

January 2020

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Evidence Synthesis Program (ESP) Center

Portland VA Health Care System

Portland, OR 

Devan Kansagara, MD, MCR, Director 

End-stage Renal Disease and 

Depression: A Systematic Review 



Authors: 

Principal Investigator: 

Karli Kondo, PhD 

Co-Investigators: 

Chelsea Ayers, MPH

Pavan Chopra, MD 

Jennifer Antick, PhD 

Devan Kansagara, MD, MCR

Evidence Synthesis Program
ESRD and Depression Evidence Synthesis Program

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PREFACE

The VA Evidence Synthesis Program (ESP) was established in 2007 to provide timely and 

accurate syntheses of targeted healthcare topics of importance to clinicians, managers, and 

policymakers as they work to improve the health and healthcare of Veterans. These reports help: 

• Develop clinical policies informed by evidence;

• Implement effective services to improve patient outcomes and to support VA clinical 

practice guidelines and performance measures; and 

• Set the direction for future research to address gaps in clinical knowledge.

The program is comprised of four ESP Centers across the US and a Coordinating Center located 

in Portland, Oregon. Center Directors are VA clinicians and recognized leaders in the field of 

evidence synthesis with close ties to the AHRQ Evidence-based Practice Center Program and 

Cochrane Collaboration. The Coordinating Center was created to manage program operations, 

ensure methodological consistency and quality of products, and interface with stakeholders. To 

ensure responsiveness to the needs of decision-makers, the program is governed by a Steering 

Committee comprised of health system leadership and researchers. The program solicits 

nominations for review topics several times a year via the program website. 

Comments on this evidence report are welcome and can be sent to Nicole Floyd, Deputy 

Director, ESP Coordinating Center at Nicole.Floyd@va.gov.

Recommended citation: Kondo K, Ayers CK, Chopra P, Antick J, Kansagara D. End Stage 

Renal Disease and Depression: A Systematic Review. Washington, DC: Evidence Synthesis 

Program, Health Services Research and Development Service, Office of Research and 

Development, Department of Veterans Affairs. VA ESP Project #05-225; 2020. Available at: 

https://www.hsrd.research.va.gov/publications/esp/reports.cfm. 

This report is based on research conducted by the Evidence Synthesis Program (ESP) Center located at 

the VA Portland Healthcare System, Portland, OR, funded by the Department of Veterans Affairs, Veterans 

Health Administration, Health Services Research and Development. The findings and conclusions in this 

document are those of the author(s) who are responsible for its contents; the findings and conclusions do 

not necessarily represent the views of the Department of Veterans Affairs or the United States government. 

Therefore, no statement in this article should be construed as an official position of the Department of 

Veterans Affairs. No investigators have any affiliations or financial involvement (eg, employment, 

consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or 

pending, or royalties) that conflict with material presented in the report.
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ACKNOWLEDGMENTS 

This topic was developed in response to a nomination by the VHA Kidney Disease and Dialysis 

Program office and the VHA Dialysis Dashboard committee for an evidence review on screening 

and treatment of depression in end-stage renal disease (ESRD) patients. The scope was further 

developed with input from the topic nominators (ie, Operational Partners), the ESP Coordinating 

Center, the review team, and the technical expert panel (TEP).

In designing the study questions and methodology at the outset of this report, the ESP consulted 

several technical and content experts. Broad expertise and perspectives were sought. Divergent 

and conflicting opinions are common and perceived as healthy scientific discourse that results in 

a thoughtful, relevant systematic review. Therefore, in the end, study questions, design,

methodologic approaches, and/or conclusions do not necessarily represent the views of 

individual technical and content experts. 

The authors gratefully acknowledge Robin Paynter, MLIS, and the following individuals for 

their contributions to this project: 

Operational Partners

Operational partners are system-level stakeholders who have requested the report to inform 

decision-making. They recommend Technical Expert Panel (TEP) participants; assure VA 

relevance; help develop and approve final project scope and timeframe for completion; provide 

feedback on draft report; and provide consultation on strategies for dissemination of the report to 

field and relevant groups.

Susan Crowley, MD, FASN

National Program Director for Kidney Disease and Dialysis

Chief, Renal Section 

VA Connecticut Healthcare System

Andrew S. Pomerantz, MD

National Mental Health Director, Integrated Services Office of Mental Health and Suicide 

Prevention 

Veterans Health Administration, Washington, DC

Edward P. Post, MD, PhD

National Primary Care Director, Primary Care-Mental Health Integration with the Office of 

Primary Care

Veterans Health Administration, Washington, DC

Laura D. Taylor, LSCSW

National Director, Social Work, Veterans Health Administration; Care Management, Chaplain, 

and Social Work.

Veterans Health Administration, Washington, DC
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Technical Expert Panel (TEP)

To ensure robust, scientifically relevant work, the TEP guides topic refinement; provides input 

on key questions and eligibility criteria, advising on substantive issues or possibly overlooked 

areas of research; assures VA relevance; and provides feedback on work in progress. TEP 

members are listed below:

Michael Fischer, MD, MSPH

Jesse Brown VA Medical Center

Chicago, IL

Steven Weisbord, MD, MSc

VA Pittsburgh Healthcare System

Pittsburgh, PA

Suzanne Watnick, MD

Northwest Kidney Centers

Seattle, WA

Peer Reviewers

The Coordinating Center sought input from external peer reviewers to review the draft report and 

provide feedback on the objectives, scope, methods used, perception of bias, and omitted 

evidence. Peer reviewers must disclose any relevant financial or non-financial conflicts of 

interest. Because of their unique clinical or content expertise, individuals with potential conflicts 

may be retained. The Coordinating Center and the ESP Center work to balance, manage, or 

mitigate any potential nonfinancial conflicts of interest identified.
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TABLE OF CONTENTS

Acknowledgments ......................................................................................................................... ii

Abstract .......................................................................................................................................... 1

Executive Summary ...................................................................................................................... 2

Aim ............................................................................................................................................. 2

Methods ...................................................................................................................................... 2

Results ......................................................................................................................................... 2

Table i. Positive and negative predictive values associated with depression rates in 4 US 

populations .................................................................................................................................. 3

Table ii. Strength of evidence of intervention effectiveness ...................................................... 5

Conclusion .................................................................................................................................. 6

Abbreviations Table .................................................................................................................... 7

Evidence Report .......................................................................................................................... 10

Introduction ................................................................................................................................. 10

Methods ........................................................................................................................................ 12

Topic Development ................................................................................................................... 12

Search Strategy ......................................................................................................................... 13

Study Selection ......................................................................................................................... 13

Data Abstraction ....................................................................................................................... 18

Quality Assessment ................................................................................................................... 18

Data Synthesis ........................................................................................................................... 18

Rating the Body of Evidence .................................................................................................... 18

Results .......................................................................................................................................... 20

Key Question 1: What are the performance characteristics of screening tools for depression in 

patients with ESRD? ................................................................................................................. 22

Diagnostic Accuracy Studies: A Primer ................................................................................... 35

Summary of Findings ............................................................................................................ 35

Ongoing studies .................................................................................................................... 40

Key Question 2: What is the impact of screening for depression in patients with ESRD on 

intermediate and/or patient outcomes? ..................................................................................... 40

Key Question 3. What is the effectiveness of depression treatment in patients with ESRD and 

depression? ................................................................................................................................ 40
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Summary of findings ............................................................................................................. 40

Ongoing studies .................................................................................................................... 43

Key Question 4: In patients with ESRD and depression, what are the potential harms of 

screening and treatment? .......................................................................................................... 67

A. Screening....................................................................................................................... 67

B. Treatment ...................................................................................................................... 67

Key Question 5: Do the benefits or harms of screening differ by subpopulation? ................... 68

Key Question 6: Do the benefits or harms of treatment differ by subpopulation? ................... 68

Patient Characteristics ........................................................................................................... 68

Timing and Type of Follow-up ............................................................................................. 68

Discussion..................................................................................................................................... 69

Limitations ................................................................................................................................ 73

Research Gaps/Future Research ............................................................................................... 73

Implications for the VHA ......................................................................................................... 74

Conclusion ................................................................................................................................ 74

References .................................................................................................................................... 75

Tables

Table 1. PICOTS by Key Question .......................................................................................... 15

Table 2. Characteristics of studies examining the diagnostic accuracy of depression screening 

tools in patients with ESRD (KQ1) .......................................................................................... 24

Table 3. Findings of studies examining the diagnostic accuracy of depression screening tools 

in patients with ESRD ............................................................................................................... 32

Table 4. Beck Depression Inventory-II (BDI-II) characteristics by threshold among studies 

screening for Major Depressive Disorder (MDD) .................................................................... 36

Table 5. Beck Depression Inventory-II (BDI-II) characteristics by threshold among studies 

screening for Major Depressive Disorder (MDD) and less severe depression ......................... 36

Table 6. Studies comparing a depression tool to another validated depression tool ................ 39

Table 7. Characteristics of randomized controlled trials of interventions for depression in 

ESRD outpatients ...................................................................................................................... 44

Table 8. Efficacy of interventions for depression in ESRD patients from randomized 

controlled trials ......................................................................................................................... 52

Table 9. Summary of the evidence on interventions for depression in patients with ESRD .... 63

Table 10. Ongoing randomized controlled trials of depression treatments in patients with 

ESRD ........................................................................................................................................ 66
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Table 11. Positive and negative predictive values associated with depression rates in 4 US 

populations ................................................................................................................................ 70

Table 12. Strength of evidence of intervention effectiveness ................................................... 72

Figures

Figure 1. Analytic Framework .................................................................................................. 13

Figure 2. Literature Flow Chart ................................................................................................ 21

Figure 3. Risk of Bias of Diagnostic Accuracy Studies ........................................................... 23

Appendix A. Search Strategies .................................................................................................. 81

Appendix B. Study Selection ...................................................................................................... 91

Appendix C. Quality and applicability assessment of diagnostic studies .............................. 93

Appendix D. Quality and applicability assessment of randomized controlled trials ............ 95

Appendix E. Adverse events reported in depression treatment trials in patients with endstage renal disease ....................................................................................................................... 97

Appendix F. Peer Review Comments/Author Responses ........................................................ 99
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ABSTRACT

Aim: We conducted a systematic review to evaluate the performance characteristics of screening 

tools for depression in Veterans with end-stage renal disease (ESRD), and to better understand 

the impact, benefits, and harms of depression screening and subsequent treatment for depression.

Methods: We searched electronic databases, clinical trial registries, and reference lists through 

April 2019 for diagnostic accuracy studies of depression tools for patients with ESRD and for 

trials examining the effectiveness of interventions for the treatment of depression in patients with 

ESRD. We abstracted data on study design, interventions, and outcomes. Dual assessment of a

study’s full text, quality, and strength of evidence (SOE) was agreed upon by consensus using 

pre-specified criteria. 

Results: We included 20 treatment RCTs and 16 diagnostic accuracy studies. The best-studied 

tool was the Beck Depression Inventory-II (BDI-II). Across 4 BDI-II studies, a cutoff of ≥16 

provides the best balance between sensitivity and specificity. The BDI-II performed reasonably 

well when compared to a gold standard clinical interview.

SSRIs were the most studied type of drug and the evidence was largely insufficient. We found 

moderate SOE that long-term, high-dose Vitamin D3 is ineffective for reducing depression 

severity. Cognitive behavioral therapy (CBT) is more effective than (undefined) psychotherapy 

and placebo for depression improvement and quality of life (low SOE), and acupressure is more 

effective than treatment as usual (TAU) or sham to reduce depression severity (low SOE).

Conclusion: There is limited research evaluating the diagnostic accuracy of most screening tools 

for depression in patients with ESRD. The BDI-II with a cutoff of ≥16 provides a good balance 

of sensitivity and specificity. More research is needed to support the use of other tools. We found 

low SOE that CBT, sertraline, and acupressure may be beneficial. There is moderate SOE that 

high-dose Vitamin D3 is ineffective. More research is needed.
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EXECUTIVE SUMMARY

AIM

We conducted a systematic review to evaluate the performance characteristics of screening tools

for depression in Veterans with end-stage renal disease (ESRD), and to better understand the 

impact, benefits, and harms of depression screening and subsequent treatment for depression.

METHODS

We conducted a systematic review by searching electronic databases, clinical trial registries, and 

reference lists from database inception through April 2019 for diagnostic accuracy studies of 

depression tools for patients with ESRD and for randomized and non-randomized controlled 

trials directly comparing pharmacological and non-pharmacological interventions for depression 

in ESRD patients to each other, placebo, or waitlist control. We abstracted data on study design, 

interventions, and outcomes. Dual assessment of studies’ full text, quality, and strength of 

evidence (SOE) was agreed upon by consensus using pre-specified criteria. 

RESULTS

We included 20 treatment randomized controlled trials (RCT)s and 16 diagnostic accuracy 

studies.

Key Question 1. What are the performance characteristics of screening tools for 

depression in patients with ESRD?

For diagnostic accuracy, the best studied tool was the Beck Depression Inventory-II (BDI-II). 

Table i uses data from the 2 United States (US) and 2 United Kingdom (UK) studies that 

screened for major depressive disorder (MDD) to compare positive and negative predictive 

values across reported MDD prevalence rates for a) the general US population (7.1%); b) 

Veterans receiving care in Veterans Health Administration (VHA) patient-centered medical 

homes (13.5%); c) patients with ESRD, diagnosed using a gold standard clinical interview 

(22.8%); d) Veterans with ESRD (method of diagnosis not-reported; 33%), and e) patients with 

ESRD, diagnosed using a screening tool (39.3%). Studies evaluate both the BDI-II and the 

Patient Health Questionnaire-9 (PHQ-9) and highlight the impact of the population-specific 

prevalence rate on positive and negative predictive values for a specific threshold. It is important 

to note that at the higher prevalence rates seen in patients with ESRD, negative predictive value 

is generally high. However, positive predictive value is often less than ideal (due to the higher 

rate of false positives), and providers should keep this in mind if using the results of depression 

screening tools to guide treatment decisions.

Across the 4 BDI-II studies, a cutoff of ≥16 provides the best balance between sensitivity and 

specificity. In fact, we found that in some studies, the BDI-II performed reasonably well when 

compared to a gold standard clinical interview. The caveats, however, are that very few studies 

included participants that resemble US Veterans, there was heterogeneity across studies in the 

way the tools were administered, and very few studies contributed data for the same thresholds.
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Table i. Positive and negative predictive values associated with depression rates in 4 US

populations

Author, Year

N, % MDD 

(Ref), % MDD 

Tool, Cutoff

Sensitivity 

(%)

Specificity 

(%)

Prevalence 

Assumption 

(%)

Positive 

Predictive 

Value

Negative 

Predictive Value

Beck Depression Inventory-II (BDI-II)

Balogun, 2011

N = 96

30.6%, 37.1%

BDI ≥10

68 77

7.1a 0.88 0.50

13.5b 0.32 0.94

22.8c 0.47 0.89

33.0d 0.59 0.83

39.3e 0.66 0.79

Watnick, 2005

N = 62

19.4%, NR

BDI ≥16

91 86

7.1a 0.33 0.99

13.5b 0.50 0.98

22.8c 0.66 0.97

33.0d 0.76 0.95

39.3e 0.81 0.94

Chilcot, 2008

N = 40

22.5%; 30-

32.5%

BDI ≥16

88.9 87.1

7.1a 0.35 0.99

13.5b 0.52 0.98

22.8c 0.67 0.96

33.0d 0.77 0.94

39.3e 0.82 0.92

Grant, 2008

N = 57

12.3%; 31.6%

BD I≥15 

100 78

7.1a 0.26 1.0

13.5b 0.42 1.0

22.8c 0.57 1.0

33.0d 0.69 1.0

39.3e 0.74 1.0

Patient Health Questionnaire 9 (PHQ-9)

Watnick, 2005

N = 62

19.4%, NR

PHQ-9≥10 

92 92

7.1a 0.47 0.99

13.5b 0.64 0.99

22.8c 0.77 0.97

33.0d 0.85 0.96

39.3e 0.88 0.95 a General US population, b Veterans receiving care in VHA patient-centered medical homes, c Patients with ESRD, 

diagnosed using a gold standard clinical interview, d Veterans with ESRD (diagnosis method NR), e Patients with 

ESRD, diagnosed using a screening tool. Abbreviations: BDI-II = Beck Depression Inventory-II; MDD = Major 

Depressive Disorder

Studies evaluating a (typically short) screening tool against an established validated tool 

performed well overall. Since the Quality Incentive Program (QIP) requires a follow-up 

assessment after an initial positive screen, these short tools may be good options for this purpose. 

The BDI-Fast Screen (FS) in particular performed well when compared to the BDI-II. 
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Key Question 2. What is the impact of screening for depression in patients with 

ESRD on intermediate and/or patient outcomes?

We identified no studies examining the impact of screening on intermediate or health outcomes.

Key Question 3. What is the effectiveness of depression treatment in patients 

with ESRD and depression?

Among pharmacological interventions SSRIs were the most-studied drug class, and the evidence 

was largely insufficient, except for low-strength evidence from 1 trial of sertraline that it 

improves clinician-rated depression more than cognitive behavioral therapy (CBT). We found 

moderate SOE that long-term, high-dose Vitamin D3 is ineffective for reducing depression 

severity. For non-pharmacological treatments we found low SOE that CBT is more effective than 

other forms of psychotherapy and placebo for depression improvement and quality of life. There 

was also low SOE for acupressure reducing depression severity when compared with usual 

treatment or sham acupressure (see Table ii). Evidence on all other treatments was insufficient to 

draw conclusions. 
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Table ii. Strength of evidence of intervention effectiveness 

Note. Colors represent the Strength of Evidence: Gray = Insufficient evidence; yellow = low SOE; blue = moderate

SOE

Abbreviations: CBT = cognitive behavioral therapy; MBSR = mindfulness-based stress reduction; SSRI = selective 

serotonin reuptake inhibitor; TAU = treatment as usual; TEAS = transcutaneous electrical acupoint stimulation. 
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Key Question 4. In patients with ESRD and depression, what are the potential 

harms of screening and treatment?

Five pharmacological trials reported adverse events. In trials of sertraline, withdrawal due to AEs 

and nausea were more frequently in participants who received sertraline versus placebo. 

However, frequency and severity were similar to the general population. Withdrawals due to 

AEs were also reported in a study of high-dose Vitamin D3. 

Key Question 5. Do the benefits or harms of screening differ by subpopulations?

One study compared the BDI-II administered on- versus off-dialysis. Agreement was generally 

high, particularly among depressed participants. However, among non-depressed participants, 

somatic symptom scores and overall BDI-II scores were higher when assessed on dialysis.

Key Question 6. Do the benefits or harms of treatment differ by subpopulations?

Three trials examined differences in the benefits or harms of interventions for the treatment of

depression in patients with ESRD by subpopulation. Findings suggest no difference in the effect 

of high-dose Vitamin D3 or omega-3 fatty acids by demographic characteristics. Participants

with vascular depression receiving high-dose Vitamin D3 reported significantly greater symptom 

reduction than those with MDD. Finally, among participants receiving CBT, symptom reduction 

was greater for those who received the intervention immediately versus the waitlist control. 

