and the US Preventive Services Task Force recommends screening for
depression if systems are in place to assure accurate diagnosis and effective treatment.9,74 It,
therefore, becomes important to institute strategies to screen for and diagnose depression in
CKD patients. What needs to be determined is whether or not treatments are efficacious and
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safe in this patient population, and then effective treatment algorithms need to be
implemented. Importantly, the impact of treating depression on morbidity and mortality
needs to be established. But, it must be emphasized that the successful amelioration of
clinical depression and its symptoms may in and of itself be a valid therapeutic goal.

Acknowledgments
The views expressed here are those of the authors and do not necessarily represent the views of the Department of
Veterans Affairs. This work was supported by VA MERIT grant CX000217-01 and NIH grant
1R01DK085512-01A1 awarded to Dr Hedayati. Support was also provided by the University of Texas
Southwestern Medical Center O’Brien Kidney Research Core Center (P30DK079328).

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Figure 1. Proposed algorithm for management of depression in patients with CKD and ESRD
Alternative therapies include psychotherapy, counseling, social support, and music therapy.
CKD, chronic kidney disease; ESRD, end-stage renal disease; MDE, major depressive
episode.
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Table 1
Screening characteristics of self-report depression scales in CKD and ESRD

Scale No. of items Score, range Cutoff score in general population Cutoff score in CKD (sensitivity, specificity) Cutoff score in ESRD (sensitivity, specificity)

BDI3,11,21,22 21 0–63 ≥10 ≥11 (89%, 88%) ≥14–16 (62–91%, 81–86%)

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QIDS-SR11 16 0–27 ≥10 ≥10 (91%, 88%)

CESD3 20 0–60 ≥16 ≥18 (69%, 83%)

PHQ21 9 0–27 ≥10 ≥10 (92%, 92%)

Abbreviations: BDI, Beck Depression Inventory; CESD, Center for Epidemiologic Studies Depression Scale; CKD, chronic kidney disease; ESRD, end-stage renal disease; PHQ, Patient Health
Questionnaire; QIDS-SR, 16-Item Quick Inventory of Depressive Symptomatology Self-Report.

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Table 2
Antidepressant medication classes and dosing in CKD
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Medication class and dosing in normal eGFR Dosing in CKD and ESRD Potential class adverse effects32

Selective serotonin reuptake inhibitors

Sertraline 50–200 mg/day, single dose No dose adjustment recommended, but active Increased risk of bleeding; GI
metabolite is renally excreted symptoms including nausea and
diarrhea; CNS effects; sexual
dysfunction; hyponatremia
Paroxetine
Immediate-release 20–50 mg/day, single dose Elimination half-life prolonged if CrCl <30
ml/min
Controlled-release 25–62.5 mg/day, single dose Immediate-release: 10 mg/day initial dose,
max 40 mg/day
Controlled-release: 12.5 mg/day initial dose,
max 50 mg/day
Fluoxetine 20–80 mg/day, single dose No dose adjustment recommended, but long
half-life; use with caution
Citalopram 20–40 mg/day, single dose Initial dose 10 mg/day; active metabolite. Higher citalopram doses associated
Not recommended for eGFR <20 ml/min with QTc prolongation, torsades de
pointes
Escitalopram 10–20 mg/day, single dose Use with caution in severe renal impairment
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Dopamine/norepinephrine reuptake inhibitors

Bupropion 200 mg/day, 2 divided doses Active metabolite; reduce frequency and/or Accumulation of toxic metabolites;
dose cardiac dysrhythmia; wide QRS
complex; nausea, insomnia, dizziness
Max 450 mg/day, 3–4 divided doses
Noradrenergic and serotonergic agonist
Mirtazapine 15–45 mg/day at bedtime Reduce dose; clearance reduced by 30% if CNS effects including somnolence;
CrCl 11–39 ml/min, and by 50% if CrCl <10 weight gain
Tricyclics and tetracyclics (TCAs)
Amitriptyline 75–150 mg/day, 1–3 divided Generally avoid TCAs given cardiac side QTc prolongation, arrhythmias,
doses effects orthostatic hypotension; CNS and
No dosage adjustment recommended anticholinergic effects
Desipramine 100–300 mg/day, singly or Caution advised if eGFR <15 ml/min; avoid
divided given cardiac side effects
Doxepin 25–300 mg/day, singly or divided No dosage adjustment recommended
Nortriptyline 25 mg/day, 3 to 4 times daily No dosage adjustment recommended
Max 150 mg/day
Serotonin/norepinephrine reuptake inhibitors
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Venlafaxine
Immediate-release 75–225 mg/day, 2–3 divided Reduce dose by 25 to 50% in patients with Hypertension, sexual dysfunction,
mild-to-moderate renal impairment neuroleptic malignant syndrome,
serotonin syndrome, accumulation of
toxic metabolite O-
desmethylvenlafaxine
Extended-release 37.5–225 mg/day, singly
Serotonin modulators
Nefazodone 100–600 mg/day, 2 divided doses Generally avoid in cardiovascular or liver Cardiac dysrhythmias, Stevens–
disease Johnson syndrome, liver failure,
Increase dose carefully serotonin syndrome, priapism
Trazodone

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Medication class and dosing in normal eGFR Dosing in CKD and ESRD Potential class adverse effects32

Immediate-release 150–400 mg/day, divided Increase dose carefully; use divided doses in
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elderly
Extended-release 150–375 mg/day, singly at night
Monoamine oxidase inhibitors (MAOIs)
Phenelzine 45–90 mg/day, 3 divided doses Avoid MAOI in CKD because of drug–drug Significant drug–drug interactions; risk
interactions, although no dose adjustment of hypertensive crisis with tyramine-
advised for mild-to-moderate renal impairment rich foods; orthostatic hypotension
Selegiline transdermal patch, 6 mg per 24 h,
may increase every 2 weeks by 3 mg per 24 h up
to 12 mg per 24 h

Abbreviations: CKD, chronic kidney disease; CNS, central nervous system; CrCl, creatinine clearance; eGFR, estimated glomerular filtration rate;
ESRD, end-stage renal disease; GI, gastrointestinal.

Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major
depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants
compared with placebo in adults beyond age 24 years, and there was a reduction in risk with antidepressants compared with placebo in adults aged
≥65 years.27
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