CONCLUSION

There is limited research evaluating the diagnostic accuracy of most screening tools for 

depression in patients with ESRD, and the existing studies may not be generalizable to patients 

in the US and Veterans receiving care in VHA settings. Screening and intervention studies suffer 

from limitations related to methodological quality or reporting. In adults with ESRD, the BDI-II 

with a cutoff of ≥16 provides a good balance of sensitivity and specificity. More research is 

needed to support the use of other tools. We found low-strength evidence that sertraline and CBT 

provide benefit for depressive symptoms, and do not differ significantly from each other. There 

is low-strength evidence that CBT is more effective than psychotherapy or placebo for 

depressive symptoms and quality of life, low-strength evidence that acupressure is more 

effective for reducing depression than sham or usual care, and moderate-strength evidence that 

high dose vitamin D3 is ineffective. Although our ability to form conclusions about the 

effectiveness of interventions for depression in patients with ESRD is limited, it is important to 

note that across studies within-group improvements were common, despite insignificant 

differences between groups, suggesting that treatment generally may be better than no treatment 

in this population. More research is needed.
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ABBREVIATIONS TABLE

Abbreviation Term

AE Adverse event

AKI Acute kidney injury

BDI Beck Depression Inventory

BDI-II Beck Depression Inventory-II

BDI-FS Beck Depression Inventory-Fast Screen

BP Blood pressure

BRT Benson Relaxation Technique

CA California

CBT Cognitive Behavioral Therapy

CDI Cognitive Depression Index

CDSR Cochrane Database of Systematic Reviews

CES-D Center for Epidemiologic Studies Depression Scale

CI Confidence interval

CKD Chronic Kidney Disease

CMS Centers for Medicare and Medicaid Services

COPD Chronic Obstructive Pulmonary Disease

CVD Cardiovascular disease

DASS Depression, Anxiety, and Stress Scale

DBP Diastolic blood pressure

DI-MHD Depression Inventory – Maintenance Hemodialysis

DM Diabetes Mellitus 

EBM Evidence-based Medicine

ED Emergency department

EPC Evidence-based Practice Center

ESAS Edmonton Symptom Assessment Scale

ESP Evidence Synthesis Program

ESRD End-stage Renal Disease

ET Exercise training

FLU Fluoxetine

GDS-15 Geriatric Depression Scale-15

HADS Hospital Anxiety and Depression Scale

Ham-D Hamilton Depression Rating Scale

HD Hemodialysis

HR Heartrate

HRV Heartrate variability

HS High school

ICD-10 International Statistical Classification of Diseases and Related Health Problems-10

KDQOL-SF 36 Kidney Disease Quality of Life-Short Form 36

KQ Key Question

LPD Latihan Pasrah Diri
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MA Meta-analysis

MADRS Montgomery–Åsberg Depression Rating Scale

MAOI Monoamine oxidase inhibitor

MBSR Mindfulness-based Stress Reduction

MD Mean difference

MDD Major depressive disorder

MHI5 Mental Health Inventory 5

MINI Mini International Neuropsychiatric Interview

MMSE Mini-Mental Status Examination

MX Mexico

NM New Mexico

NR Not reported

NRCT Non-randomized controlled trial

NS Not significant

NY New York

OPCC&CT Office of Patient Centered Care and Cultural Transformation

OR Oregon

P P-value

P4P Pay-for-performance

PBO Placebo

PCP Primary care provider

PD Peritoneal dialysis

PFS Piper Fatigue Scale

PHQ-9 Patient Health Questionnaire-9

PICOTS Population, interventions, comparators, outcomes, timing, setting, and study design

PLC Profile of Quality of Life in the Chronically Ill

PSE Psychoeducation

PSQI Pittsburgh Sleep Quality Index

pts Participants

QIDS-C Quick Inventory of Depressive Symptomatology - Clinician

QIP Quality Incentive Program

QOL Quality of Life

QUADAS Tool for the Quality Assessment of Diagnostic Accuracy Studies

RCT Randomized controlled trial

RR Relative risk

SAE Serious adverse event

SBP Systolic blood pressure

SCID-I The Structured Clinical Interview for DSM-IV Axis I Disorders

SE Standard error

SERT Sertraline

SMD Standard mean difference

SOE Strength of evidence

SR Systematic review
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SRQ Self-Reporting Questionnaire

SSRI Selective serotonin reuptake inhibitor

TAU Treatment as usual

TEAS Transcutaneous Electrical Acupoint Stimulation

TEP Technical expert panel

TX Texas

UK United Kingdom

US United States 

VA Veterans Affairs

VHA Veterans Health Administration

WA Washington
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EVIDENCE REPORT

INTRODUCTION

The incidence and prevalence of end-stage renal disease (ESRD) in the United States (US) have

increased steadily over the past 4 decades.1 Veterans experience a higher burden of chronic 

kidney disease (CKD) and ESRD than the population at large.2 Roughly 13,000 Veterans initiate 

dialysis annually, making up nearly 11% of all cases in the US.2

Patients with ESRD experience major depressive disorder (MDD) at 3 to more than 6 times that 

of the general US population, depending on the method of assessment.3,4 Comorbid depression is 

associated with treatment noncompliance, poorer quality of life, worse sleep, increased

emergency department (ED) visits, hospitalizations, suicide, and all-cause mortality.5-8

Veterans experience MDD at more than twice the rate of the general US population (7.1% vs 

13.5%).3,9 According to United States Renal Data System (USRDS) data, rates of depression in 

Veterans with ESRD increased steadily between 2007 and 2015, with recent data indicating 

prevalence rates of 33%.10

In the Veterans Health Administration (VHA), some Veterans with ESRD receive kidney care 

entirely within the VHA. However, due to space limitations and variation in dialysis care 

available across VHA settings (inpatient, outpatient, or none), a large percentage of Veterans are 

referred to dialysis units in the community. 

The Centers for Medicare and Medicaid Services’ (CMS) inclusion of depression screening for 

ESRD patients as part of their pay-for-performance (P4P) Quality Incentive Program (QIP) 

requires routine depression screening for patients with ESRD.11 However, due to the lack of 

system-wide screening tool requirements, there is wide variation in the tools used to initially 

screen for depression, as well as for follow-up after a positive initial screen (ranging from the 

Patient Health Questionnaire 2 [PHQ-2] to the Center for Epidemiologic Studies Depression 

Scale [CES-D], and the Beck Depression Inventory [BDI-II], to a clinical interview). In addition, 

the implementation of depression screening likely varies widely by site, potentially ranging from 

the PHQ-2 included on written intake forms or verbal assessment in a waiting room, to a 

confidential interview with a licensed clinician. Follow-up to a positive screen also varies 

widely, and Veterans with ESRD and comorbid depression may be referred to mental health 

providers within the VHA, or to community hospitals and mental health settings. 

Currently, there are no established guidelines for the treatment of depression in patients with 

ESRD. Roughly 30% of Veterans receive an antidepressant during the ESRD post-transition 

phase.10 Efficacy studies are limited, however, and the evidence is unclear.12 Psychosocial 

treatments and Cognitive Behavioral Therapy (CBT) are also commonly used; however, 

interventions vary widely, and the evidence is limited.13

Given the wide variation in depression screening and treatment options for Veterans with ESRD, 

an understanding of the validity of screening tools used in both VHA and community settings, 

and the subsequent depression treatment-related outcomes for Veterans in all US healthcare 

settings, is vital.
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The purpose of this review is to identify depression screening tools (and/or thresholds) 

appropriate for Veterans with ESRD, and to better understand the impact, benefits, and harms of 

depression screening and subsequent treatment for depression in Veterans (and Veteran 

subpopulations) with ESRD.
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METHODS

TOPIC DEVELOPMENT

This topic was nominated by Dr. Susan Crowley, VHA National Program Director for Kidney 

Disease and Dialysis. The scope was refined through a process that included a preliminary 

review of published peer-reviewed literature and consultations with our operational partners and 

a technical expert panel (TEP). Our approach was guided by a conceptual framework developed 

in consultation with our operational partners and TEP (Figure 1).

The Key Questions (KQs) for this systematic review were:

KQ1. What are the performance characteristics of screening tools for depression in patients with 

ESRD?

KQ2. What is the impact of screening for depression in patients with ESRD on intermediate 

and/or patient outcomes?

KQ3. What is the effectiveness of depression treatment in patients with ESRD and depression?

a. pharmacological treatment

b. non-pharmacological treatment

c. pharmacological and non-pharmacological treatments combined

KQ4. In patients with ESRD and depression, what are the potential harms of:

a. screening?

b. treatment?

i. pharmacological

ii. non-pharmacological

KQ5. Do the benefits or harms of screening differ by:

a. patient characteristics or other social determinants of health?

b. setting?

c. screening characteristics/process?

d. other (eg, patient engagement/receptivity to treatment, social support)?

e. timing and type of follow up?

KQ6. Do the benefits or harms of treatment differ by:

a. patient characteristics or other social determinants of health?

b. setting?

c. provider characteristics (eg, mental health, primary care provider [PCP], other)?

d. other (eg, patient engagement/receptivity to treatment, social support)?

e. timing and type of follow up?
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Figure 1. Analytic Framework 

Note. Associated key questions are noted in the shaded circles.

SEARCH STRATEGY

Search strategies were developed in consultation with a research librarian and were peer 

reviewed by a second research librarian using the instrument for Peer Review of Search 

Strategies (PRESS).

14 We conducted a review of the literature by systematically searching, 

reviewing, and analyzing the scientific evidence as it pertains to the research questions. To 

identify relevant trials, we searched Ovid MEDLINE, PsycINFO, Elsevier EMBASE, and Ovid 

EBM Reviews Cochrane Database of Systematic Reviews (CDSR, DARE, HTA, Cochrane 

CENTRAL, etc). We searched all available years of publication from database inception (1946 

for Ovid MEDLINE®) through April 2019. We reviewed the bibliographies of relevant articles 

and contacted experts to identify additional studies. To identify in-progress or unpublished 

studies, we searched the VHA HSR&D website, ClinicalTrials.gov, and the World Health 

Organization (WHO) International Clinical Trials Registry Platform (ICTRP). 

STUDY SELECTION

Criteria for population, interventions, comparators, outcomes, timing, and setting (PICOTS) 

were developed in collaboration with our operational partners and TEP (see Table 1). Based on 

pre-specified criteria, 80% of titles and abstracts were reviewed manually by 2 reviewers, and the 

remaining 20% were reviewed by at least 2 reviewers using Abstrackr, a web-based abstract 

screening tool.15 Two reviewers then independently assessed the full text of included citations for 

final inclusion. All discordant results were resolved through consensus or consultation with a 

third reviewer. Articles meeting eligibility criteria were included for data abstraction. 

We included diagnostic accuracy studies of depression tools for patients with ESRD. We also 

included randomized and non-randomized controlled trials, and observational studies of patients 

with ESRD and comorbid depression (defined by established thresholds for chronically ill 

Adults 

with 

ESRD

5

Patient Outcomes: 

• Depressive Dx

• QoL/Functional 

Status

• Hospitalization, 

ED/Urgent care visits

• Mortality

• Suicidal Ideation, 

Attempts

• BP/Metabolic Control

• Employment

Screening

(initial/follow-up)

Referral/Follow-up

(primary care, MH)

5

Mediators/Moderators 

• Patient Characteristics

• Social Determinants 

of Health

• Other

Mediators/Moderators

• Setting, Provider

• Intervention

6

Intermediate

Outcomes: 

• Depressive Sx 

• Med/Treatment

Adherence

• Dialysis 

Adherence

• Reduction in 

Pain meds

Depression 

Diagnosis

1 2

2

Treatment

(timing, type)

2

3

6

7

7
ESRD and Depression Evidence Synthesis Program

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populations)16-20 that directly compared pharmacological and non-pharmacological interventions 

to each other, placebo, or waitlist control. We excluded studies examining patients with acute 

kidney injury (AKI), or with CKD stages 1-4. To examine the impact of screening and 

effectiveness of treatment for depression in patients with ESRD (KQs 2 and 3) we included only 

randomized and non-randomized controlled trials. Citation lists of included systematic reviews 

were reviewed for relevant studies. For each key question of interest, we used a “best evidence” 

approach to guide additional study design criteria depending on the question under consideration 

and the literature available (see Table 1 and Appendix B).

21
ESRD and Depression Evidence Synthesis Program

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Table 1. PICOTS by Key Question 

Key 

Question: 

KQ1: What are 

the 

performance 

characteristic

s of screening 

tools for 

depression in 

patients with 

ESRD? 

KQ2: What is the 

impact of screening 

for depression in 

patients with ESRD on 

intermediate and/or 

patient outcomes?

KQ3: What is the 

effectiveness of 

depression 

treatment in 

patients with ESRD 

and depression:

a. pharmacological?

b. non-pharmacological?

c. pharmacological 

and nonpharmacological 

treatments 

combined 

KQ4: In patients 

with ESRD, what 

are the potential 

harms of:

a. screening? 

b. treatment for 

depressed 

patients? 

i. Pharmacological?

ii. non-pharmacological?

KQ5: Do the benefits or 

harms of screening 

differ by:

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. screening 

characteristics/ 

process? 

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

KQ6: Do the benefits or 

harms of treatment differ 

by: 

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. provider 

characteristics (eg, 

mental health, PCP)?

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

Population Adults with 

ESRD

Adults with ESRD Adults with ESRD and depression (Cutoffs: 

PHQ-9 ≥ 10;16 CES-D ≥ 18;17 HAM-D ≥ 12;18

BDI-II ≥ 16;17,18 BDI ≥ 13;18 HADS ≥ 819,20) 

a. Adults with ESRD

b. Adults with ESRD and 

depression (Cutoffs: 

PHQ-9 ≥ 10;16 CES-D ≥ 

18;17 HAM-D ≥ 12;18 BDIII ≥ 16;17,18 BDI ≥ 13;18

HADS ≥ 819,20)

Adults with ESRD

Intervention Depression screening Pharmacological and 

non-pharmacological 

treatments for 

depression

Depression 

screening, and 

pharmacological and 

non-pharmacological 

treatments for 

depression

Depression screening Pharmacological and nonpharmacological 

treatments for depression

Comparators Clinical 

evaluation, 

Other 

screening 

tools.

Exclude DSMIII and earlier

No screening, other 

screening tool

Placebo, waitlist 

control, other 

intervention

a. No screening, 

other screening 

tool

b. Placebo, waitlist 

control, other 

intervention

No screening, other 

screening tool

Placebo, waitlist control, 

other intervention
ESRD and Depression Evidence Synthesis Program

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Key 

Question: 

KQ1: What are 

the 

performance 

characteristic

s of screening 

tools for 

depression in 

patients with 

ESRD? 

KQ2: What is the 

impact of screening 

for depression in 

patients with ESRD on 

intermediate and/or 

patient outcomes?

KQ3: What is the 

effectiveness of 

depression 

treatment in 

patients with ESRD 

and depression:

a. pharmacological?

b. non-pharmacological?

c. pharmacological 

and nonpharmacological 

treatments 

combined 

KQ4: In patients 

with ESRD, what 

are the potential 

harms of:

a. screening? 

b. treatment for 

depressed 

patients? 

i. Pharmacological?

ii. non-pharmacological?

KQ5: Do the benefits or 

harms of screening 

differ by:

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. screening 

characteristics/ 

process? 

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

KQ6: Do the benefits or 

harms of treatment differ 

by: 

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. provider 

characteristics (eg, 

mental health, PCP)?

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

Outcomes Diagnostic test 

performance:

sensitivity, 

specificity, 

positive 

predictive 

value, and 

negative 

predictive 

value

Therapeutic impact:

timing, setting, or type of 

treatment.

Intermediate and Patient 

outcomes: depressive 

symptoms, mortality, 

suicide attempts or 

completion, 

hospitalization, 

ED/urgent care 

utilization, patient 

satisfaction, adherence 

to dialysis, medication, 

or treatment, pain 

medication reduction, 

BP/metabolic control, 

quality of life, other 

outcomes (eg, 

employment)

Intermediate and 

Patient outcomes:

depressive 

symptoms, mortality, 

suicide attempts or 

completion, 

hospitalization, 

ED/urgent care 

utilization, patient 

satisfaction, 

adherence to dialysis, 

medication, or 

treatment, pain 

medication reduction, 

BP/metabolic control, 

quality of life, other 

outcomes (eg, 

employment)

Adverse effects or 

unintended 

consequences

Intermediate and Patient outcomes: depressive 

symptoms, mortality, suicide attempts or completion, 

hospitalization, ED/urgent care utilization, patient 

satisfaction, adherence to dialysis, medication, or 

treatment, pain medication reduction, BP/metabolic 

control, quality of life, other outcomes (eg, 

employment)

Timing Any

Settings All settings in US or international (VHA, hospital community, community mental health, ED, urgent care, other community)
ESRD and Depression Evidence Synthesis Program

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Key 

Question: 

KQ1: What are 

the 

performance 

characteristic

s of screening 

tools for 

depression in 

patients with 

ESRD? 

KQ2: What is the 

impact of screening 

for depression in 

patients with ESRD on 

intermediate and/or 

patient outcomes?

KQ3: What is the 

effectiveness of 

depression 

treatment in 

patients with ESRD 

and depression:

a. pharmacological?

b. non-pharmacological?

c. pharmacological 

and nonpharmacological 

treatments 

combined 

KQ4: In patients 

with ESRD, what 

are the potential 

harms of:

a. screening? 

b. treatment for 

depressed 

patients? 

i. Pharmacological?

ii. non-pharmacological?

KQ5: Do the benefits or 

harms of screening 

differ by:

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. screening 

characteristics/ 

process? 

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

KQ6: Do the benefits or 

harms of treatment differ 

by: 

a. patient 

characteristics or 

other social 

determinants of 

health? 

b. setting? 

c. provider 

characteristics (eg, 

mental health, PCP)?

d. other (eg, patient 

engagement/ 

receptivity to 

treatment, social 

support)? 

e. timing and type of 

follow up?

Study design Systematic 

reviews, RCTs, 

NRCTs, 

Observational 

studies

Systematic reviews, RCTs, NRCTs Systematic reviews, RCTs, NRCTs, Observational studies

Note. Subpopulations may include: Patient demographic characteristics or social determinants of health; ESRD subgroup (w/o treatment; treated by kidney transplant; treated by 

HD (home or clinic); treated by PD (home or clinic); clinical severity (ESRD or depression); setting (eg VHA, community hospitals, community mental health, ED, urgent care 

visits for mental health, home vs clinic-based dialysis); other.

Abbreviations: CES-D = Center for Epidemiologic Studies Depression Scale; BDI = Beck Depression Inventory; BP = blood pressure; ED = emergency department; ESRD = Endstage Renal Disease; HADS = Hospital Anxiety and Depression Scale; HAM-D = Hamilton Depression Rating Scale; NRCT = Non-randomized controlled trial; PHQ-9 = Patient 

Health Questionnaire-9; RCT = Randomized controlled trial; VHA = Veterans Health Administration
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DATA ABSTRACTION

Data from studies meeting inclusion criteria were abstracted by 1 investigator and confirmed by 

at least 1 additional reviewer. From each study, we abstracted the following where available: 

study design, sample size, setting, population characteristics, subject inclusion and exclusion 

criteria, the study and comparator interventions including details related to the dosage, setting, 

timing, and administration of screening and interventions, duration of treatment, duration of 

follow-up, intermediate and health outcomes, and relevant harms. 

QUALITY ASSESSMENT

Two reviewers independently assessed the methodological quality of each study using 

established methods for each study design. For trials, we used criteria established by the US

Preventive Services Taskforce and adapted for depression interventions.22-24 We supplemented

this with the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies

QUADAS-225 and the Newcastle-Ottawa Scale26 for diagnostic accuracy and observational 

studies respectively (see Appendices C and D). Disagreements were resolved by consensus or a 

third reviewer.

DATA SYNTHESIS

We qualitatively synthesized the evidence for all key questions and presented the findings in 

tables. For Key Question 1, we categorized assessment tools as a) screening for MDD, and b) 

screening for a wider range, from subclinical depressive symptoms to MDD. In addition, we 

present detailed findings for studies comparing a screening tool to a gold standard clinical 

interview, and provide a summary of studies that use another tool as a reference standard (eg, 

BDI-II).27 We were unable to quantitatively synthesize the evidence because studies were not 

clinically heterogenous and/or of the same intervention and outcome measure.

28

RATING THE BODY OF EVIDENCE

We assessed the overall strength of evidence (SOE) for outcomes using a method developed for 

the Agency for Healthcare Research and Quality’s (AHRQ) Evidence-based Practice Centers 

(EPCs).29 The AHRQ EPC method considers study limitations, directness, consistency, 

precision, and reporting bias to classify the strength of evidence for individual outcomes 

independently for randomized controlled trials (RCTs) and observational studies, with 

supplemental domains of dose-response association, plausible confounding that would decrease 

the observed effect, and strength of association, as well as separate guidance for applicability.30

Ratings will be based on the following criteria: 

• High: Very confident that the estimate of effect lies close to the true effect for this 

outcome. The body of evidence has few or no deficiencies, the findings are stable, and 

another study would not change the conclusions.

• Moderate: Moderately confident that the estimate of effect lies close to the true effect for 

this outcome. The body of evidence has some deficiencies and the findings are likely to 

be stable, but some doubt remains. 
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• Low: Limited confidence that the estimate of effect lies close to the true effect for this 

outcome. The body of evidence has major or numerous deficiencies (or both). Additional 

evidence is needed before concluding either that the findings are stable or that the 

estimate of effect is close to the true effect.

• Insufficient: No evidence, unable to estimate an effect, or no confidence in the estimate 

of effect for this outcome. No evidence is available, or the body of evidence has 

unacceptable deficiencies, precluding reaching a conclusion.
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RESULTS

We reviewed a total of 7,452 studies. After title and abstract review, 149 met inclusion criteria. 

Upon full-text review, we included a total of 20 RCTs and 16 diagnostic accuracy studies. RCTs 

examined in Key Questions 4 and 6 were also included in Key Question 3, and the single study 

included for Key Question 5 was also included in Key Question 1 (see Figure 2; quality 

assessment is presented in Appendices C and D).
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Figure 2. Literature Flow Chart 

149 Potentially relevant 

articles for full-text review

113 Excluded publications:

3 No English language publication

55 Excluded population

34 Excluded study design or publication type

15 No comparator of interest

6 Articles unavailable

KQ 1:

16 Studies: 

Diagnostic 

Accuracy

3 Citations identified from reference 

lists of relevant articles and reviews, 

key experts, and other sources

7,455 Citations compiled for 

review of titles and abstracts

36 Total included studies

7,452 Citations identified from electronic database searches*: 

4637 from PubMed/Ovid MEDLINE May 17, 2019

2163 from EMBASE May 16, 2019

325 from PsycINFO May 16, 2019

262 from Ovid EBM Reviews (CDSR, DARE, HTA, Cochrane CENTRAL) May 17, 2019

64 from ClinicalTrials.gov May 16, 2019

1 from WHO ICTRP May 16, 2019

0 from VA HSR&D May 16, 2019

7,306 Titles and abstracts excluded 

for lack of relevance

KQ 6:

3 RCTs

KQ 5:

1 Study: 

Diagnostic 

Accuracy

KQ 4:

11 RCTs

KQ 3:

20 RCTs

KQ 2:

No studies

*after deduplication

Note: studies in KQs 4 & 6 are also included in the KQ3 total, and the KQ5 study is included in KQ1 total
ESRD and Depression Evidence Synthesis Program

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KEY QUESTION 1: What are the performance characteristics of 

screening tools for depression in patients with ESRD?

Sixteen studies examined the performance characteristics for depression screening in patients 

with ESRD. Nine studies examined the performance of the Beck Depression Inventory-II (BDIII).

27 Other tools include the Cognitive Depression Index (CDI31; 4 studies), the Center for 

Epidemiologic Studies – Depression Scale (CES-D32; 1 study33), the Hospital Anxiety and 

Depression Scale - Depressive Subscale (HADS-D34; 2 studies35,36), the Geriatric Depression 

Scale-15 (GDS-1537,38; 2 studies39,40), the Hamilton Depression Rating Scale (Ham-D41; 1 

study42), the Patient Health Questionnaire 9 (PHQ-943; 1 study44), and others. Of note, we 

identified only 1 development and validation study of a depression screening tool targeting 

patients on maintenance dialysis (Depression Inventory – Maintenance Hemodialysis [DIMHD]).45 Table 2 provides study characteristics. 

Five studies33,39,44,46,47 were of US populations, with 2 studies including participants at Veterans 

Health Administration (VHA) facilities.33,44 Other studies were located in Australia,48 Canada,49

China,45 Italy,40 the Netherlands,50,51 Norway,36 Saudi Arabia,52 Turkey,42 and the United 

Kingdom (UK; see Table 2).

50,53

Most studies included only patients undergoing hemodialysis (HD). Only 4 studies also included 

participants undergoing peritoneal dialysis (PD).35,36,44,47 Across studies reporting time on 

dialysis, the minimum number of (mean) months was 8.536 and the maximum was 72.2 (see 

Table 2).

42

Of the 16, 11 studies compared screening tools (index test) to a gold standard clinical interview 

(eg, Structured Clinical Interview for DSM-IV [SCID-I]

54, Mini-International Neuropsychiatric 

Interview [MINI]55), and 5 compared tools to other established, validated assessment measures 

(eg, Beck Depression Inventory [BDI-II]

27, Hospital Anxiety and Depression Scale [HADS]34).

One study compared the BDI-II to a clinical interview, and another tool to the BDI-II.

45 For the 

purpose of this review, we focus primarily on the studies using a clinical interview as a reference 

standard, and summarize the findings of those comparing screening tools to other established 

tools.

Only 5 studies screened participants for MDD specifically.39,44,46,48,52,53 Nine studies screened for 

less severe depressive disorders (eg, dysthymia, pervasive depressive disorder) and/or subclinical 

depressive symptoms in addition to MDD,

35,36,40,42,45,47,49,51,56 and 1 study examined performance 

characteristics and thresholds for both MDD and less severe depression (see Table 2).

50

The 16 studies were relatively similar in quality, with the risk of bias largely unclear for patient 

selection, the index test, and the reference standard. For patient selection, unclear ratings were 

primarily due to the lack of detail related to the sequence of sample enrollment. For the index 

test, few studies reported whether study staff were trained in administration or interpretation of 

the test, and for the reference standard, very few studies reported information related to fidelity.

Risk of bias ratings for timing and flow were low for all but 3 studies, with 1 unclear ROB,

52 and

2 high ROB (see Figure 3 and Appendix C for more detail).39,40
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Figure 3. Risk of Bias of Diagnostic Accuracy Studies

Note. See Appendix C for a description of categories and item list. 
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Table 2. Characteristics of studies examining the diagnostic accuracy of depression screening tools in patients with ESRD (KQ1)

Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

Alsuwaida, 

200652

N = 26

Saudi Arabia

Single Site: hospitalbased outpatient HD 

unit

42% Female

Age: 48.1(15.1)

Education: NR

HD: 100%

Dialysis duration: 

NR

History of 

depression: NR

Inclusion: 18+ years of age, ESRD 

and on maintenance HD for 3+ 

months

Exclusion: Inability to participate in 

psychiatric interview, acute kidney

failure, and delirium. Diagnosed with 

psychiatric disorders other than MDD

SRQ (Arabic Version):

Self-report. Timing: within a 

week of clinical interview

Clinical Interview:

All participants interviewed by the 

same psychiatrist (blinded to 

index test). Timing: up to a week 

before the index test.

SRQ=NR; 15.4%

Balogun, 

201139

N = 96

US

Multisite: dialysis 

units

Of 89 participants:

56% Female

Age: 73.5(6.2)

White: 56.2%

Black: 43.8%

Education: NR

HD: NR

Dialysis duration: 

NR

History of 

depression: NR

Inclusion: 65+ with ESRD treated 

with chronic hemodialysis and able 

to give their informed consent

Exclusion: acute or other chronic 

illness [ie, metabolic (organic) brain 

syndrome, known malignancy, 

dementia], currently using 

antidepressants, and active alcohol 

or recreational drug abuse, did not 

speak English 

BDI, GDS-15:

NR

Clinical Interview:

Geriatric Psychiatrist

Of 62: 

BDI≥10= 37.1%, 

GDS-15 ≥5 = 

32.3%;

30.6%

Bautovich, 

201848

N = 45

Sydney, 

Australia

Single site: 

outpatient dialysis 

unit

42% Female

Age: primarily 65+

Education: NR

HD: 100%

Days on dialysis: M= 

1241(1098)

Included: 18+ years of age, receiving 

HD, adequate English language 

skills 

Excluded: evidence of psychosis, 

drug or alcohol dependence, or 

cognitive dysfunction

BDI, CDI:

Self-report. Timing: before 

clinical interview.

Clinical Interview:

Interviewed by a senior psychiatry 

registrar or psychiatrist, both of 

whom were experienced in 

diagnosing depression amongst 

those with chronic medical illness;

Timing: completed immediately 

after index tests

BDI, CDI = NR; 

13.3%
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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

History of 

depression: NR

Chilcot, 

200853

N = 40 

UK

Multisite: outpatient 

renal service

40% Female

Age: 53.2(14.2)

White: 87.5%

Black Caribbean: 

10%

Asian: 2.5%

Education: NRHD: 

100% (high-flux or 

on-line) 3x/week

Months on dialysis 

M=51.2

History of 

depression: NR

Included: Adult ESRD receiving HD 

for >3 months. 

Excluded: Psychiatric illnesses other 

than MDD, <23 MMSE

BDI, CDI:

Self-report. Completed on 

and off dialysis. On-dialysis 

commenced 30 minutes after 

the start of a stable session. 

Off-dialysis conducted at the 

same as the MINI, 

M=10.7(4.2) days 

before/after.

MINI (ref for BDI): 

Administration by a research 

psychologist who was trained by 

a consultant psychiatrist. Timing: 

10.7(4.2) days before/after the 

on-dialysis BDI, and on the same 

day as the off-dialysis BDI.

BDI-II (ref for CDI):

Self-report. Same day as the CDI.

BDI≥16 on 

dialysis = 32.5%, 

off dialysis = 

30%, CDI≥10 on 

and off dialysis = 

32.5%; 22.5%

1Collister, 

201949

N = 50

Canada

Multisite: outpatient 

HD units

48% Female

Age: 64(12.4)

Education: NR

HD: 100%

3+x/week: 96%

Hours of HD M= 

3.6(0.4)

Dialysis duration: 

NR

History of 

depression: NR

Antidepressants: 

16%

Included: 18+ years of age, receiving 

in-center hemodialysis ≥2x weekly 

for at least the last 90 days

Excluded: unable to complete the 

study instruments due to a cognitive 

impairment or an English language 

barrier

Single question from the 

ESAS:

Self-report scale (0-10) re: 

feeling blue or sad. Timing: 

taken during dialysis during 

the same session as the 

reference test.

HADS:

Self-report. Timing: taken during 

dialysis during the same session 

as the reference test.

ESAS = NR; 

HADS≥7=54%
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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

1Gencoz, 

200742

N = 45

Turkey

Single site: hospitalbased outpatient HD 

unit

42.2% Female

Age: 41.64(11.7)

≤ Middle school: 

37.9%

HD: 100%

Months on HD 

M=72.24(48.48)

History of 

depression: NR

Included: medically stable

with no hospital admission for any 

reason within the last 3 months, and 

maintained on

dialysis for at least 12 months

Excluded: presence of cognitive 

impairment indicated by MMSE 

score lower than 24, presence of a 

history of a psychiatric diagnosis or 

treatment in the last 6 months, and 

presence of some practical 

difficulties like probability of moving 

to another city, blindness or low 

educational level, which may 

decrease the patients’ ability to 

comprehend and/or follow the study 

protocol. Patients who did not 

complete all baseline assessments 

were also excluded from the study.

Ham-D: 

Administered at baseline and 

the following month by a 

clinical psychologist that was 

blind to the reference 

standard. Timing re: 

reference standard: NR

SCID-I (Turkish Translation):

Administered at baseline and the 

following month by a clinical 

psychologist that was blind to the 

reference standard. Timing re: 

index test: NR

Ham-D NR; 4% 

MDD, 18% other 

depressive 

disorders

1Giordano, 

200740

N = 31

Italy

Single site: hospitalbased HD unit

35.5% Female

Age: 70.3(1)

Race: NR

Education: NR

HD: 100%

Dialysis duration: 

NR

History of 

depression: NR

Inclusion: 3+ HD/wk, 65+ years old, 

maintaining functional independence 

or loss of it in only 1 of the 6 basic 

ADL, no evidence of significant 

cognitive impairment per MMSE >24, 

no evidence of severe diseases that 

might highly influence mood state 

(eg, cancer, symptomatic 

cerebrovascular disease with 

residual deficit, schizophrenia and 

other psychoses), and disease 

severity as evaluated by the CIRS 

for overall illness severity for which 

>3 is moderate

Exclusion: Taking antidepressants

GDS-15:

Self-report. Administered by 

a trained interviewer. Timing: 

same session as reference 

standard.

BDI:

Self-report. Administered by a 

trained interviewer. Timing: same 

session as index test.

GDS-15 ≥6 = 

32%; BDI-II ≥14= 

29%
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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

2Grant, 

200850

N = 57

UK

Single site: 

outpatient HD unit

29.8% Female

Age: 62.5(15.8)

Non-White 7%

Education: NR

HD: 100%

Dialysis duration: 

NR 

History of 

depression: NR

Included: 18 and 90 years of age, 

ESRD for 3+ months, receiving HD 

3x/week.

Excluded: Current psychiatric care, 

on medication for a psychiatric 

illness or had seen a psychiatrist for 

follow-up within the last 2 years, 

severe co-morbid illness requiring 

hospitalization. 

BDI:

Self-report. Distributed by a 

healthcare assistant during a 

HD session.

Clinical Interview (based on ICD10 diagnosis):

Interviewed by a trained 

psychologist. Included a full 

psychiatric history and MMSE. 

Timing: within 1 week of index 

test

BDI-II ≥10 = 

56.1%; 12.3%

BDI-II ≥15 = 

31.6%; 

1Hedayati, 

200656

N = 98

US

Durham, NC

March 2003-

April 2004

Multi-site: outpatient 

dialysis units (VA, 2 

non-VA)

44.9% Female

Age: 57.2(13.8)

Veterans: 26.5%

AA/Black: 80.6%

White: 14.3%

Other: 5.1%

≤High school: ≈

44.5% 

HD: 100%

Years on dialysis: 

M=4.1(3.8)

History of 

depression: NR

Included: English-speaking with 

health-care power of attorney and 

could sign consent.

Excluded: NR

BDI, CDI, CESD, Feinstein 

Scale;

RA administered 

BDI/CESD/Feinstein Scale at 

enrollment.

SCID-I: 

Administered by a nephrologist. 

Timing: within 1 week of index 

tests

BDI≥14 = 30.6%, 

CESD ≥18 = 

30.6%; 26.5%

17.3% MDD

1Loosman, 

201035

N = 62

Amsterdam

Feb-June 

2008

Single site: hospitalbased HD and 

outpatient PD

46.8% Female

Age: 63.5(14.9)

64.5% Dutch 

ethnicity

Education: NR

HD: 82%; PD 18%

Included: Patients with ESRD treated 

with HD or PD

Excluded: Patients who were unable 

to read or understand Dutch

BDI, HADS:

Self-report. Completed while 

receiving treatment.

MINI: 

Performed by a medical resident 

who was extensively trained on 

the MINI by a psychiatrist. For 1:7 

patients, MINI interviews were 

performed by both the medical 

resident and the psychiatrist 

(100% Inter-rater reliability). 

Timing: NR

BDI, HADS = 

NR; 33.9%
ESRD and Depression Evidence Synthesis Program

28

Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

Months on dialysis: 

46(65) 

Previous 

depression: 9.7%

Antidepressants: 

3.2%

Neitzer, 

201246

N = 134

US

CA, TX

2009

Multisite: outpatient 

HD units

48% Female

Age: 59.1(14.7)

AA/Black: 22%

Asian: 13%

White: 60%

Other: 4%

Education: NR

HD: 100%

Months on dialysis: 

Median = 27.5 (2.9-

252.2) 

History of 

depression: NR

Included: English or Spanish 

speaking, 18+ years old, due in April 

to June 2009 for their KDQOL-SF36 

assessment. 

Excluded: Questionnaires with 50% 

or more of the questions left blank 

were considered incomplete and 

excluded.

BDI-FS:

Self-report. Completed 

during HD treatment.

BDI-II: 

Completed during HD session. 

Order of completion was not 

specified.

BDI-FS≥ 4 = 

30.1%; BDI II ≥

16: 28.7%

1Preljevic, 

201236

N = 109

Norway

Multisite: hospitalbased HD and PD 

centers

30.3% Female

Age 57.8(15.7)

Race: NR

69.4% HS or less

HD: 76.6%; PD: 

23.3%

Months on dialysis: 

M=8.5 (3.75–22) 

History of 

depression: NR

Included: 18+ years receiving either 

HD or PD for more than 2 months, 

were in a stable clinical condition 

and had adequate Norwegian 

language skills.

Excluded: Cognitive dysfunction, 

psychosis or drug/alcohol abuse; 

hospitalization during the 

investigation period; however, they 

could be enrolled 4 weeks or more 

after discharge from hospital if they 

were in a stable clinical condition.

BDI, CDI, HADS-D:

Self-report. Completed in a 

standardized sequence 

during the dialysis treatment 

for HD patients and during 

the

routine outpatient control for 

PD patients.

SCID-I:

Administered by an experienced 

psychiatrist who was blinded to 

each participant's medical history 

and scores on all self-report 

questionnaires. Assessments 

were conducted during dialysis 

sessions to standardize the 

assessment procedure and the 

time point relative to dialysis 

treatment. Interviews were 

audiotaped and 25 randomly 

selected tapes were scored 

independently by another 

psychiatrist to establish inter-rater 

BDI≥16 = 20.8%, 

CDI≥11 = NR, 

HADS-D≥8 = 

20.1%; 22%

14.7% MDD
ESRD and Depression Evidence Synthesis Program

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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

reliability. The interrater reliability 

for depressive disorder was 

excellent (κ=1). Timing: NR

1Troidle, 

200347

N = 97

US

June 2000 – 

January 2002

Multisite: CPD and 

HD units

CP: 46% Female; 

HD: 40% Female

Age: CPD 

55.4(11.3); HD 

56(8.6)

White: CPD 75%; 

HD 87%

CPD: 83%; HD 17%

Education: NR

Dialysis duration: 

NR

History of 

depression: NR

NR 2 items from the KDQOL SF36:

Self-report. Likert 1-6. 

Scored by a social worker. 

Timing: consecutive

BDI: 

Self-report. Recorded by a social 

worker. Timing: consecutive

KDQOL SF-36 = 

NR; BDI-II ≥11 

NR

1Van den 

Beukel,51

2012

N = 133

Netherlands

Multisite: outpatient 

hospital-based 

dialysis units

39% Female

Age: 62(16)

Native Dutch: 66%

Education: NR

HD: 72%

Dialysis duration: 

NR

Previous 

Depression: 9%

Antidepressant: 6%

Months on dialysis: 

M=54(65)

Inclusion: 18+ years of age, ESRD 

for at least 30 days, able to read the 

Dutch language and had no 

significant visual, physical, or 

cognitive impairment that would 

prevent completion of the 

questionnaires

Exclusion: NR

MHI5 of the SF-36:

Self-report. Completed 

during dialysis. Timing: NR

BDI/CDI (Dutch Translation):

Self-report. Completed during 

dialysis. Timing: NR

MHI5≤70 = 39%; 

BDI-II ≥16 = 

23%, CDI≥10 = 

23%
ESRD and Depression Evidence Synthesis Program

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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

History of 

depression: NR

Watnick, 

200544

N = 62

US

Portland, OR

July 2003-

May 2004

Multisite: public and 

private outpatient 

HD and PD units 

(including VA)

Female: 32%

Age: 63(15)

AA/Black: 15%

Hispanic: 5%

Asian: 5%

White: 76%

Education: NR

HD: 95%, PD: 5%

Dialysis duration: 

NR 

History of 

depression: NR

Inclusion: 18+ years old and had 

started dialysis therapy more than 90 

days before enrollment. 

Exclusion: Did not speak English, 

MMSE ≤17, medical record 

documentation of a psychiatric 

diagnosis other than depression, 

were deemed unable to participate 

by the dialysis staff, or were 

scheduled for kidney transplant 

within the next month.

BDI, PHQ-9:

Self-report.

SCID-I:

Interviewed by a mental health 

professional (completed 

psychology internship), blinded to 

BDI/PHQ-9 results. Timing: within 

2 weeks of index tests. 

BDI, PHQ-9 = 

NR; 19.4%

1Wang, 

201945

N = 319

China

Multisite: hospitalbased HD units

31.4% Female 

depressed; 43.78% 

Female nondepressed

Age: 49.4 (6.04) 

depressed; 

50.92(6.46) nondepressed

Race: NR

HS or less: 51.44% 

depressed; 57.78% 

non-depressed

HD:100%

Inclusion: 18+ years of age; history 

of maintenance HD >3 months; 

ability to understand written Chinese, 

complete the interview and the 

questionnaire, and provide informed 

consent

Excluded: documented cognitive 

impairment, had another primary 

diagnosis (eg chronic heart failure, 

cancer, hyperthyroidism), or had 

been previously diagnosed with 

depression and other psychiatric 

disorders

BDI, DI-MHD:

Self-report. Timing: 2 weeks 

after clinical interview

SCID-I (ref for BDI):

Administered by a psychologist 

and a nephrologist. Timing: 2 

weeks before index tests.

BDI-II (ref for DI-MHD): 

Same time as index test.

BDI≥19 = 20.7%, 

DI-MHD≥25 = 

20%; 21.9%
ESRD and Depression Evidence Synthesis Program

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Author, Year

N enrolled

Country/ US 

region, 

years of 

enrollment

Study setting

Sample 

characteristics and 

demographics

Inclusion Criteria/ Exclusion 

Criteria 

Index Test(s); 

Administration

Reference Standard; 

Administration

% MDD Positive 

per Index Test; 

Reference 

Standard

Dialysis duration: 

NR

History of 

depression: NR 1 Screened for depressive symptoms or milder forms of depression in addition to Major Depressive Disorder. 2 Included cutoff values for both Major Depressive Disorder as well 

as for milder forms of depression and subclinical symptoms.

Abbreviations: BDI-II = Beck Depression Inventory – II; BDI-FS = Beck Depression Inventory - Fast Screen; CA = California; CDI = Cognitive Depression Index; CES-D = 

Center for Epidemiologic Studies – Depression Scale; CVD = cardiovascular disease; DI-MHD = Depression Inventory – Maintenance Hemodialysis; ESAS = Edmonton 

Symptom Assessment System; ESRD = end-stage renal disease; GDS-15= Geriatric Depression Scale-15 ; HADS-D = Hospital Anxiety and Depression Scale - Depressive 

Subscale; Ham-D= Hamilton Depression Rating Scale; HD = hemodialysis; HS = high school; ICD-10 = 10th revision of the International Statistical Classification of Diseases and 

Related Health Problems; KDQOL SF-36 = Kidney Disease Quality of Life Short Form - 36; MDD = major depressive disorder; MHI5 = Mental Health Inventory 5; NR = not 

reported; MINI = Mini International Neuropsychiatric Interview; MMSE = Mini-Mental Status Examination; NR = Not reported; NC = North Carolina; OR = Oregon; PD = 

peritoneal dialysis; PHQ-9= Patient Health Questionnaire 9; SCID-I= Structured Clinical Interview for DSM-IV; SF-36 = Kidney Disease Quality of Life Short Form - 36; SRQ = 

Self-Reporting Questionnaire; TX = Texas; UK = United Kingdom; US = United States; VA = Veterans Affairs
ESRD and Depression Evidence Synthesis Program

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Table 3. Findings of studies examining the diagnostic accuracy of depression screening 

tools in patients with ESRD

Author, Year

N enrolled

Cuto

ff

Sen

s 

(%)

Spe

c 

(%)

PPV 

(%)

NPV 

(%)

AU

C Summary of Findings

Beck Depression Inventory-II (BDI-II)

Balogun, 

201139

N = 96

≥10 68 77 57 85 0.73 Compared to diagnostic interview, the BDI-II 

cutoff with the best diagnostic accuracy was 

≥10.

Bautovich, 

201848

N = 45

≥18 100 90 60 100 0.99 Compared to diagnostic interview, the BDI-II is 

an acceptable screening tool, with a cutoff of 

≥18.

Chilcot, 

200853

N = 40

≥16 88.9 87.1 88.8 87 0.96

1 

Consistent with previous research, (off dialysis) 

BDI-II with a cutoff of ≥16 has good diagnostic 

accuracy.

2Grant, 

200850

N = 57

≥10 100 50 21.9 100 0.93 Using the general population cut-off score 

(≥10), the BDI-II significantly over-diagnosed 

depression in this HD population. A cutoff of 

≥15 is more reliable.

≥15 100 78 NR NR 0.93 

≥20 71.4 92 NR NR 0.93 

1Hedayati, 

200633

N = 98

≥14 62 81 53 85 0.77 When used for screening, the threshold for 

depression should be higher for ESRD 

compared with non-ESRD patients (ie, ≥14).

1Loosman, 

201035

N = 62

≥13 75 90.2 75 90.2 0.90 At a cutoff of ≥13, the BDI-II is an effective 

screening tool for depression in depression in 

ESRD patients. 

1Preljevic, 

201236

N = 109

≥12 91 63 39 96 0.92 The BDI-II demonstrated acceptable 

performance as a screening tool for 

depression. At a threshold of ≥16 (general 

population) the BDI-II performed better than 

the HADS and the CDI; however, a cutoff of 

≥17 is more reliable for this population.

≥13 91 68 43 97 0.92

≥14 86 71 44 95 0.92

≥15 82 75 46 94 0.92

≥16 82 87 62 95 0.92

≥17 82 89 67 95 0.92

≥18 77 92 71 94 0.92

1Wang, 

201945

N = 319

≥15 87 49 34 93 0.84 A cutoff of ≥19 indicated depression in this 

population. ≥16 87 58 39 94 0.84

≥17 87 65 43 94 0.84

≥18 87 71 47 95 0.84

≥19 83 86 63 94 0.84

≥20 74 94 77 92 0.84

Watnick, 

200544

N = 62

≥16 91 86 59 98 0.93

7 

The BDI-II ≥16 is a valid measure for 

depressive disorders in the dialysis population. 

Cognitive Depression Index (CDI)

Bautovich, 

201848

N = 45

≥11 100 92 67 10 0.98 Compared to diagnostic interview, the CDI ≥11 

is an acceptable screening tool.
ESRD and Depression Evidence Synthesis Program

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Author, Year

N enrolled

Cuto

ff

Sen

s 

(%)

Spe

c 

(%)

PPV 

(%)

NPV 

(%)

AU

C Summary of Findings

1Hedayati, 

200633

N = 98

≥8 50 83 52 82 0.76 When used for screening, the threshold for 

depression should be higher for ESRD 

compared with non-ESRD patients. The BDI-II 

or the CESD have better sensitivity and better 

agreement (kappa) than the CDI (cutoff ≥8).

1Preljevic, 

201236

N = 109

≥9 82 79 50 94 0.89 The CDI (cutoff ≥11) demonstrated acceptable 

performance as a screening tool for 

depression. The BDI-II performed better than 

the CDI. 

≥10 82 86 60 95 0.89

≥11 82 93 75 95 0.89

≥12 77 95 81 94 0.89

≥13 50 98 85 88 0.89

≥14 41 98 82 86 0.89

Center for Epidemiologic Studies – Depression Scale (CES-D)

1Hedayati, 

200633

N = 98

≥18 69 83 60 88 0.86 When used for screening, the CESD threshold 

for depression should be higher (≥18) for 

ESRD compared with non-ESRD patients. 

Geriatric Depression Scale-15 (GDS-15)

Balogun, 

201139

N = 96

≥5 63 82 60 83 0.81 The GDS-15 ≥5 is a valid tool compared to the 

gold standard.

Hamilton Depression Rating Scale (Ham-D)

1Gencoz, 

200742

N = 45

≥10 100 80 59 100 85 The HDRS ≥10 is a reliable and valid 

instrument that can be used among ESRD 

patients undergoing HD 

Hospital Anxiety and Depression Scale - Depressive Subscale (HADS-D)

1Loosman, 

201035

N = 62

≥6 90.5 75.6 85.7 75.6 0.89 The HADS-D ≥6 is an effective screening tool 

for depression in depression in ESRD patients. 

1Preljevic, 

201236

N = 109

≥4 100 48 33 100 0.91 At a HADS-D threshold of ≥8 the BDI-II 

performed better. ≥5 95 60 38 98 0.91

≥6 95 73 48 98 0.91

≥7 86 84 58 96 0.91

≥8 73 87 59 93 0.91

≥9 59 92 65 90 0.91

≥10 59 94 72 90 0.91

≥11 50 96 79 88 0.91

Patient Health Questionnaire 9 (PHQ-9)

Watnick, 

200544

N = 62

≥10 92 92 71 98 0.94 The PHQ-9 ≥10 is a valid measure for 

depressive disorders in the dialysis population. 

Self-Reporting Questionnaire (SRQ)

≥8 100 50 26 NR 0.96
ESRD and Depression Evidence Synthesis Program

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Author, Year

N enrolled

Cuto

ff

Sen

s 

(%)

Spe

c 

(%)

PPV 

(%)

NPV 

(%)

AU

C Summary of Findings

Alsuwaida, 

200652

N = 26

≥9/1

0

100 68 36 NR 0.96 The SRQ has high sensitivity the PPV is poor 

due to the somatic symptoms in nondepressed patients with ESRD. A cutoff of ≥13 

results in an acceptable specificity level without 

compromising sensitivity.

≥11/

12

100 72 40 NR 0.96

≥13 100 82 50 NR 0.96

≥14/

15

75 91 60 NR 0.96

≥16/

17

75 95.5 75 NR 0.96

≥18 75 100 100 NR 0.96

1 Screened for depressive symptoms or milder forms of depression in addition to Major Depressive Disorder. 

2 Included cutoff values for both Major Depressive Disorder as well as for milder forms of depression and 

subclinical symptoms. 

Abbreviations: AUC = Area under (receiver operating characteristic [ROC]) curve; BDI-II = Beck Depression 

Inventory – II; CDI = Cognitive Depression Index; CES-D = Center for Epidemiologic Studies – Depression Scale; 

GDS-15 = Geriatric Depression Scale-15; HADS-D = Hospital Anxiety and Depression Scale - Depressive 

Subscale; Ham-D = Hamilton Depression Rating Scale; NPV = Negative predictive value; NR = Not reported; PHQ9 = Patient Health Questionnaire 9; PPV = Positive predictive value; Sens = sensitivity; Spec = specificity; SRQ = 

Self-Reporting Questionnaire
ESRD and Depression Evidence Synthesis Program

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Diagnostic Accuracy Studies: A Primer

The performance of a diagnostic test is described by its sensitivity and specificity, along with 

the positive and negative predictive values. Depression assessment tools generate outcomes 

along a continuous scale, much like a lab test such as the thyroid stimulating hormone. Usually, 

there is a trade-off between sensitivity and specificity: at lower diagnostic thresholds (ie, lower 

scores on a depression instrument in which higher scores indicate more symptoms) one is more 

likely to capture all patients that have depression (ie, higher sensitivity) but there are also likely 

to be more false positive tests (ie, lower specificity). The area under the receiver operating 

curve (AUC) describes a test’s overall performance and its ability to correctly distinguish 

patients with and without disease across a range of diagnostic thresholds. Generally, tests with 

higher AUC are better able to discriminate patients with and without disease, though tests with 

similar AUC can still perform differently at different diagnostic thresholds. The choice of 

diagnostic instrument and diagnostic threshold depends in part on how important it is to detect 

all patients with disease (which might be very important for treatable and potentially fatal 

conditions), how important it is to minimize the risk of false positives (ie, because treatment of 

the condition is potentially harmful, burdensome, or costly), and to what extent the diagnostic 

test has been evaluated in the population of interest (Veterans in the United States with ESRD, 

in this case). 

Summary of Findings

Diagnostic Accuracy by Screening Tool

Beck Depression Inventory-II (BDI-II)

The BDI-II is a widely used, validated 21-item self-report tool designed to assess depression 

severity in adolescents and adults, and was by far the most widely studied instrument in the 

ESRD population. It closely mirrors DSM-IV criteria for major depressive disorder, and includes 

questions related to cognitive, affective, and somatic symptoms.27 

Table 4 lists the performance characteristics of 5 studies examining the accuracy of the BDI-II in 

diagnosing Major Depressive Disorder compared to a gold standard clinical interview (eg, SCIDI).39,44,48,50,53 Sample sizes ranged from N = 4053 to N = 96.39 Two of the 5 studies were 

conducted in the United States.39,44 One was a small, multicenter study that included 1 VHA site 

(N = 62), and reported an optimal BDI-II cutoff of ≥16. Sensitivity was 0.91 and specificity was 

0.86, with an AUC of 0.94.44 The second was a multicenter study of adults 65 and older (N = 

96). At a cutoff of ≥10, sensitivity was 0.68, specificity was 0.77, and reported AUC was 0.73 

(see Table 2 for study details).39

One study in Table 4 reported BDI-II performance across a range of thresholds.50 The threshold 

that optimized the sensitivity and specificity of the BDI-II for MDD was ≥15, with a reported 

area under the receiver operating curve (AUC) of 0.93. One study reported an AUC that was 

much lower than the others.39 This study’s population was limited to older adults, and it is 

possible that age differences may have contributed to the difference in performance 

characteristics (see Table 2 for study details).39
ESRD and Depression Evidence Synthesis Program

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Table 4. Beck Depression Inventory-II (BDI-II) characteristics by threshold among studies 

screening for Major Depressive Disorder (MDD)

Threshold Sensitivity (%) Specificity (%) PPV (%) NPV (%) AUC

≥1039,50 68 77 57 85 0.73

100 50 21.9 100 0.93 

≥1550 100 78 NR NR 0.93 

≥1644,53 88.9 87.1 88.8 87 0.961

91 86 59 98 0.937

≥1848 100 90 60 100 0.99

≥2050 71.4 92 NR NR 0.93 

Abbreviations: AUC = Area under (receiver operating characteristic [ROC]) curve; BDI-II = Beck Depression 

Inventory-II; NPV = Negative predictive value; NR = Not reported; PPV = Positive predictive value

Table 5 also lists performance characteristics for the BDI-II, but unlike the studies in Table 4, 

these 4 studies screened for depressive symptoms and disorders ranging from subclinical to 

MDD.35,36,45,56 Sample sizes ranged from N = 4353 to N = 319.45 Only 1 study (N = 98) was 

conducted in the United States, with 1 of the 3 sites at a VHA.56 At a threshold of ≥14, sensitivity 

was 0.62, specificity was 0.81, and reported AUC was 0.77. The largest study (N = 319), 

conducted in China, compared the BDI-II (≥19) to the SCID-I as part of a development and 

validation study for a depression tool designed specifically for patients undergoing maintenance 

hemodialysis.45 Sensitivity, specificity, PPV, NPV, and AUC were 0.83, 0.86, 63%, 94%, and 

0.84 respectively (see Table 2 for study details).

Table 5. Beck Depression Inventory-II (BDI-II) characteristics by threshold among studies 

screening for Major Depressive Disorder (MDD) and less severe depression 

Threshold Sensitivity 

(%)

Specificity 

(%) PPV (%) NPV (%) AUC

≥1236 91 63 39 96 0.92

≥1335,36 75 90.2 75 90.2 0.90 

91 68 43 97 0.92

≥1456,36 62 81 53 85 0.77

86 71 44 95 0.92

≥1536,45 82 75 46 94 0.92

87 49 34 93 0.84

≥1636,45 82 87 62 95 0.92

87 58 39 94 0.84

≥1736,45 82 89 67 95 0.92

87 65 43 94 0.84

≥1836,45 77 92 71 94 0.92

87 71 47 95 0.84

≥1945 83 86 63 94 0.84

≥2045 74 94 77 92 0.84

Abbreviations: AUC = Area under (receiver operating characteristic [ROC]) curve; BDI-II = Beck Depression 

Inventory-II; NPV = Negative predictive value; NR = Not reported; PPV = Positive predictive value
ESRD and Depression Evidence Synthesis Program

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Cognitive Depression Index (CDI)

The CGI is a subset of the BDI and includes the first 15 of the 21-items included in the BDI, 

eliminating items related to somatic symptoms. It was developed for use in patients with Chronic 

Kidney Disease, with the goal of reducing the likelihood of the overdiagnosis of depression.57

Three studies compared the performance characteristics of the CGI to a gold standard clinical 

interview,

36,48,56 of which only 1 screened for major depressive disorder (N = 45; cutoff ≥10).48

Sensitivity and specificity values, and AUC were 0.79, 0.81, and 0.94 respectively (see Tables 2 

and 3).48

The 2 studies screening for the range of depressive symptoms and diagnoses examined cutoff 

values of ≥8 (N = 98)56 and ≥11 (N = 109).36 Sensitivity values were 0.5056 and 0.82,36

specificity was 0.8356 and 0.93,36 and AUC was 0.7656 and 0.89 (see Tables 2 and 3).36 Of note, 1 

study36 examined both the BDI at a threshold of ≥16 and CDI (≥11) and found that the BDI 

performed better.

Hospital Anxiety and Depression Scale – Depression Subscale (HADS-D)

The Hospital Anxiety and Depression Scale – Depression Subscale (HADS-D) is a widely-used 

21-item scale that includes ratings of physical, cognitive, and affective symptoms of 

depression.34

Two studies examined the performance characteristics of the HADS-D in patients with 

ESRD.35,36 Both studies also screened for less severe depression diagnoses and/or subclinical 

symptoms. One study (N = 62) examined a cutoff value of ≥6 and found sensitivity, specificity, 

and AUC values of 0.91, 0.76, and 0.89 respectively. 35 The other (N = 109), examined a cutoff 

value of ≥8 and reported sensitivity, specificity, and AUC values of 0.73, 0.87, and 0.91 

respectively. Of note, this study also examined the BDI and found that it performed better (≥16; 

see Tables 2 and 3).

36

Center for Epidemiologic Studies – Depression Scale (CES-D)

The CES-D is a widely used 20-item tool that was revised in 2004 and evaluates depressive 

symptoms across 4 factors: depressive affect, well-being, somatic symptoms, and interpersonal 

relations.

32

A 3-center multisite study (1 VHA; N = 98)56 compared the CES-D (≥18) to the SCID-I for 

MDD and other less severe forms of depression and subclinical symptoms. Sensitivity, 

specificity, and AUC were 0.69, 0.83, and 0.89 respectively (see Tables 2 and 3).

Hamilton Depression Rating Scale (Ham-D)

The Ham-D is a 17-item rating scale that assesses the frequency and intensity of depressive 

symptoms. It was developed in 1960, and last revised in 1967.41

A single small study (N = 45) conducted in Turkey compared the HAM-D (≥10) to the SCID-I in 

patients with ESRD undergoing hemodialysis and screened for the range of depressive symptoms 
ESRD and Depression Evidence Synthesis Program

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and disorders. Reported sensitivity was 1.00, specificity, 0.80, and AUC was 0.85 (see Tables 2

and 3).42

Geriatric Depression Scale-15 (GDS-15)

The GDS-15 is a shortened version of the original 30-item GDS, which assesses depressive 

symptoms in older adults and was developed in 1982.37,38

One study (N = 96) compared the GDS-15 (≥5) in older adults with ESRD to a gold standard 

clinical interview for MDD. Sensitivity was 0.62, specificity was 0.82, and AUC was 0.81 (see 

Tables 2 and 3).

39

Patient Health Questionnaire-9 (PHQ-9)

The PHQ-9 was developed in 2001 to be a short form assessment of depression and severity. It is 

widely used in the US and internationally.43

One small multisite study (N = 62) that included a VHA center examined the PHQ-9 (≥10) 

compared to the gold standard SCID for MDD. Sensitivity and specificity were both 0.92, and 

AUC was 0.94 (see Tables 2 and 3).44

Self-Reporting Questionnaire (SRQ)

The SRQ was developed by the World Health Organization (WHO) to screen for a range of 

mental health disorders.58

A single very small study (N = 26) conducted in Saudi Arabia compared the SRQ (≥13) to the 

gold standard SCID-I in patients with ESRD for MDD. Sensitivity, specificity, and AUC were 

1.00, 0.82, and 0.96 respectively (see Tables 2 and 3).52

Screening Tools Compared to Other Tools

Seven studies used other established tools (ie, BDI-II, HADS) as reference standards.

40,45-

47,49,51,53 Table 6 lists their performance characteristics. Only 2 studies screened for MDD 

specifically, both evaluating shortened versions of the BDI-II (BDI-II Fast Screen [BDI-FS], 

CDI).46,53 Of the 2, the BDI-FS,59 a 7-item version of the BDI-II that excludes somatic symptoms 

and was designed to screen for MDD in medical patients, had high sensitivity and specificity as 

compared to the BDI-II ≥16.

46 Among those screening for the range of depressive symptoms and 

disorders, the GDS-15 (≥6)

46 and the Depression Inventory – Maintenance Hemodialysis (DIMHD; ≥25), a scale developed specifically for patients with ESRD,45 appear to perform well in 

this population (see Table 2 for study details).
ESRD and Depression Evidence Synthesis Program

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Table 6. Studies comparing a depression tool to another validated depression tool

Author, Year

N enrolled Cutoff Sens (%)

Spec 

(%)

PPV 

(%)

NPV 

(%) AUC Summary of Findings

Beck Depression Inventory – Fast Screen (BDI-FS)

Neitzer, 201246

N = 134

≥4 97.2 91.8 81.4 98.9 0.98 Reference standard: 

BDI-II ≥16

Cognitive Depression Index (CDI)

Chilcot, 200853

N = 40

≥10 77.8 80.6 77.7 80.6 0.94 Reference standard: 

BDI-II ≥16

Depression Inventory – Maintenance Hemodialysis (DI-MHD) 

1Wang, 201945

N = 319

≥23 97 55 84 89 0.94 Reference standard: 

BDI-II ≥19 ≥24 97 72 90 91 0.94

≥25 97 86 95 93 0.94

≥26 93 90 96 84 0.94

≥27 85 90 95 70 0.94

Edmonton Symptom Assessment System (ESAS) – single question

1Collister, 201949

N = 50

≥2 81 74 NR NR 0.81 Reference standard: 

HADS ≥6. 

Geriatric Depression Scale-15 (GDS-15)

1Giordano, 200740

N = 31

≥6 94 85 89 92 0.95 Reference standard: 

BDI-II ≥14. 

Kidney Disease Quality of Life Short Form - 36 (KDQOL SF-36) “Have you felt downhearted and blue?”

1Troidle, 200347

N = 97

≤3 82 69 NR NR NR Reference standard: 

BDI-II ≥11.

Kidney Disease Quality of Life Short Form - 36 (KDQOL SF-36) “Have you felt so down in the dumps so 

that nothing could cheer you?”

1Troidle, 200347

N = 97

≤3 65 67 NR NR NR Reference standard: 

BDI-II ≥11.

Mental Health Inventory 5 (MHI5)

1Van den Beukel, 

201251

N = 133

≥66 67 78 NR NR 0.82 Reference standard: 

BDI-II ≥16 (≥66+) and 

CDI≥10 (≥74+)

≥70 77 72 44 91 0.82

≥74 83 

81 CDI

65

65 CDI

NR NR 0.82

0.81 

CDI

≥78 90 54 NR NR 0.82

≥82 93 45 NR NR 0.82

1 Screened for depressive symptoms or milder forms of depression in addition to Major Depressive Disorder.

Abbreviations: AUC = Area under (receiver operating characteristic[ROC]) curve; BDI-II = Beck Depression 

Inventory – II; BDI -FS = Beck Depression Inventory - Fast Screen; CDI = Cognitive Depression Index; DI-MHD =

Depression Inventory – Maintenance Hemodialysis; ESAS = Edmonton Symptom Assessment System; GDS-15 = 

Geriatric Depression Scale-15; HADS-D = Hospital Anxiety and Depression Scale - Depressive Subscale; KDQOL36 = Kidney Disease Quality of Life Short Form - 36; MHI5 = Mental Health Inventory 5; NPV = Negative 

predictive value; NR = Not reported; PHQ-9 = Patient Health Questionnaire 9; PPV = Positive predictive value; 

Sens = sensitivity; Spec = specificity; SRQ = Self-Reporting Questionnaire 
ESRD and Depression Evidence Synthesis Program

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Ongoing studies

No ongoing studies were identified.

KEY QUESTION 2: What is the impact of screening for depression in 

patients with ESRD on intermediate and/or patient outcomes?

No studies were identified to provide evidence for Key Question 2.

KEY QUESTION 3. What is the effectiveness of depression treatment 

in patients with ESRD and depression?

We identified 20 RCTs examining pharmacological or nonpharmacologic interventions for the 

treatment of depression in patients with ESRD. Five trials examined selective serotonin reuptake 

inhibitors (SSRIs), including 3 of sertraline and 1 each of fluoxetine and citalopram; 2 trials 

examined nutritional supplements including omega-3 fatty acids and high-dose, oral vitamin D3.

Thirteen trials examined nonpharmacologic interventions including 5 trials of CBT, 2 

acupressure trials, and 1 each of Benson Relaxation Technique, exercise training, guided 

imagery, hope therapy, Latihan Pasrah Diri, Mindfulness-based Stress Reduction (MBSR), and 

Quran readings. All studies were of participants receiving HD. A single study included both 

patients receiving HD and PD (see Table 7).

Summary of findings

A. Pharmacological treatment

We identified 7 RCTs examining pharmacological interventions for depression in participants 

with ESRD. There was low SOE that there is no difference in depression severity reduction 

between sertraline and CBT, though both are beneficial. Regarding dietary supplements, there 

was moderate SOE that long-term, high-dose Vitamin D3 is not effective for reducing depression 

severity in ESRD patients. Findings for all other pharmacotherapies were insufficient to draw 

conclusions.

SSRIs

The data to guide the treatment of depression in patients with ESRD with SSRIs is limited. We 

identified 5 RCTs investigating the effects of SSRIs on depression – 3 comparing SSRIs to 

placebo and 2 comparing SSRIs to an active comparator. 

SSRIs versus placebo

Studies comparing SSRIs to placebo report conflicting findings and provide insufficient evidence 

for the use of SSRIs to treat depression in patients with ESRD. A small (N = 14), poor-quality 

RCT60 conducted in 1997 compared fluoxetine to placebo. At 4 weeks, participants receiving 

fluoxetine reported a significantly larger reduction in depressive symptoms from baseline, 

compared to placebo. However, by 8 weeks the differences were no longer significant. A more 

recent, fair-quality RCT (N = 30)61 in England compared sertraline to placebo and found that 

although both groups reported a reduction in depressive symptoms, there was no difference 

between groups at the end of treatment (6 months) or 6-month follow up. A second, larger fair-
ESRD and Depression Evidence Synthesis Program

41

quality RCT (N = 50)62 conducted in Iran also compared sertraline to placebo. Participants who 

received sertraline reported a significant reduction in depressive symptoms at 12 weeks (see

Tables 7 and 8). Overall, these fair- to poor-quality studies provide insufficient evidence for the 

use of SSRIs to treat depression in patients with ESRD (see Table 10). Studies were hampered 

by small sample sizes, and differences in depression assessment tools and statistical analyses (see 

Table 9). 

SSRIs versus active comparators

A recent fair-quality multi-site US study by Mehrotra et al (N = 120)63 compared sertraline to 

CBT. The primary outcome was clinician-rated depression measured with the QIDS-C, and both 

groups improved over 12 weeks. However, the sertraline group experienced significantly greater 

improvement (effect estimate: −1.85; 95% CI: −3.55 to −0.16]). For the secondary endpoint of 

self-rated depression (BDI-II) the difference between the groups was not significant (effect 

estimate: −2.9 [95% CI: −6.7 to 0.8]). The strength of evidence for this comparison was low (see 

Tables 7, 8, and 9). 

A poor-quality RCT (N = 44)64 conducted in Iran provides insufficient evidence for the 

comparison of citalopram to “psychological training” in depressed patients with ESRD. 

Although both arms experienced a reduction in depressive symptoms, there was no difference 

between citalopram and the comparator (see Tables 7, 8, and 9). 

Supplements

Two RCTs compared supplements to placebo for the treatment of depression in ESRD patients. 

A large (N = 746), fair-quality, 52-week RCT65 conducted in Southeast China compared ESRD 

patients (treated with either HD or PD) receiving either high-dose vitamin D3 or placebo. Both 

arms reported a reduction in depression symptoms at 52 weeks with no significant difference 

between groups (see Tables 7 and 8). Given the size and quality of the study, the strength of 

evidence is moderate that long-term, high-dose vitamin D3 is an ineffective treatment for

depression in patients with ESRD (see Table 9).

A single, poor-quality RCT (N = 54),

66 conducted in Iran, examined the effect of omega-3 fatty 

acids versus placebo. Findings indicate a significant reduction in depression symptoms in the 

treatment arm at 4 months, and no change was associated with placebo. The evidence is 

insufficient to form conclusions (see Tables 7, 8, and 9).

B. Non-pharmacological treatment

We identified 13 RCTs examining non-pharmacological interventions for depression in 

participants with ESRD. There was low SOE that CBT is more effective than other 

psychotherapy for depression severity and QOL, but not for suicide risk. CBT was also more 

effective than placebo for depression severity and QOL (low SOE). There was also low SOE for 

acupressure reducing depression severity when compared with usual treatment or sham 

acupressure. Findings for all other non-pharmacological interventions were insufficient to draw 

conclusions.
ESRD and Depression Evidence Synthesis Program

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Cognitive Behavioral Therapy

Five RCTs investigated CBT for the treatment of depression in patients with ESRD. 

CBT versus active comparator

We identified 3 RCTs that compared CBT to an active comparator for the treatment of 

depression in patients with ESRD. A fair-quality RCT (N = 90)67 conducted in Brazil compared 

group CBT to individualized psychotherapy for participants with MDD, and found a greater 

reduction in depression symptoms (both clinician and self-reported) associated with CBT (BDIII: P = 0.001 after 3 months of treatment, P = 0.002 at 9 months follow-up; MINI: P < 0.001 after 

3 months of treatment. P = 0.031 at 9 months follow-up; low SOE). In addition, participants 

receiving CBT also experienced a significant within group decrease in suicide risk and improved 

on several quality-of-life domains over the study period, while the those assigned to 

psychotherapy did not. However, the between-group difference in suicide risk reduction was 

nonsignificant (low SOE). At the end of the study period, there was a significant difference 

favoring CBT in several quality of life domains (ie, burden of kidney disease, quality of social 

interaction, sleep, overall health, and the mental health; low SOE; see Tables 7, 8, and 9).

Two other trials compared CBT to an active comparator. A poor-quality Jordanian RCT (N = 

130)68 compared CBT to psychoeducation, and while both groups reported a reduction in

depression symptoms, the psychoeducation group experienced greater improvement. The 

strength of evidence for this comparison is insufficient. The third study by Mehrotra and 

colleagues63 was also included in the pharmacotherapy section because it examined CBT versus 

sertraline for treatment-seeking participants with ESRD and depression. For the primary outcome 

of clinician-rated depression severity, both groups experienced improvement, but sertraline was 

more effective than CBT. However, there was no difference between the CBT and sertraline 

groups in self-reported depression severity, and the strength of evidence was low (see Tables 7, 

8, and 9).

CBT versus control

Two fair-quality RCTs69,70 provide low-strength evidence of CBT’s benefit when compared with 

waitlist control. A fair-quality, New York-based RCT (N = 65) examined individual CBT during

dialysis and found a greater magnitude of reduction in depression symptoms (P = 0.03) and a 

significant improvement in quality of life (P = 0.04) among those receiving CBT compared with 

those on the waitlist.

69 The study also found that fluid adherence was improved for the CBT 

group at all timepoints, but the strength of evidence for that comparison is insufficient. The 

second study was a fair-quality RCT (N = 60) examining once-weekly group CBT sessions 

following dialysis in those with mild-moderate depression in a Mexican ESRD population.

Findings also indicate a significant reduction in depression and increased quality of life (low 

SOE; see Tables 7, 8, and 9).

70

Acupressure

Two RCTs contribute to low-strength evidence that acupressure is more effective than control 

for reducing depression severity in ESRD patients. Both studies used similar acupressure 

procedures. A fair-quality, 3-arm, Iranian RCT (N = 96)71 compared acupressure to sham 

acupressure (ie, pressure applied 1 cm from the acupressure point), and usual care. Participants 
ESRD and Depression Evidence Synthesis Program

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receiving acupressure reported a significantly greater reduction in depression symptoms 

compared to both sham and usual care (no difference between sham and usual care). A second 3-

arm poor quality RCT (N = 108)72 compared acupressure to transcutaneous Electrical Acupoints 

Stimulation (TEAS) and usual care in participants in Northern Taiwan. TEAS was applied to the 

same acupressure points and is theorized to have a similar effect to acupressure and 

acupuncture.72 Findings indicate a greater reduction in depressive symptoms and fatigue, and an 

improvement in sleep quality associated with both acupressure and TEAS than usual care (no 

significant difference between acupressure and TEAS). The evidence examining acupressure for 

fatigue and sleep quality is insufficient to draw conclusions (see Tables 7, 8, and 9).

Other treatments

We included RCTs of 7 other therapies: Benson Relaxation Technique,73 exercise training,74

guided imagery,75 hope therapy,76 Latihan Pasrah Diri (LPD),77 MBSR,78 and Quran readings for 

Muslim patients (see Tables 7, 8, and 9).79 All were small, single trials with methodological 

issues, and the evidence was insufficient for all of these treatments.

C. Pharmacological and non-pharmacological treatments combined

No trials addressing the combination of pharmacological and non-pharmacological treatments 

were identified.

Ongoing studies

We identified 3 relevant trials of depression treatments for patients with ESRD, all of which have 

not yet reported results or been published (see Table 10 for details).
ESRD and Depression Evidence Synthesis Program

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Table 7. Characteristics of randomized controlled trials of interventions for depression in ESRD outpatients 

Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Pharmacological

Blumenfield, 

199760

Fluoxetine

N = 14

New York, NY

Years: NR

2 sites: Hospital dialysis 

centers 

Demographics: NR

Included: 18-70 yrs old, normal liver function, score 

of at least 16 for MDD by Hamilton scale.

Excluded: chronic illness other than ESRD and 

DM, suicidal risk, Axis 1 dx except MDD, 

psychotropic meds other than Lorazepam, 

pregnant or not on contraception if child bearing 

age, MAOI in the past 2 weeks or participation in 

any drug trial within 4 weeks

Depression diagnosis: MDD

Psychiatrist administered 

HAM-D for dx; BDI; MADRS; 

Depression Scale of Brief 

Symptom Inventory; self-report 

VAS for severity of depression

NR

Friedli, 201761

Sertraline

N = 30

England 

April 2013 - 

May 2015

Multisite (5): Renal units

12% Female

Age: 61.7 (13.2)

Race: 67% white, 13% 

AA, 13% Asian, 7% 

mixed

Included: BDI-II score ≥16, diagnosed with mild to 

moderate MDD with MINI, and MADRS score ≥18

Excluded: current or past 3 months tx for 

depression (antidepressants or psychologic 

therapies), planned living donor kidney transplant 

within trial period, prognosis of <1 year, several 

associated medical conditions (Hepatic 

impairment, Hepatitis B and C, HIV/AIDS, 

Creutzfeldt–Jakob disease, pregnancy or 

childbearing potential and not using adequate birth 

control, substance dependency, psychosis, 

personality disorder, dementia, or panic disorder 

with the exception of other anxiety disorders), and 

contraindicated medications (Monoamine oxidase 

inhibitors, Pimozide, Triptans, Antipsychotics, 

Dopamine antagonists, Tramadol, Linezolid, 

Warfarin), those with severe depression or suicidal 

ideation, and cognitive impairment on the Folstein 

MMSE (cut point of 23).

Depression diagnosis: MDD

BDI-II; MINI; MADRS

patient completed BDI-II, then 

interviewed by psychiatrist for 

MINI

MADRS: 24.5 

(4.5) vs 25.3 

(4.2)
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Gharekhani, 

201466

Omega-3 fatty 

acid

N = 54 

Tehran, Iran

Year: NR

2 sites: HD Centers 

Duration: 70.7 +/- 45.1 

mos

4 hrs, 2-3x/wk 

48% Female

Age: 56.8 ± 13.09 yrs 

Included: Adults, TIW HD for at least 3 months and 

all had same HD rx

Excluded: BDI-II<16; pregnancy; current 

inflammatory or infectious diseases; malignancy; 

prognosis of <4 months; asthma or COPD; other 

known psychiatric disorders; hypothyroidism; 

hemoglobinopathies; concurrent involvement in 

other research studies; history of medical or 

surgical illness in past 3 months; previous 

medication or HD noncompliance; malabsorption 

syndrome; coagulopathies or increased risk of 

bleeding; need to take anticoagulant medications 

including warfarin; intake of omega-3 fatty acids 

supplement in recent 3 months; hypersensitivity to 

fish or fish-derived products; concurrent use of 

corticosteroid, immunosuppressive, 

immunomodulator, anti-depressant, antiepileptic 

(except gabapentin), anti-psychotic, or nonsteroidal 

anti-inflammatory medications

Depression diagnosis: Any

BDI-II; application details NR BDI-II: 23.52 ± 

7.49 

(Median/IQR: 

22 (17, 28)) vs 

21±4.72 

(Median/IQR: 

21 (16.50, 

22.75)).

Hosseini, 

201264

Citalopram

N = 44

Iran

Years NR

Single-site: hospital HD 

center 

55% female 

Age: 52.3 ± 15.6

Included: HADS≥8

Excluded: history of psychiatric disorders, 

stressors other than ESRD in past 6 months, new 

anxiety episode during study, based on the stress 

events table by Holmz-Rahe, any change occurred 

in the hemodialysis schedule, starting other 

psychiatric therapies during the study, those not 

completing all training sessions.

Depression diagnosis: Any

HADS: completed twice by the 

patients under the supervision 

of a psychiatrist, once before 

the random allocation of the 

patients and once months 

after the start of interventions

HADS: 9.42 ± 

3.11 vs 9.58 ± 

3.47
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Mehrotra, 

201963

Sertraline vs 

CBT

N = 120

US: NM, TX, 

WA

2017

Multisite (3 states): 41 

dialysis facilities

Median time since 

starting dialysis (IQR), 

mo: 31 (44)

Mean hemodialysis 

treatment time per 

session (±SD), h: 3.9 ± 

0.4

43% Female

Age: 51 ± 13

Race: 43% white; 28% 

Black; 28% Hispanic; 

8% Native Amer; 12% 

other

Education: 40% ≤ high 

school 

History of major

depression: 42%

Included: 21 ≥ y/o, ESRD, On HD ≥3 months, MDD 

or dysthymia (BDI-II ≥15, then confirmed by MINI)

Excluded: suicidal, receiving intensive 

psychotherapy for depression, or using 

medications with potential antidepressant effects at 

effective therapeutic doses, and those with 

cognitive impairment, present or past psychosis, or 

alcohol or substance use disorder

Depression diagnosis: MDD or dysthymia

BDI-II and MINI for screening. 

QIDS-SR during trial, and 

QIDS-C and BDI-II at 12 

weeks. Final QIDS-C and BDIII by computer-assisted 

telephone interviewing

QIDS-C mean 

(range): SERT 

10.9 (9.6 to 

12.1) vs CBT 

12.2 (11.0 to 

13.5)

BDI-II mean

(range): SERT 

25.8 (23.3 to 

28.4) vs CBT 

26.2 (23.6 to 

28.8)

Taraz, 201362

Sertraline

N = 50

Tehran, Iran

Years NR

Single site: outpatient 

HD clinic

HD for 4 hrs 3x/wk 43% 

Time on HD (months): 

42 (59) Female

Age: 60 (22)

all others NR

Included: 18 - 80 y/o, HD ≥3 months using 

arteriovenous fistula, depression diagnosis: BDI-II 

≥16

Excluded: inflammatory cause of ESRD, 

autoimmune diseases, active infections, 

malignancy, severe mental illness, cognitive 

dysfunction, hemorrhage/clotting disorders, 

hypersensitivity to sertraline, treatment with 

antibiotics, non-steroidal anti-inflammatory drugs, 

steroids, immunosuppressives, or antidepressant 

medications within 1 month before the study.

Depression diagnosis: Any

BDI-II; application details NR BDI-II: 29 (13) 

vs 23 (11); P = 

0.243
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Wang, 201665

Vitamin D3

N = 746 

Southeast 

China

Years NR

3 sites: Dialysis centers

HD and PD

Outpatient 

39% Female

Age: 54% 18-64; 46% 

65+

Other demographics: 

NR

Included: ESRD, current conventional maintenance 

PD (3 exchanges a day) or HD (3x/wk, 4–4.5 

hrs/session) ≥3 months, age ≥18 years, 15 to 30 

ng/mL plasma 25(OH)D BDI-II cutoff: 16

Excluded: cognitive deficits such as considerable 

memory loss, confusion/ dementia, and intellectual 

disability; illiteracy or inability to answer the 

questionnaire; antidepressants in 2 years before 

study; presence of severe depressive symptoms

before dialysis

Depression diagnosis: MDD, vascular depression

BDI-II-II: Structured interviews 

were conducted by 2 

experienced

psychiatrists independently to 

determine diagnoses and 

severity of depression for each 

patient.

BDI-II: 22.7 ± 

4.3 vs 21.9 ± 

5.4 (P = 0.31)

Non-pharmacological

Al Saraireh, 

201868

CBT vs PSE

N = 130

Jordan, 2017

Multisite: 5 hospital 

dialysis units

Dialysis duration: NR

~50% Female

Age: 52 ± 10.7

Education: 71% ≤ high 

school Employment: 

82% unemployed

Race/Insurance NR

Included: diagnosis of chronic kidney failure; 

chronic dialysis ≥1 year; verbal 

comprehension/communication 

Excluded: on antidepressants

Depression diagnosis: NR

HAM-D: Data collectors with 

previous experience on 

psychiatric research read the 

items of the instrument for the 

participants and documented 

their response.

HAM-D: PSE

19.6 ± 5.4 vs 

CBT 19.5 ± 5.4

No difference: 

t(103) = −0.13; 

P = 0.89

Babamohamad

i, 201779

Quran

N = 60

Iran, year NR

Single site: hospital 

dialysis ward

42.6% Female

Age: 53.3 (11.4)

Race: NR

Education: 75% less 

than diploma

Employment: NR 

(55.6% "poor")

Insurance: NR

Included: 18-65 y/o; BDI-II score ≥20; command of 

Arabic; HD for ≥6 months; hemodynamic stable

Excluded: using antidepressants, acute mental 

problems, history of mental illness, impaired 

consciousness, hearing impairment 

Depression diagnosis: moderate

BDI-II-II: self-completed before 

start of dialysis/first session, 

and again after the last one

BDI-II-II: 33.6 

(6.7) vs 29.3 

(9.0); mean 

difference: -4.3 

(95% CI: -8.7 

to 0.0) P = 0.05
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Beizaee, 

201875

Guided 

Imagery

N = 80

Iran, 2015-

2016

Single-site: HD center

Sex: 41.25% Female

Age: 47.21(8.34)

Education: 46.25% 

Secondary

Employment: 25% 

unemployed

Included: HD 3x/wk for ≥6 months; 35-65 y/o; 

read/write in Farsi, intact cognitive functions based 

on Abbreviated Mental Test (AMT)

Excluded: hearing impairment, history of 

psychiatric disorders, taking tranquillizer or 

sedative drugs 4h before the intervention, and 

hemodialysis instability.

Depression diagnosis: Any

HADS: completed before and 

after intervention

HADS: 10.82 ± 

2.70 vs 11.55 ± 

2.29

Cukor, 201469

N = 65

CBT

Brooklyn, NY, 

year NR

2 sites: dialysis units

72.7% Female

Age: NR

Race: 93.9% Black

Education: 11.2 (3.4) yrs

Employment: 83.4% 

Unemployed

Insurance: NR

Included: ESRD with HD for ≥6 months; BDI-II 

score ≥10

Excluded: current hospitalization, altered mental 

status (MMSE <23), psychosis, current substance 

abuse, current ongoing psychotherapy, change in 

psychotropic medication in last 6 months, lack of 

English proficiency to participate in talk therapy

Depression diagnosis: Moderate

BDI-II-II (self-reported), HAMD (clinician assessed), and 

SCID-I (major depression): 

Applied before randomization 

and after 3 and 6 months

SCID-I % w/ 

major 

depression: 

54.5 vs 42.2

BDI-II: 25.3 

(9.3) vs 21.4 

(8.9)

HAM-D: 15.0 

(6.2) vs 13.5 

(5.0)

Duarte, 200967

CBT

N = 90

Brazil, year NR

2 sites: dialysis units

HD: 3x/wk for 4 hrs avg.

63.4% Female

Age: 52.4±15.9

Race: 78.1% white

Education: 83% ≤ 

primary school

Employment/Insurance: 

NR 

Included: ESRD with HD for ≥3 months; MINI MDD 

diagnosis

Excluded: transplant scheduled, current 

hospitalization, psychiatric comorbidity (Axis I 

DSM-IV), cognitive or mental retardation, current 

substance abuse, or unstable clinical condition 

Depression diagnosis: MDD

BDI-II and MINI: 

questionnaires administered 

and rated by trained 

psychologist immediately 

before the start of the 

intervention, after 3 months, 

and at the end of 9 months

BDI-II: 

24.2±9.7 vs 

27.3±10.7 (P = 

0.149)

MINI: 6.4±1.3 

vs 6.4±1.2 (P = 

0.955)
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Heshmatifar, 

201573

Benson 

Relaxation 

Technique

N = 70

Iran, 2013

Single site: hospital HD 

unit

HD: 3x/wk

18% Female

Age: 9% 18-35; 33% 35-

45; 45% 45-55; 15% 55-

65 

Race: NR

Education: 94% ≤ high 

school

Employment: 42% 

Unemployed

Insurance: NR

Included: 18-65 y/o; HD 3x/wk for ≥6 months; 

regular patient of the center

Excluded: mental/muscular disorders or severe 

physical disabilities; mental health medication use; 

history of depression or hospitalization due to 

mental disorders before CHD and hemodialysis; 

history of accidents or unpleasant events over the 

past 6 months; kidney transplant or PD; death

Depression diagnosis: Any

BDI-II-II: no description of 

application, but did say that 

patients’ depression had to be 

confirmed by a neurologist

BDI-II: 

32.46±9.86 vs 

30.58±9.24

Kalani, 201971

Acupressure

N = 96

Iran, 2011

3 sites: HD centers

44% Female

Age: 53.4±13.9

Race: NR

Education: 31% nonliterate

Employment: 50% 

Unemployed; 41% 

retired

Insurance: NR

Included: ESRD diagnosis; Age 18+; HD for ≥3 

months; BDI-II score ≥10; mental and 

psychological ability to participate 

Excluded: wounds or fractures at acupressure 

points; used complementary medicine in last 3

months; lower extremity amputation; unstable 

physiological symptoms; high creatinine and high 

urea; acute mental and psychological problems for 

the past 6 months

Depression diagnosis: Any

BDI-II: pts fill before and after 

intervention

BDI-II: Tx 27.5 

± 9.1 vs PBO 

25.7 ± 7.7 vs C 

24.6 ± 8.6 (not 

sig diff)

Kouidi, 201074

Exercise 

training

N = 50

Greece, year 

NR

Single site: hospital 

renal unit

HD: 3x/wk for 4 hrs

41.6% Female

Age: 46.3 ± 11.2

Education: 10.2 ± 3.4 

yrs

Employment: 16.6% 

Unemployed

Race/Insurance: NR

Included: ESRD; 4 hrs HD 3x/wk for ≥6 months

Excluded: history, clinical signs, or symptoms of 

psychiatric, neurological, cardiologic, or pulmonary 

disorders; diabetes mellitus; significant electrolytic 

instability or undisciplined patients; 

musculoskeletal limitation or other medical 

problems contraindicating participation in an ET 

program

Depression diagnosis: NR (mild-severe)

BDI-II and HADS: 

administered to

all patients at the beginning 

and at the end of the study by 

the same physician, who was 

not familiar with the

patients

BDI-II: 22.29 ± 

6.71 vs 22.30 ± 

6.81

HADS: 10.63 ± 

2.60 vs 10.40 ± 

2.50
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Lerma, 201770

CBT

N = 60

Mexico City, 

MX Year NR

2 sites: HD units

HD: 3x/wk for 3-4hrs

51.6% Female

Age: 41.8 ± 14.7

Education: 35.5% 

elementary

Employment: 25.8% 

Unemployed

Race/Insurance: NR

Included: ESRD; mild-moderate depression; 

literate; no psychiatric illness; regular attendance 

of HD sessions 3-4 hrs HD 3x/wk for ≥6 months

Excluded: BDI-II > 29 points were referred for 

appropriate psychiatric evaluation and care.

Depression diagnosis: mild-moderate (BDI-II score 

of 10–29 points)

BDI-II: questionnaires 

completed in privacy with 

supervision of a trained 

technician

BDI-II: 13.6 ± 

7.6 vs 15.8 ± 

10.0

Rahimipour, 

201576

Hope therapy

N = 50

Iran, year NR

Multi-site: hospitals

HD: 2-3x/wk for 4 hrs

48% Female

Age: 47.82 (15.12)

Race/Education/Employ

ment/ Insurance: NR

Included: 18–65 y/o; HD 2-3x/wk for ≥3 months; 

not taken medication for depression, anxiety, or 

stress

Excluded: NR

Depression diagnosis: NR

DASS-21 questionnaire;

application details NR

DASS-21:13.3

6 ± 3 vs 13.64 

± 3.5; No 

difference (t = 

0.3; P = 0.76) 

Thomas, 

201778

MBSR

N = 41

Montreal, 

Canada, 2016

Single site: hospital HD 

unit

33% Female

Age: 65 ± 13

Race: 49% white, 51% 

nonwhite

Education: 63% ≤ high 

school 

Employment/Insurance: 

NR

Included: On maintenance HD; spoke English or 

French; had depression (PHQ-9 score ≥6) and/or 

anxiety symptoms (GAD-7 score ≥6)

Excluded: sig cog impairment; psychosis; suicidal 

ideation/intent

Depression diagnosis: Any

PHQ-9: Participants 

completed questionnaires with 

an independent assessor

PHQ-9: 12.7 ± 

4.2 vs 11.9 ± 

5.8
ESRD and Depression Evidence Synthesis Program

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Author, Year

Intervention, 

N enrolled

Country/US 

region, years 

of enrollment

Study setting,

clinical 

characteristics, 

demographics Inclusion Criteria/ Depression Diagnosis 

Depression Screening 

Tool(s) and their application

Baseline 

Depression 

Score 

Mean ± SD, T 

vs C

Tsay, 200472

Acupressure

N = 108

Northern 

Taiwan, Year 

NR

4 sites: hospital dialysis 

centers

Duration HD: 50.06 

(44.15) months

66% Female

Age: 58.16 (12.19)

Employment: 76.1% 

Retired or Unemployed 

Race/Education: NR

Included: ESRD diagnosis; Age 18+; HD for ≥3 

months; fatigue; PSQI score ≥5; BDI-II score ≥10

Excluded: lower-extremity amputations, comorbid 

psychiatric disorders, congestive heart failure, 

COPD, insulin-dependent diabetes, neuromuscular 

disease, systemic lupus erythematosus, 

rheumatoid arthritis, cancer, regular steroid 

therapy, or use of anti-hypertension medications.

Depression diagnosis: Any

BDI-II; application details NR BDI-II:

Acupressure 

20.37±10.65 vs 

TEAS 18.20 ± 

11.11 vs C 

21.61 ± 11.69 

Widyaningrum, 

201377

Latihan Pasrah 

Diri

N = 36

Java, 

Indonesia, 

2012

Single site: hospital HD 

unit

HD: 2x/wk

61.1 % Female

Age: 50.06 (7.39)

Education: 77.8% ≤ high 

school

Insurance: 5.6% 

uninsured 

Employment/Race: NR

Included: CKD patients on 2x/wk HD for ≥3 

months; BDI-II ≥16, 18-60 y/o

Excluded: taking antidepressant or psychotropic 

meds, undergoing psychotherapy, or unable to do 

relaxation exercises

Depression diagnosis: Any

BDI-II; application details NR BDI-II: 23 ± 

5.34 vs 23.39 ± 

5.02

Abbreviations: BDI-II = Beck Depression Inventory-II; CKD = chronic kidney disease; COPD = Chronic Obstructive Pulmonary Disease; DASS = Depression, 

Anxiety, and Stress Scale; DM = diabetes mellitus; DSM-IV = Diagnostic and Statistical Manual-IV; ESRD = end-stage renal disease; ET = Exercise training; 

GAD = Generalized Anxiety Disorder; HADS = Hospital Anxiety and Depression Scale; Ham-D =Hamilton Depression Rating Scale; HD = hemodialysis;

MADRS = Montgomery–Åsberg Depression Rating Scale; MAOI = Monoamine oxidase inhibitors; MDD = Major Depressive Disorder; MINI = Mini 

International Neuropsychiatric Interview; MMSE = Mini-Mental Status Examination; MX = Mexico; NM = New Mexico; NR = not reported; NY = New York; 

P = p-value; PD = peritoneal dialysis; PHQ-9 = Patient Health Questionnaire-9; PSE = psychoeducation; PSQI = Pittsburgh Sleep Quality Index; QIDS-C = 

Quick Inventory of Depressive Symptomatology - Clinician; SD = standard deviation; SERT = Sertraline RCT = randomized controlled trial; TEAS =

Transcutaneous Electrical Acupoint Stimulation; TX = Texas; US = United States; WA = Washington; wk = week
ESRD and Depression Evidence Synthesis Program

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Table 8. Efficacy of interventions for depression in ESRD patients from randomized controlled trials

Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

PHARMACOLOGICAL

SSRIs vs control

Blumenfield, 

199760

N = 14

Fluoxetine vs 

placebo

7 vs 7

Tx = 8 weeks

F/U = 8 weeks

Fluoxetine: 20mg/day 

for 8 weeks

Matched placebo No difference between 

groups at 8 wks. FLU sig 

better than PBO at 4 weeks

on BDI, BSI, and electronic 

VAS, but not other scales. 

HAM-D only reported end of 

study difference: not 

significant.

Mean change from baseline 

(at 4 wks; at 8 wks):

BDI: -12 vs -4.17 (P = 0.05); 

-9.57 vs -8.8 (P = 0.91).

BSI: -6.29 vs 0.2 (P = 0.04); -

4.43 vs -3.2 P = 0.88

HAM-D: no 4 wk 

assessment; -9.00 vs -7.5 (P 

= 0.72) 

MADRS: -7.20 vs -6.75 (P = 

0.93); -11.14 vs -6.67 (P = 

0.45)

VAS: -210.0 vs -58.3 (P = 

0.37); -303.0 vs -140 (P = 

0.45) 

Electronic VAS: -262.4 vs 5.6 

(P = .05); -389.0 vs -87.8 (P 

= 0.13)

NA Poor

Friedli, 201761

Sertraline vs 

placebo

Sertraline: 100mg/day

(50mg/day to start. 

Dose could be 

Matched placebo No treatment effect

MADRS between group 

difference at 6 months: 

NA Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

15 vs 15

Tx = 6months

F/U = 6months

increased to max at 2 

and 4 months) 

-0.67 (-5.7 to 4.4); NS

Within groups decrease 

significant for both groups

Mean change at study end

MADRS: -14.5 (95% CI: -

20.2 to -8.8) vs -14.9 (95% 

CI: -18.4 to -11.5) 

BDI-II: -15.7 (95% CI: -24.3 

to -7.1) vs -13.0 (95% CI: 

19.6 to -6.4); between groups 

diff NS

Taraz, 201362

Sertraline vs 

placebo

25 vs 25

Tx = 12 weeks

F/U = 12 weeks

Sertraline: 100mg/day

(50mg/day for 1st 2 

weeks) 

Matched placebo Favors SERT

BDI-II scores (Baseline, 6 

weeks, 12 weeks, Baseline 

to 12 weeks): Sertraline: 29 

(13); 21 (11.5); 15 (5.5); 

−11.3±5.8 vs Placebo: 23 

(11); 22.5 (8.5); 22.5 (9); 

−0.5±5, Comparison baseline 

to 12 weeks between groups 

(P = 0.001).

NA Fair

SSRIs vs active comparator

Hosseini, 201264

Head-to-head

Citalopram vs 

psychological 

training

22 vs 22

Tx = 3 months

F/U = 3 months

Citalopram: 20mg/day Psychological training: 6 1-

hr sessions explaining 

kidney anatomy; 

physiopathology and 

causes of kidney failure; 

treatment modalities with 

their dis/advantages; HD 

mechanisms; required care 

for HD patients; stages of 

adaptive reaction; problem 

solving, stress 

Post-intervention HADS: 6.26 

± 4.18 (P = 0.001) vs 7.33 ± 

4.80 after training (P = 0.04). 

No difference between 

groups (P = 0.16). 

Between groups mean 

differences also NS (P =

0.65)

NA Poor
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

management, and muscle 

relaxation techniques.

Mehrotra, 201963

Head-to-head

Sertraline vs CBT

60 vs 60

Tx = 12 weeks

F/U = 12 weeks

Sertraline: 200mg/day 

unless limited by AEs 

(titration began at 25 

mg/d and adjusted each 

visit)

CBT: 10 60-minute 

sessions during HD for 12 

weeks. 

Therapy included standard 

components of the 

intervention 

(psychoeducation, 

behavioral intervention, 

cognitive intervention, and 

health behavior 

modification) adapted for 

maintenance hemodialysis 

(adherence to dialysis and 

challenging disease-specific 

cognitive distortions and 

maladaptive thought 

patterns)

Sertraline more effective than 

CBT for physician reported, 

but not self-reported, 

depression after sensitivity 

analyses with multiple 

imputation.

QIDS-C scores: 5.9 ± 4.5 vs 

8.1 ±5.1

Effect estimate: −1.85 (95% 

CI: −3.55 to −0.16)

BDI-II scores: 14.1 (95% CI:

11.2 to 17.0) vs 18.7 (95% 

CI: 15.2 to 22.2.

Effect estimate: −2.9 (95% 

CI: −6.7 to 0.8)

NA Fair

Supplements

Gharekhani, 

201466

Omega-3 fatty 

acid vs placebo

27 vs 27

Tx = 4 months

F/U = 4 months

Omega-3 fatty acids: 

1,800 mg/day (as 6 softgel capsules, each

containing 180 mg EPA 

and 120 mg DHA, 2 

capsules taken 3x/day) 

for 4 months

Matched placebo: Paraffin 

oil capsules

Favors Omega-3

Mean end of study BDI-II: 

13.44 ± 5.66 vs 20.33 ± 7.56. 

Diff: −10.08 ± 8.07 vs −0.88

± 8.41; P = 0.001

Within groups: Sig decrease 

(P < 0.001) vs ND

NA Poor

Wang, 201665

Vitamin D3 vs 

placebo

373 vs 373

High-dose Oral Vitamin 

D3: 52-week treatment 

of 50,000 IU/wk. 

Treatment time 7-9:00 

PM.

Matched placebo No between groups 

difference in delta values.

Within group BDI-II scores 

baseline to end of study: 22.7 

± 4.3 to 19.6 ± 3.7; P = 0.021 

NA Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

Tx = 52 weeks

F/U = 52 weeks

vs 21.9 ± 5.4 to 20.8 ± 5.1; P

= 0.033

NON-PHARMACOLOGICAL

Al Saraireh, 

201868

CBT vs PSE 

(head-to-head)

65 vs 65

Tx = 12 weeks

F/U = 12 weeks

CBT: 7 individual 1-hr 

sessions following the 

traditional CBT sessions 

protocol

Psychoeducation (PSE): 7 

individual 1-hr sessions. 

The intention of 

psychoeducation is to 

educate people about their 

disease, its treatment, and 

rehabilitation. Moreover, 

this technique should 

promote acceptance of the 

disease, active participation 

of the patient in the 

treatment process, and 

learning different strategies 

to deal with the problems 

caused by the disease.

Both groups experienced 

significant decrease in 

depression scores. 

Post-test HAM-D scores: 

15.0 (5.5) vs 11.1 (2.3). 

Between groups depression 

scores favored PSE (t = 4.68; 

P < 0.01) over CBT.

NA Poor

Babamohamadi, 

201779

Quran vs TAU

30 vs 30

Tx = 1 mo

F/U = 1 mo

Quran: Listen to audio 

of Quran recitation on 

headphones for 20 

minutes, beginning 5 

minutes before dialysis

TAU Favors Quran. 

Post-test BDI-II scores: 14.5 

± 4.8 vs 31.6 ± 9.2; P < 

0.0001.

Significant between-subjects 

treatment effect, independent 

of age (F = 9.3, P = 0.004,

Cohen’s d = 0.85).

NA Poor
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

Beizaee, 201875

GI vs TAU

40 vs 40

Tx = 4 weeks

F/U = 4 weeks

Guided Imagery:

3x/wk for 4 weeks

administered by certified 

psychologist

30 mins prior to HD 

session

Audio recording of 

nature sounds. Told to 

breathe, relax, and 

imagine they are in the 

place with the sounds 

(ie, waterfall, sea 

waves, jungle, etc)

TAU, nearly silent 

environment

Post-test HADS scores: 

10.02 ± 2.58 vs 11.65 ± 2.33

SBP: Mean Before 129.22 

± 12.70 vs 132.85 ± 

13.22; After 121.75 ± 

12.73 vs 134.87 ± 12.68

DBP: Before 82.50 ± 

11.32 vs 81.75 ± 8.51; 

After 81.00 ± 10.32 vs 

81.87 ± 8. 14

HR: Before 77. 95 ± 6. 97 

vs 75. 42 ± 8.56; After 

73.75 ± 6.25 vs 77.22 ± 

7.92

Fair

Cukor, 201469

CBT vs waitlist 

(crossover)

38 vs 27

Tx = 3 months

F/U = 6 months

CBT: Individual 60min 

CBT chairside during 

dialysis

CBT modified for pop.

10 sessions over 3

months

Wait-list control Favors tx first compared to 

wait list. Mean change score 

during treatment was -11.7 

points (SD 1.5; P,0.001) (raw 

mean change from 24.7 [SD 

9.8] to 11.7 [SD 9.8]) among 

those receiving treatment 

first, and -4.8 points (SD 1.4; 

P < 0.001) for those receiving 

treatment after completing 

the waitlist (raw mean 

change from 14.5 [SD 8.5] to 

9.1 [SD 6.5]) There was also 

significant mean change in 

BDI-II score in the untreated 

group during the waitlist 

period (-6.7 points [SD 1.7]; 

P < 0.001) (raw mean 

change from 21.9 [SD 8.9] to 

QOL: favors tx, 

irrespective of when it 

occurs. Treatment effect = 

+12.0 points (SD 3.4; P = 

0.003) (raw mean score 

change from 99.5

[SD 27.9] to 115.3 [SD 

25.5]) for tx first vs +11.3 

points (SD 3.7; P = 0.01) 

(raw mean change from 

110.6 [SD 25.1] to 119.7 

[SD 24.7]) for those 

treated after waitlist. 

Between group difference 

in mean change score sig 

P = 0.04

Significant increase in 

QOL associated with 

treatment, but not waitlist. 

P = 0.04.

Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

14.5 [SD 8.5]).

BDI-II: The magnitude of 

BDI-II improvement was 

significantly greater in the 

intervention group than it was 

in patients in the intervention 

waitlist condition (P = 0.03)

HAM-D: The difference in 

mean change score between 

treated and untreated groups 

was highly significant (P < 

0.001).

SCID-I: Between groups not 

reported

Fluid Adherence: favors tx

irrespective of when it 

occurs: model-estimated 

mean change score 

during treatment -

1.3%Δkg/d (SD 0.3; P = 

0.001) (raw mean change 

from 4.0 [SD 2.0] to 2.8 

[SD 1.6]) for tx first and -

1.1%Δkg/d (SD 0.3; P = 

0.001) (raw mean change 

from 3.6 [SD 2.0] to 2.5

[SD 2.0]) among waitlist 

first. difference between tx 

groups and control sig P = 

0.002

Duarte, 200967

CBT vs 

psychotherapy

46 vs 44

Tx= 12 weeks

F/U = 9 months

CBT: Group CBT 

sessions (with 

psychologist specialized 

in CBT)

90 minutes 1x/wk for 12 

weeks; Pts not on HD 

during sessions; 

Structured, manualized 

methodology; Followed 

by 6 months 

maintenance w/ monthly 

mtgs

Individualized 

psychotherapy with 

psychologist (routinely 

available in dialysis unit) 

30-50 min 1x/wk for 12 

weeks;

Followed by as-needed 

psychological care for 6

months

Both groups experienced 

improvement on BDI-II and 

MINI (P < 0.001), but T’s 

improvement was greater.

BDI-II: After 3 months 14.1 ±

8.7 vs 21.2 ± 9.1 (P = 0.001); 

After 9 months 10.8 ± 8.8 vs 

17.6 ± 11.2 (P = 0.002) 

MINI: the mean change from 

baseline ± SE favored 

intervention. 

After 3 months: 4.5 ± 0.4 vs 

2.1 ± 0.6; P < 0.001

After 9 months: 4.4 ± 0.4 vs 

2.9 ± 0.5; P = 0.031 

Suicide Risk Module 

(MINI): No between 

groups difference. 

Baseline 2.2 ± 5.1 vs 1.4

± 3.5, P = 0.287; After 3 

months 1.2 ± 4.2 vs 0.7 ±

1.9, P = 0.433

After 9 months 0.6 ± 1.2 

vs 0.6 ± 2.0, P = 0.947

Overall reduction, within 

group comparison:

Significant reduction 

within T group (P = 0.007)

vs C (P = 0.130)

QOL: CBT group 

significantly improved 

several dimensions of 

Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

KDQOL. Between groups 

sig improvement in 

burden of kidney disease, 

quality of social 

interaction, sleep, overall 

health, and mental 

component summary 

dimensions.

Heshmatifar, 

201573

BRT vs TAU

35 vs 34

Tx = 1 month

F/U = 1 month

Benson relaxation 

technique (BRT): Pts 

attend training sessions, 

then demonstrate 

technique to researcher 

during each of their HD 

sessions. The rest of the 

practices were done 

without supervision 

using a pamphlet and 

CD. Performed 20 

minutes 2x/day for 1 

month.

TAU Only T group’s scores 

decreased. The difference 

between groups was 

significant (P = 0.01).

NA Poor

Kalani, 201971

Acupressure vs 

Sham vs TAU

32 vs 32 vs 32

Tx = 4 weeks

F/U = 4 weeks

Acupressure: Applied 

during 1st 2hrs of HD. 

3x/wk for 4 weeks. to 

both the legs, both the 

arms, and the back. the 

main acupressure points 

included SP6, ST36 

GB34, K1, BL23 and 

HT7. Each session 

lasted 20 minutes; 2 

minutes for the primary 

surface stroke to relax 

Sham: Same as 

acupressure group except 

pressure applied 1cm from 

actual acupressure points.

Control: TAU

Post-test: Tx 20.6 vs PBO 

25.5 vs C 24.9 significant 

difference between T and 

other groups (P = 0.001 for 

both); No difference between 

PBO and C (P = 0.220).

NA Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

the solidity and the 

remaining 18 minutes 

for pressing the 6 points 

(3 minutes for each 

point). average of 3–4 

kg pressure

Kouidi, 201074

ET vs control

25 vs 25

Tx = 1 year

F/U = 1 year

Exercise Training (ET) 

program:

3x/wk 60-90 min. during 

1st 2 hrs of HD session 

physician and trainer 

supervised

sessions: warm-up, 

cycling, strengthening, 

and cool-down

Sedentary control Favors ET in both BDI-II and 

HADS scores (P < 0.001)

Heart rate variability

(HRV) Indices: SDNN, 

MSSD, pNN50, LF, HF, 

and LF/HF all significantly 

increased in exercise 

group, but not controls. 

After intervention exercise 

group was significantly 

better in all variables P < 

0.001

Poor

Lerma, 201770

CBT vs waitlist

38 vs 22

Tx = 5 wks

F/U = 9 wks

CBT: 5, group Cognitive 

Behavioral Intervention 

sessions (2hrs)

1x/wk after HD session

3 techniques: 1. 

Behavioral activation; 2. 

Deep breathing and 

muscle relaxation; 3. 

Cognitive restructuring

Wait list BDI-II after 5 weeks (end of 

intervention): 10.2 ± 8.2 vs 

15.0 ± 10.9; P = 0.084 

BDI-II after 9 weeks (followup): 7.1 ± 7.2 vs 14.7 ± 9.7; 

P = 0.003. 

Significant overall within 

group reduction in scores for 

tx (<0.001), but not controls 

(0.866). 

Between groups RR of 

reducing depressive 

symptoms = 1.7 

Adjusted RR between

groups for depression = 0.33 

(33% clinical utility, 95% CI: 

0.05 to 0.55)

Overall QOL (by PLC) 

favors treatment: 

Baseline: 99.4 ± 21.3 vs 

91.5 ± 19.5; P = 0.203; 

After 5 weeks:109.6 ± 

21.1† vs 94.0 ± 21.0; P =

0.016

After 9 weeks: 112.5 ± 

23.8 vs 91.3 ± 22.5; P =

0.004

Overall within group P =

0.001 vs P = 0.663. 

Cohen's d = 0.93 (large)

Fair
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

Rahimipour, 

201576

Hope therapy vs 

control

25 vs 25

Tx = 8 weeks

F/U =12 weeks

Hope therapy: Sessions 

utilizing Schneider’s

hope therapy theory

1x/wk for 8 weeks

1-1.5 hr during 1st 2hrs 

of dialysis administered 

by researcher

Control: Listening session 

with researcher’s coworker 

in which pts could talk 

about their disease and 

problems

1x/wk for 8 weeks

Immediately after 8wkintervention (t = 12.75; P <

0.001), and at 1-month 

follow-up (t = 13.83; P <

0.001)

NA Poor

Thomas, 201778

MBSR + 

psychoed vs TAU 

+ psychoed

21 vs 20

Tx = 8 weeks

F/U = 8 weeks

MBSR: guided, 

chairside meditative 

practices 

10–15 minutes

3x/wk during 

hemodialysis sessions

4 meditation techniques 

drawn from 

mindfulness-based 

cognitive therapy (body 

scan, guided meditation, 

silent

meditation, and gentle 

arm movements)

Both control and 

intervention

groups received 

psychoeducational 

literature on anxiety and 

depression.

TAU. Both control and 

intervention groups 

received psychoeducational 

literature on anxiety and 

depression.

No significant change in 

PHQ-9: -3.0±3.9 vs 2.0±4.7; 

P = 0.45

NA Fair

Tsay, 200472

Acupressure vs 

TEAS vs control 

36 vs 36 vs 36

Tx = 4 weeks

F/U = 4 weeks

Acupressure: applied for 

15min 3x/wk for 4 

weeks

3 min massage, then 4 

acupoints (specific 

points in paper) treated 

Control group (not 

described)

Acupressure and TEAS are 

similarly effective, and 

significantly more effective 

than no intervention (P = 

0.009 and P = 0.008 

respectively). No difference 

Fatigue (by PFS): 

Baseline Acu 5.92 ± 1.39 

vs TEAS 5.60 ± 1.30 vs C 

6.01 ± 1.60; Follow-up 

Acu 4.61 ± 1.72 vs TEAS 

4.70 ± 1.50 vs C 5.70 ± 

Poor
ESRD and Depression Evidence Synthesis Program

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Author, Year

N randomized 

(T vs C), 

Duration of 

treatment and 

follow-up

Intervention 

description Comparator description 

Findings, Treatment vs Comparator

Depression Other outcomes Quality

for 3 min each with 

finger force 3-4kg by 

investigators and RAs 

who had received 

training from Chinese 

medicine physician vs 

Transcutaneous 

Electrical Acupoint 

Stimulation (TEAS):

applied for 15min 3x/wk 

for 4 weeks

3 min massage, then 4 

acupoints (specific 

points in paper) treated 

for 3 min each with 

2hz/100hz alternating 

every 3 seconds applied 

with paired skin 

electrodes on acupoints

between acupressure and 

TEAS (P = 0.95)

1.80. Post-hoc analysis 

found significantly lower 

levels in Acu (P = 0.006) 

and TEAS (P = 0.02) 

when compared with 

controls. No difference 

between Acu and TEAS

Sleep quality (by PSQI): 

Baseline Acu 8.85 ± 4.50 

vs TEAS 7.12 ± 4.51 vs C 

9.35 ± 3.48; Follow-up 

Acu 7.80 ± 4.00 vs TEAS 

6.32 ± 4.55 vs C 9.75 ± 

4.65. Compared to 

controls significantly 

better with Acu (P = 0.05) 

and TEAS (P = 0.016). No 

difference between Acu 

and TEAS

Widyaningrum, 

201377

LPD vs control

18 vs 18

Tx= 3 weeks

F/U= 3 weeks

Latihan pasrah diri 

(LPD): method 

combining relaxation 

and remembrance by 

focusing practice on 

breathing and words in 

the dhikr (relaxation and 

repetitive prayer) for 

evoking relaxation 

response.

2x/ day for 21 days

Control group (not 

described)

Significantly decreased BDIII scores within both groups, 

and greater in LPD, but 

between group difference not 

significant (P = 0.201)

QOL (by KDQOL-SF36): 

significantly greater prepost change associated 

with LPD vs control in 

sleep and overall health. 

No other differences were 

significant.

Poor

Note. See Appendix D for details regarding quality assessment. 
ESRD and Depression Evidence Synthesis Program

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Abbreviations: AE = adverse event; BDI-II = Beck Depression Inventory; BRT = Benson relaxation technique; BSI = ; CBT = Cognitive Behavioral Therapy; 

CKD = chronic kidney disease; DASS = Depression, Anxiety, and Stress Scale; DBP = diastolic blood pressure; DSM = Diagnostic and Statistical Manual of 

Mental Disorders; ESRD = end-stage renal disease; ET = exercise training; FLU = fluoxetine; HADS = Hospital Anxiety and Depression Scale; HAM-D = 

Hamilton Depression Rating Scale; HD = hemodialysis; HR = heart rate; HRV = heart rate variability; KDQOL-SF = Kidney Disease Quality of Life Short 

Form; LPD = Latihan Pasrah Diri; MBSR = mindfulness-based stress reduction; MINI = Mini International Neuropsychiatric Interview; NR = not reported; NS = 

not significant; P = p-value; PBO = placebo; PD = peritoneal dialysis; PFS = Piper Fatigue Scale; PSE = psychoeducation; PHQ = Patient Health Questionnaire;

PLC = Profile of Quality of Life in the Chronically Ill; PSQI = Pittsburgh Sleep Quality Index; QIDS-C = Quick Inventory of Depressive Symptomatology - 

Clinician; QOL = quality of life; RR = relative risk; RCT = randomized controlled trial; SCID-I = The Structured Clinical Interview for DSM-IV Axis I 

Disorders; SERT = sertraline; SPB = systolic blood pressure; SSRI = Selective serotonin reuptake inhibitor; TAU = treatment as usual; TEAS = Transcutaneous 

Electrical Acupoint Stimulation
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Table 9. Summary of the evidence on interventions for depression in patients with ESRD

Outcome Conclusion Strength of Evidence 

(Justification)*

SSRIs vs controls (k = 3, n = 94)

Depression severity

Fluoxetine60

No benefit (k = 1, n = 14)

Sertraline61,62

Mixed findings (k = 2; n = 80)

Insufficient (NC, SLM) 

SSRIs vs active comparator (k = 2; n = 164)

Depression severity

Sertraline vs CBT63

Benefit for both; no difference between groups (k = 1, n = 120) Low (SLM, UC)

Citalopram vs psychological training64

Benefit for both; no difference between groups (k = 1, n = 44) Insufficient (SLH, UC) 

Supplements vs placebo (k = 2; n = 800)

Depression severity

Omega-3 Fatty Acids66

Increased benefit (k = 1, n = 54) Insufficient (NP, SLH, UC)

High-dose Vitamin D365

No benefit (k = 1, n = 746) Moderate (SLM, UD, UC)

CBT vs active comparator (k = 2; n = 220)

Depression severity

CBT vs psychoeducation68

Benefit for both, but favored psychoeducation (k = 1, n = 130) Insufficient (SLH, UC)

CBT vs psychotherapy67

Benefit for both, but favored CBT (k = 1, n = 90) Low (SLM, UC)

Suicide risk

CBT vs psychotherapy67

Benefit in intervention but not control group; no difference between groups 

(k = 1, n = 90)

Low (SLM, UC)

QOL CBT vs psychotherapy67

Increased benefit for some domains of KDQOL (k = 1, n = 90) Low (SLM, UC)

CBT vs control (k = 2; n = 125)69,70

Depression severity Increased benefit (k = 2; n = 125) Low (SLM)

QOL Increased benefit (k = 2; n = 125) Low (SLM)

Fluid Adherence Increased benefit (k = 1; n = 65)69 Insufficient (SLM, UC)
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Outcome Conclusion Strength of Evidence 

(Justification)*

Acupressure vs control (k = 2; n = 204)

Depression severitya 

Acupressure vs TAU71,72

Increased benefit (k = 2; n = 204)

Acupressure vs sham71

Increased benefit (k = 1; n = 96)

Low (SLM) 

Fatigue Acupressure vs TAU72

Increased benefit (k = 1, n = 108) Insufficient (SLH, UC) 

Sleep quality Acupressure vs TAU72

Increased benefit (k = 1, n = 108) Insufficient (SLH, UC) 

Acupressure vs active comparator (k = 1, n = 108)

Depression severity Acupressure vs TEAS72

Benefit for both; no difference between groups Insufficient (SLH, UC) 

Fatigue Acupressure vs TEAS72

Benefit for both; no difference between groups Insufficient (SLH, UC) 

Sleep quality Acupressure vs TEAS72

Benefit for both; no difference between groups Insufficient (SLH, UC) 

Benson Relaxation Technique vs control (k = 1; n = 70)73

Depression severity Increased benefit Insufficient (SLH, UC)

Exercise training vs control (k = 1; n = 50)74

Depression severity Increased benefit Insufficient (SLH, UC, UP)

HRV Increased benefit Insufficient (SLH, UC, UP)

Guided Imagery vs TAU (k = 1; n = 80)75

Depression severity Unclear effect Insufficient (SLM, UC)

Vital signs Unclear effect Insufficient (SLM, UC)

Hope therapy vs active control (k = 1; n = 50)76

Depression severity Increased benefit Insufficient (SLH, UC, UP)

LPD vs control (k = 1; n = 36)77

Depression severity No benefit Insufficient (SLH, UP, UC)

QOL No benefit Insufficient (SLH, UP, UC)

MBSR vs TAU (k = 1; n = 41)78

Depression severity No benefits Insufficient (SLM, UP, UC)
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Outcome Conclusion Strength of Evidence 

(Justification)*

Quran vs TAU (k = 1; n = 60)79

Depression severity Increased benefit Insufficient (SLH, UC, UP) a

Some participants are represented more than once

*The overall quality of evidence for each outcome is based on the consistency, coherence, and applicability of the body of evidence, as well as the internal 

validity of individual studies. The strength of evidence is classified as follows:29

High = Further research is very unlikely to change our confidence on the estimate of effect.

Moderate = Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low = Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Insufficient = Any estimate of effect is very uncertain.

Abbreviations: CBT = cognitive behavioral therapy; HRV = heartrate variability; k = number of studies; LPD = Latihan Pasrah Diri; MBSR = mindfulness-based 

stress reduction; n = sample size; NC = not consistent; ND = not direct; NP = not precise; SLH = study limitations high; SLM = study limitations medium; SSRI 

= Selective Serotonin Reuptake Inhibitor; TAU = treatment as usual; UC = unknown consistency; TEAS = Transcutaneous Electrical Acupoint Stimulation; UD 

= unclear directness; UP = unclear precision
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Table 10. Ongoing randomized controlled trials of depression treatments in patients with ESRD

PI/Study Director 

(Registration);

Study Design; Sponsors; 

Estimated Study 

Completion

Study Title Purpose of Study Participants; Intervention(s)/

Comparator 

Outcomes and 

Timing

Looper, K (NCT02686333)

• RCT

• Sponsored by the Lady 

Davis Institute, Jewish 

General Hospital, 

Montreal, Canada

• June 2019

Meditation Intervention for 

the Treatment of 

Depression and Anxiety 

Symptoms in Patients 

Undergoing Dialysis: A 

Randomized Control Trial

Examine the use of 

brief meditation 

interventions for 

patients with 

symptoms of anxiety 

and depression who 

are undergoing 

dialysis

50 Patients on maintenance 

hemodialysis with anxiety and 

depression

10-15 minutes of individually 

conducted medication practices 

(silent meditations, guided 

meditations, body scans, gentle arm 

movement exercises) vs mental 

health lit. and TAU

Secondary: Change in 

PHQ-9 after 8 weeks

Rej, S

(NCT03406845) 

• Head-to-head RCT

• Sponsored by the Lady 

Davis Institute, Jewish 

General Hospital, 

Montreal, Canada

• June, 2019

Brief Chair-Side 

Mindfulness Intervention for 

Depression and Anxiety 

Symptoms in Patients 

Undergoing Dialysis: A Pilot 

Randomized Control Trial 

with an Active Control 

Group

Examine the 

acceptability of 

meditation Examine 

techniques versus 

health promotion in 

people receiving 

dialysis who have 

anxiety or depression

60 adult patients on maintenance 

HD with depression and/or anxiety

Tailored, chair-side mindfulness 

intervention based on Mindfulnessbased Cognitive Therapy (MBCT) vs 

group health promotion based on 

the Health Enhancement Program 

(HEP) as active control for 8 weeks

PHQ-9 depression 

scores at 8 weeks and 

6 months follow-up

Other outcomes: 

sleep, QOL, perceived 

stress and 

improvement, social 

difficulties, HRV, 

ESAS

Khatami, SMR

(IRCT201201175113N2)

• Single-blind RCT

• Nephrology Research 

Center, Tehran 

University of

Medical Sciences, Iran

• Started 2012, end NR

A Clinical Trial Comparing 

the Effect of Omega-3 with 

Sertraline and

Placebo on Depression 

General Health Conditions 

Among Dialysis

Patients

Compare the efficacy 

of Omega-3 and 

Sertraline for 

depression in ESRD 

patients

75 adult HD patients with 

depression

Omega-3 1500mg vs Sertraline 50-

150mg vs placebo for 3 months

HADS at 4, 8, and 12 

weeks

Abbreviations: ESAS = Edmonton Symptom Assessment Scale; ESRD = end-stage renal disease; HADS = Hospital Anxiety and Depression scale; HD = 

hemodialysis; HRV = heartrate variability; NR = not reported; PHQ = Patient Health Questionnaire; QOL = quality of life; RCT = randomized controlled trial; 

TAU = treatment as usual
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KEY QUESTION 4: In patients with ESRD and depression, what are the 

potential harms of screening and treatment?

Five pharmacological trials reported adverse events. Sertraline trials most commonly reported 

AEs. Some harm outcomes were more common with Sertraline than placebo including study 

dropouts due to AEs, nausea, and other nonserious AEs, but none of these were more severe than 

for the general population. There were also some dropouts due to AEs in the trial of high-dose 

Vitamin D3. There were no serious AEs in the non-pharmacological trials.

A. Screening

No included studies reported on harms of screening.

B. Treatment

Summary of Findings

Five pharmacological trials reported adverse events (AEs). Sertraline trials most commonly 

reported AEs. Some harm outcomes were more common with Sertraline than placebo including 

study dropouts due to AEs, nausea, and other nonserious AEs, but none of these were more 

severe than for the general population. There were also some dropouts due to AEs in the trial of 

high-dose Vitamin D3. There were no serious AEs in the non-pharmacological trials.

Pharmacological

SSRIs 

A wide range of AEs were reported by participants in both the treatment and control groups in 4 

trials examining SSRIs. Across trials, AEs were not consistently reported. The following AEs 

were reported in 2 or more trials: nausea, infections, headaches, dizziness or hypotension, 

gastrointestinal issues, sexual dysfunction, and insomnia. Three of 4 trials reported nausea as a 

common AE.60-62 Other reported AEs included major bleeding, cardiac and nervous system 

conditions.63 Three sertraline trials performed analyses of adverse events between groups. One 

trial reported significantly more study dropouts due to adverse or serious adverse events 

associated with sertraline (33% vs 0%; P = 0.04).61 A second trial reported no difference in the

frequency of adverse events, with the exception of more frequent reports of nausea associated 

with sertraline (P = 0.033).62 In the third trial, there were no significant differences between 

SAEs associated with sertraline and CBT (RD = 0.08; 95% CI: −0.11 to 0.28). However, there 

were more nonserious AEs associated with sertraline (RD = 0.65: 95% CI: 0.25 to 1.05).63 Only 

the trial of citalopram included no reported SAEs.64 Overall, AEs for SSRIs in ESRD patients 

with depression were no more severe than reported by the general population treated with SSRIs. 

There is no evidence that SSRIs are more harmful for this population. 

Supplements 

No serious AEs associated with omega-3 fatty acids were reported.

66 Adverse events associated 

with high dose vitamin D3, including joint pain, diarrhea, nausea, and vomiting resulted in study 

withdrawal of 5 participants.

65 No statistical analyses were performed, and the evidence is 

insufficient to form conclusions. 
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Non-pharmacological

Four trials of non-pharmacological interventions reported on adverse events. No adverse events 

were reported in trials of Latihan Pasrah Diri,77 MBSR,78 and exercise training.

74 One CBT trial 

reported no discontinuations due to serious adverse events.

67 With the exception of exercise 

training, due to the nature of the interventions the potential for serious adverse events is unlikely; 

however, the evidence is insufficient to draw any conclusions.

KEY QUESTION 5: Do the benefits or harms of screening differ by

subpopulation?

We identified 1 study that examined differences in the benefits or harms of depression screening 

in patients with ESRD. A small (N = 43) multisite diagnostic accuracy study conducted in UK 

outpatient hemodialysis units compared depression screening (BDI, CDI) completed on and off 

dialysis.53 Findings indicated that there was generally a high level of agreement, particularly 

among depressed patients. However, non-depressed patients had higher mean overall BDI-II 

(9.6[6.2] versus 7.3[5.7], P = 0.007) and somatic symptom item scores (4.4[2.5] versus 3.3[2.1], 

P = 0.01) on assessments completed while undergoing dialysis. 

KEY QUESTION 6: Do the benefits or harms of treatment differ by

subpopulation?

Three trials examined differences in the benefits or harms of interventions for the treatment 

depression in patients with ESRD by subpopulation. Interventions examined were omega-3 fatty 

acids,66 high-dose vitamin D3,

65 and CBT.69

Patient Characteristics

Two trials explored differences in effect by patient clinical and demographic characteristics. A 

large, multisite fair-quality trial (N = 746) of high-dose vitamin D3 found no differences in effect 

by age or gender, body mass index (BMI), or plasma albumin level. However, findings did 

indicate that among participants with vascular depression, and not major depressive disorder,

those who received Vitamin K reported a significantly greater reduction in depressive symptoms 

at one year than those receiving placebo.65 The second was a small (N = 54), poor-quality trial 

examining the use of omega-3 fatty acids. It found no significant difference in benefits or harms 

by age, gender, baseline depression severity, nor length of time on hemodialysis (see Table 8 and 

9, and Appendix E for more detail).

66

Timing and Type of Follow-up

A small, fair-quality trial (N = 65)69 comparing CBT to waitlist control examined differences in 

depressive symptoms, quality of life, and fluid compliance based on the timing of the 

intervention (first or after 90-day waitlist). In both phases, participants who received CBT 

experienced significantly greater benefits across outcomes. Findings suggest a sequence effect 

for depressive symptom reduction (greater benefit for first group versus waitlist), but none for 

quality of life or fluid compliance (see Table 7 and 8, and Appendix E for more detail).69
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DISCUSSION

We identified 16 studies evaluating the diagnostic accuracy of a variety of depression screening 

tools, and 20 RCTs examining the effectiveness of pharmacological and non-pharmacological

interventions for adults with ESRD and depression. Overall, samples included in studies 

evaluating screening tools bear little resemblance to Veterans seeking care in VHA settings. In 

addition, except for the BDI-II, the evidence base is quite limited due to the small number of 

studies examining each tool and small samples. Similarly, for intervention studies, we identified 

limited research for each intervention, sample sizes were small, and nearly all studies were 

hampered by methodological flaws.

The BDI-II was by far the best-studied screening tool. However, there was heterogeneity in the 

way depression was operationalized. Half of the studies evaluated the performance 

characteristics associated with thresholds intended to screen for MDD, while the other half 

defined depression more loosely, with some including subclinical depressive symptoms. Among 

the studies evaluating the BDI-II as a tool to identify MDD, the threshold that best optimized the 

balance between sensitivity and specificity for patients with ESRD was ≥16. Interestingly, this 

finding was reported in the single study that screened for MDD specifically and included a VHA 

population. Of note, the PHQ-9 tool is commonly used in VHA primary care settings, but we

identified only a single, 15-year-old study evaluating it in this patient population.44

Table 11 uses data from the 2 US39,44 and 2 UK studies50,53 that screened specifically for MDD to 

compare positive and negative predictive values across reported MDD prevalence rates for a) the 

general US population (7.1%)3; b) Veterans receiving care in VHA patient-centered medical 

homes (Patient Aligned Care Teams [PACT]; 13.5%)

9

; c) patients with ESRD, diagnosed using a 

gold standard clinical interview (22.8%)4; d) Veterans with ESRD (method of diagnosis NR; 

33%)10; and e) patients with ESRD, diagnosed using a screening tool (39.3%).4 Although these 

rates are representative of US populations, we included the 2 UK studies because the population 

and health system is similar to the VHA. Studies evaluate both the BDI-II and the PHQ-9 and

highlight the impact of the population specific prevalence rate on positive and negative 

predictive values for a specific threshold. Across studies, the negative predictive values, or 

accuracy of eliminating depression as a diagnosis are generally high, and false negative findings 

are unlikely. However, the positive predictive values, or accuracy of correctly diagnosing 

depression, range from 0.26 to 0.88, and depending on the population, potential of a false 

positive may be high. Providers should keep this in mind if using the results of depression 

screening tools to guide treatment decisions.

Across the 4 BDI-II studies, a cutoff of ≥16 provides the best balance between sensitivity and 

specificity. In fact, we found that in some studies, the BDI-II performed reasonably well when 

compared to a gold standard clinical interview. The caveat however, is that there was 

heterogeneity across studies in the way the tools were administered, and very few studies 

contributed data for the same thresholds. Most of the diagnostic accuracy studies were conducted 

outside of the US, and/or in health systems that differ from the VHA. Studies of non-Veterans

with ESRD may also be less applicable due to both demographic (eg, gender, socioeconomic and 

housing status) and clinical differences (eg, multiple comorbidities, substance use, mental 

health). 
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Table 11. Positive and negative predictive values associated with depression rates in 4 US

populations

Author, Year

N, % MDD 

(Ref), % MDD 

Tool, Cutoff

Sensitivity 

(%)

Specificity 

(%)

Prevalence 

Assumption 

(%)

Positive 

Predictive 

Value

Negative 

Predictive Value

Beck Depression Inventory-II (BDI-II)

Balogun, 

201139

N = 96

30.6%, 37.1%

BDI ≥10

68 77

7.1a 0.88 0.50

13.5b 0.32 0.94

22.8c 0.47 0.89

33.0d 0.59 0.83

39.3e 0.66 0.79

Watnick, 

200544

N = 62

19.4%, NR

BDI ≥16

91 86

7.1a 0.33 0.99

13.5b 0.50 0.98

22.8c 0.66 0.97

33.0d 0.76 0.95

39.3e 0.81 0.94

Chilcot, 200853

N = 40

22.5%; 30-

32.5%

BDI ≥16

88.9 87.1

7.1a 0.35 0.99

13.5b 0.52 0.98

22.8c 0.67 0.96

33.0d 0.77 0.94

39.3e 0.82 0.92

Grant, 2008

N = 57

12.3%; 31.6%

BD I≥15 

100 78

7.1a 0.26 1.0

13.5b 0.42 1.0

22.8c 0.57 1.0

33.0d 0.69 1.0

39.3e 0.74 1.0

Patient Health Questionnaire 9 (PHQ-9)

Watnick, 

200544

N = 62

19.4%, NR

PHQ-9≥10 

92 92

7.1a 0.47 0.99

13.5b 0.64 0.99

22.8c 0.77 0.97

33.0d 0.85 0.96

39.3e 0.88 0.95 a General US population, b Veterans receiving care in VHA patient-centered medical homes, c Patients with ESRD, 

diagnosed using a gold standard clinical interview, d Veterans with ESRD (diagnosis method NR), e Patients with 

ESRD, diagnosed using a screening tool. 

Abbreviations: BDI-II = Beck Depression Inventory-II; MDD = Major Depressive Disorder

Studies evaluating a (typically short) screening tool against an established validated tool 

performed well overall. Since the QIP requires a follow-up assessment after an initial positive 

screen, these short tools may be good options for this purpose. In particular, the BDI-FS 

performed well when compared to the BDI-II. 
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We identified no studies examining the impact of screening on intermediate or health outcomes. 

Only 1 study examined subgroup differences in screening, and it found that non-depressed 

participants reported significantly more somatic symptoms when depression screening was 

administered during dialysis sessions versus off dialysis. Not only were scores on somatic items 

significantly higher, but BDI-II scores were significantly higher as well. This has implications 

for dialysis units working to streamline processes, as it illustrates the potential for over-diagnosis 

and over-treatment. 

SSRIs, compared either to placebo or an active comparator, were the best-studied 

pharmacological intervention. Findings from placebo-controlled trials were mixed, and the 

evidence is insufficient due to lack of consistent findings, small samples, and other methodologic 

flaws. We found low-strength evidence that despite improvement in both treatment groups, there 

is no difference between sertraline and CBT. We found moderate-strength evidence that high 

dose vitamin D3 is ineffective for reducing depressive symptoms. Vitamin D3 is an interesting 

intervention for patients with ESRD, due to the risk of hyperphosphatemia in this population, 

which can be exacerbated by vitamin D. Five patients withdrew from the study due to treatmentrelated AEs. Though not attributed to hyperphosphatemia, the reported AEs (ie, joint pain, 

diarrhea, nausea and vomiting) may be related.

Across non-pharmacological interventions, we found low-strength evidence that CBT is more 

effective than psychotherapy or placebo for reducing depression severity and increasing quality 

of life. We also found low-strength evidence that acupressure is more effective for reducing 

depression severity than sham or usual care. Findings for all other non-pharmacological

interventions were insufficient to draw conclusions.
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Table 12. Strength of evidence of intervention effectiveness

Note. Colors represent the Strength of Evidence (SOE). Gray = Insufficient, yellow = low SOE, blue = moderate

SOE. 

Abbreviations: CBT = cognitive behavioral therapy, MBSR = mindfulness-based stress reduction, SSRI = selective 

serotonin reuptake inhibitor, TAU = treatment as usual.
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Very few intervention studies reported harms; however, most interventions presented minimal 

risk. Harms related to SSRIs were not uniformly reported. That said, the type and rate of harms 

reported and or evaluated in multiple studies suggest little to no increase in risk compared to 

otherwise healthy individuals using SSRIs.

Differences by subpopulation were reported in very few studies, and no reported differences 

were insufficient to form conclusions.

LIMITATIONS

There are several important limitations to this evidence base, in addition to small samples sizes 

and a limited number of studies examining specific tool thresholds and specific interventions. 

Across studies of both screening and treatment, a good number of studies were conducted 

outside of the United States, many of which examined participants and health systems that differ 

from general US and Veteran populations. In addition, the lack of methodological detail reported 

in many of the studies resulted in poor quality ratings, and uncertainty about study processes. For 

screening studies, the definition of depression varied widely, which hampered our ability to 

synthesize the body of research for each tool. Future studies should use standardized language 

(eg, DSM-580).

For intervention studies, there was significant heterogeneity in outcome measures used to assess 

depressive symptoms, and it is possible that the small sample sizes in many of the studies 

resulted in a lack of power to detect differences.

This is the only systematic review to date that examines the breadth of both screening and 

treatment of depression in adults with ESRD. This review confirms and adds to a 2016 Cochrane 

review of antidepressants in adults with ESRD that included meta-analyses of harms reported in 

trials included in our report.81 Although we also included more recent trials, outcomes were not 

reported in a way that allowed for a quantitative synthesis of harms. Newer trials included in our 

review, particularly the ASCEND (A Trial of Sertraline vs. Cognitive Behavioral Therapy for 

End-stage Renal Disease Patients with Depression) trial,63 add to both the pharmacological and 

non-pharmacological evidence.

RESEARCH GAPS/FUTURE RESEARCH

There are many areas ripe for further research in this field. As described above, diagnostic 

accuracy studies of depression tools conducted in US and Veteran ESRD populations are needed. 

In addition, the PHQ-9 is a commonly used tool in VHA and community settings. Additional 

research evaluating its performance characteristics is warranted. There are a handful of studies 

supporting the use of the BDI-II as a screening tool for MDD in this population. Larger studies 

with representative samples evaluating a range of thresholds would help to guide decisionmaking and implementation. Relatedly, there were several high-performing tools that used the 

BDI-II as a reference standard. Short, population-targeted tools (eg, BDI-FS, GDS-15) may be 

appropriate as an initial screen for depression in dialysis settings. However, more research is 

needed to validate existing findings. Finally, the DI-MHD was the only screening tool we 

identified developed specifically for this population. It performed well as compared to the BDI in 

a large sample in China; however, to date it has not been compared to a gold standard clinical 
ESRD and Depression Evidence Synthesis Program

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interview. Additional research validating the DI-MHD has the potential to impact screening 

practices in this population.

We identified no studies examining the impact of screening on outcomes, and only 1 study that 

examined subgroup differences. This study compared differences in overall and somatic BDI-II 

scores when completed on versus off dialysis and touches on only 1 of many important 

implementation issues (eg, timing, location, administration). Also important but missing is 

evidence of potential demographic and clinical differences. Research in these areas will help 

decisionmakers to implement screening processes that are not only evidence-based, but also the 

best fit for their patient population.

Future research is also needed to better evaluate both pharmacological and non-pharmacological

interventions for this population. 

IMPLICATIONS FOR THE VHA

Our findings have several implications for the VHA. They will be used to help guide the 

selection and implementation of screening for Veterans with ESRD, and the interventions for 

those with comorbid depressive disorders. They will also help to guide future Health Services 

Research and Development (HSR&D) priorities. Currently in VHA settings, Veterans with 

ESRD are screened for depression using a variety of tools, including the PHQ-9. Our findings 

highlight the moderate positive predictive values in this population. Clinicians should be 

prepared to validate positive screens prior to making treatment decisions that may be 

burdensome or introduce the possibility of harm.

CONCLUSION

There is limited research evaluating the diagnostic accuracy of most screening tools for 

depression in patients with ESRD, and the existing studies may not be generalizable to patients 

in the US, or Veterans receiving care in VHA settings. Screening and intervention studies suffer 

from limitations related to methodological quality or reporting. In adults with ESRD, the BDI-II 

with a cutoff of ≥16 provides a good balance of sensitivity and specificity. More research is 

needed to support the use of other tools. We found low-strength evidence that sertraline and CBT 

provide benefit for depressive symptoms. There is low-strength evidence that CBT is more 

effective than psychotherapy or placebo for depressive symptoms and quality of life, lowstrength evidence that acupressure is more effective for reducing depression than sham or usual 

care, and moderate-strength evidence that high-dose vitamin D3 is ineffective. Although our 

ability to form conclusions about the effectiveness of interventions for depression in patients 

with ESRD is limited, it is important to note that across studies within group improvements were 

common, despite insignificant differences between groups, suggesting that treatment generally 

may be better than no treatment in this population. More research is needed.
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REFERENCES

1. United States Renal Data System. Chapter 1: Incidence, Prevalence, Patient 

Characteristics, and Treatment Modalities. United States Renal Data System;2018.

2. Crowley ST, Murphy K. Delivering a "New Deal" of Kidney Health Opportunities to 

Improve Outcomes Within the Veterans Health Administration. Am J Kidney Dis. 

2018;72(3):444-450.

3. National Institute of Mental Health. Major Depression. Mental Health Information: 

Statistics 2017; https://www.nimh.nih.gov/health/statistics/major-depression.shtml. 

Accessed Oct 31, 2019.

4. Palmer S, Vecchio M, Craig JC, et al. Prevalence of depression in chronic kidney disease: 

systematic review and meta-analysis of observational studies. Kidney Int. 

2013;84(1):179-191.

5. Xing L, Chen R, Diao Y, Qian J, You C, Jiang X. Do psychological interventions reduce 

depression in hemodialysis patients?: A meta-analysis of randomized controlled trials 

following PRISMA. Medicine. 2016;95(34):e4675.

6. Farrokhi F, Abedi N, Beyene J, Kurdyak P, Jassal SV. Association between depression 

and mortality in patients receiving long-term dialysis: a systematic review and metaanalysis. Am J Kidney Dis. 2014;63(4):623-635.

7. Weisbord SD, Mor MK, Sevick MA, et al. Associations of depressive symptoms and pain 

with dialysis adherence, health resource utilization, and mortality in patients receiving 

chronic hemodialysis. Clinical Journal of The American Society of Nephrology: CJASN. 

2014;9(9):1594-1602.

8. Kurella M, Kimmel PL, Young BS, Chertow GM. Suicide in the United States end-stage 

renal disease program. J Am Soc Nephrol. 2005;16(3):774-781.

9. Trivedi RB, Post EP, Sun H, et al. Prevalence, Comorbidity, and Prognosis of Mental 

Health Among US Veterans. Am J Public Health. 2015;105(12):2564-2569.

10. United States Renal Data System. 2017 USRDS Annual Data Report. 2017.

11. Centers for Medicare & Medicaid Services. ESRD Quality Incentive Program. 2018; 

https://www.cms.gov/medicare/quality-initiatives-patient-assessmentinstruments/esrdqip/. Accessed April 5, 2018.

12. Shirazian S, Grant CD, Aina O, Mattana J, Khorassani F, Ricardo AC. Depression in 

Chronic Kidney Disease and End-Stage Renal Disease: Similarities and Differences in 

Diagnosis, Epidemiology, and Management. KI Reports. 2017;2(1):94-107.

13. Sullivan JE, Choi NG, Vazquez CE, Neaves MA. Psychosocial Depression Interventions 

for Dialysis Patients, With Attention to Latinos: A Scoping Review. Research on Social 

Work Practice. 2019;29(8):910-923.

14. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer 

Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 

2016;75:40-46.

15. Wallace BC, Small K, Brodley CE, Lau J, Trikalinos TA. Deploying an interactive 

machine learning system in an evidence-based practice center: abstrackr. Proceedings of 

the 2nd ACM SIGHIT International Health Informatics Symposium (IHI). 2012:819-824.

16. Department of Veterans Affairs, Department of Defense. VA/DoD CLINICAL 

PRACTICE GUIDELINE FOR THE MANAGEMENT OF MAJOR DEPRESSIVE 

DISORDER. April 2016 2016.
ESRD and Depression Evidence Synthesis Program

76

17. CMS Center for Clinical Standards & Quality. Summary of Representative Clinical 

Depression Screening Tools. November 30, 2015 2015.

18. Furukawa TA, Reijnders M, Kishimoto S, et al. Translating the BDI and BDI-II into the 

HAMD and vice versa with equipercentile linking. Epidemiol Psychiatr Sci. 2019:1-13.

19. Stafford L, Berk M, Jackson HJ. Validity of the Hospital Anxiety and Depression Scale 

and Patient Health Questionnaire-9 to screen for depression in patients with coronary 

artery disease. Gen Hosp Psychiatry. 2007;29(5):417-424.

20. Applied Health Sciences (Mental Health). Assessing the validity of the PHQ-9, HADS, 

BDI-II and QIDS-SR in measuring severity of depression in a UK sample of primary care 

patients with a diagnosis of depression. University of Aberdeen2011.

21. Treadwell JR, Singh S, Talati R, McPheeters ML, Reston JT. A framework for best 

evidence approaches can improve the transparency of systematic reviews. J Clin 

Epidemiol. 2012;65(11):1159-1162.

22. O'Connor E, Rossom RC, Henninger M, et al. Screening for Depression in Adults: An 

Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. In: 

U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence 

Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016.

23. U.S. Preventive Services Task Force. Appendix VII. Criteria for Assessing External 

Validity (Generalizability) of Individual Studies. 2017; 

https://www.uspreventiveservicestaskforce.org/Page/Name/appendix-vii-criteria-forassessing-external-validity-generalizability-of-individual-studies.

24. U.S. Preventive Services Task Force. Appendix VI. Criteria for Assessing Internal 

Validity of Individual Studies. 2017; 

https://www.uspreventiveservicestaskforce.org/Page/Name/appendix-vi-criteria-forassessing-internal-validity-of-individual-studies

25. Whiting PF, Rutjes AWS, Westwood ME, et al. QUADAS-2: A Revised Tool for the 

Quality Assessment of Diagnostic Accuracy Studies. Ann Intern Med. 2011;155(8):529-

536.

26. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing 

the quality of nonrandomised studies in meta-analyses.

http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

27. Beck AT, Steer RA, Brown GK. BDI-II: Beck Depression Inventory Manual. Second ed. 

San Antonio: Psychological Corporation; 1996.

28. Lowry R. Predictive Values and Likelihood Ratios. http://vassarstats.net/clin2.html. 

Accessed Nov 1, 2019.

29. Berkman ND, Lohr KN, Ansari MT, et al. Grading the strength of a body of evidence 

when assessing health care interventions: an EPC update. J Clin Epidemiol. 

2015;68(11):1312-1324.

30. Atkins D, Chang SM, Gartlehner G, et al. Assessing applicability when comparing 

medical interventions: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 

2011;64(11):1198-1207.

31. Kimmel PL, Weihs K, Peterson RA. Survival in hemodialysis patients: the role of 

depression. J Am Soc Nephrol. 1993;4(1):12-27.

32. The Center for Innovative Public Health Research. CESD-R: The Center for 

Epidemiologic Studies Depression Scale Revised. https://cesd-r.com/about-cesdr/. 

Accessed Nov 1, 2019.
ESRD and Depression Evidence Synthesis Program

77

33. Hedayati SS, Bosworth HB, Kuchibhatla M, Kimmel PL, Szczech LA. The predictive 

value of self-report scales compared with physician diagnosis of depression in 

hemodialysis patients. Kidney Int. 2006;69(9):1662-1668.

34. Snaith RP, Zigmond AS. The hospital anxiety and depression scale. Br Med J (Clin Res 

Ed). 1986;292(6516):344.

35. Loosman WL, Siegert CE, Korzec A, Honig A. Validity of the Hospital Anxiety and 

Depression Scale and the Beck Depression Inventory for use in end-stage renal disease 

patients. Br J Clin Psychol. 2010;49(Pt 4):507-516.

36. Preljevic VT, Osthus TB, Sandvik L, et al. Screening for anxiety and depression in 

dialysis patients: comparison of the Hospital Anxiety and Depression Scale and the Beck 

Depression Inventory. J Psychosom Res. 2012;73(2):139-144.

37. Sheikh JI, Yesavage JA. Geriatric Depression Scale (GDS): Recent evidence and 

development of a shorter version. Clinical Gerontology. 1986;5:165-173.

38. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric 

depression screening scale: A preliminary report. J Psychiatr Res. 1982;17(1):37-49.

39. Balogun RA, Turgut F, Balogun SA, Holroyd S, Abdel-Rahman EM. Screening for 

depression in elderly hemodialysis patients. Nephron. 2011;118(2):c72-77.

40. Giordano M, Tirelli P, Ciarambino T, et al. Screening of depressive symptoms in youngold hemodialysis patients: relationship between Beck Depression Inventory and 15-item 

Geriatric Depression Scale. Nephron. 2007;106(4):c187-192.

41. Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin 

Psychol. 1967;6(4):278-296.

42. Gencoz F, Gencoz T, Soykan A. Psychometric properties of the Hamilton Depression 

Rating Scale and other physician-rated psychiatric scales for the assessment of depression 

in ESRD patients undergoing hemodialysis in Turkey. Psychology Health & Medicine. 

2007;12(4):450-459.

43. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity 

measure. J Gen Intern Med. 2001;16(9):606-613.

44. Watnick S, Wang PL, Demadura T, Ganzini L. Validation of 2 depression screening tools 

in dialysis patients. Am J Kidney Dis. 2005;46(5):919-924.

45. Wang YY, Zhang WW, Feng L, et al. Development and Preliminary Validation of a 

Depression Assessment Tool for Maintenance Hemodialysis Patients. Therapeutic 

Apheresis & Dialysis: Official Peer-Reviewed Journal of the International Society for 

Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 

2019;23(1):49-58.

46. Neitzer A, Sun S, Doss S, Moran J, Schiller B. Beck Depression Inventory-Fast Screen 

(BDI-FS): an efficient tool for depression screening in patients with end-stage renal 

disease. Hemodialysis International. 2012;16(2):207-213.

47. Troidle L, Wuerth D, Finkelstein S, Kliger A, Finkelstein F. The BDI and the SF36: 

which tool to use to screen for depression? Adv Perit Dial. 2003;19:159-162.

48. Bautovich A, Katz I, Loo CK, Harvey SB. Beck Depression Inventory as a screening tool 

for depression in chronic haemodialysis patients. Australasian Psychiatry. 

2018;26(3):281-284.

49. Collister D, Rodrigues JC, Mazzetti A, et al. Single Questions for the Screening of 

Anxiety and Depression in Hemodialysis. Canadian Journal of Kidney Health & 

Disease. 2019;6:2054358118825441.
ESRD and Depression Evidence Synthesis Program

78

50. Grant D, Almond MK, Newnham A, Roberts P, Hutchings A. The Beck Depression 

Inventory requires modification in scoring before use in a haemodialysis population in 

the UK. Nephron. 2008;110(1):c33-38.

51. van den Beukel TO, Siegert CE, van Dijk S, Ter Wee PM, Dekker FW, Honig A. 

Comparison of the SF-36 Five-item Mental Health Inventory and Beck Depression 

Inventory for the screening of depressive symptoms in chronic dialysis patients. 

Nephrology Dialysis Transplantation. 2012;27(12):4453-4457.

52. Alsuwaida A, Alwahhabi F. The diagnostic utility of Self-Reporting Questionnaire (SRQ) 

as a screening tool for major depression in hemodialysis patients. Saudi J Kidney Dis 

Transpl. 2006;17(4):503-510.

53. Chilcot J, Wellsted D, Farrington K. Screening for depression while patients dialyse: an 

evaluation. Nephrology Dialysis Transplantation. 2008;23(8):2653-2659.

54. First M. User's guide for the Structured clinical interview for DSM-IV axis I disorders 

SCID-I : Clinician version. Washington, DC: American Psychiatric Press; 1997.

55. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric 

Interview (M.I.N.I.): the development and validation of a structured diagnostic 

psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-

33;quiz 34-57.

56. Hedayati. Accuracy of depression evaluation in hemodialysis patients. Nature Clinical 

Practice Nephrology. 2006;2(8):409-410.

57. Sacks CR, Peterson RA, Kimmel PL. Perception of Illness and Depression in Chronic 

Renal Disease. Am J Kidney Dis. 1990;15(1):31-39.

58. World Health Organization. A User's Guide to the Self Reporting Questionnaire (SRQ). 

Geneva: Division of Mental Health World Health Organization,;1994.

59. Beck AT, Steer RA, Brown GK. BDI - FastScreen for Medical Patients.

https://www.pearsonassessments.com/store/usassessments/en/Store/ProfessionalAssessments/Personality-%26-Biopsychosocial/Brief/BDI---FastScreen-for-MedicalPatients/p/100000173.html?tab=product-details.

60. Blumenfield M, Levy NB, Spinowitz B, et al. Fluoxetine in depressed patients on 

dialysis. Int J Psychiatry Med. 1997;27(1):71-80.

61. Friedli K, Guirguis A, Almond M, et al. Sertraline Versus Placebo in Patients with Major 

Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility 

Trial. Clinical Journal of The American Society of Nephrology: CJASN. 2017;12(2):280-

286.

62. Taraz M, Khatami MR, Dashti-Khavidaki S, et al. Sertraline decreases serum level of 

interleukin-6 (IL-6) in hemodialysis patients with depression: results of a randomized 

double-blind, placebo-controlled clinical trial. Int Immunopharmacol. 2013;17(3):917-

923.

63. Mehrotra R, Cukor D, Unruh M, et al. Comparative Efficacy of Therapies for Treatment 

of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized 

Clinical Trial. Ann Intern Med. 2019;26:26.

64. Hosseini SH, Espahbodi F, Mirzadeh Goudarzi SM. Citalopram versus psychological 

training for depression and anxiety symptoms in hemodialysis patients. Iran J Kidney 

Dis. 2012;6(6):446-451.

65. Wang Y, Liu Y, Lian Y, Li N, Liu H, Li G. Efficacy of High-Dose Supplementation With 

Oral Vitamin D3 on Depressive Symptoms in Dialysis Patients With Vitamin D3 
ESRD and Depression Evidence Synthesis Program

79

Insufficiency: A Prospective, Randomized, Double-Blind Study. J Clin 

Psychopharmacol. 2016;36(3):229-235.

66. Gharekhani A, Khatami MR, Dashti-Khavidaki S, et al. The effect of omega-3 fatty acids 

on depressive symptoms and inflammatory markers in maintenance hemodialysis 

patients: a randomized, placebo-controlled clinical trial. Eur J Clin Pharmacol. 

2014;70(6):655-665.

67. Duarte PS, Miyazaki MC, Blay SL, Sesso R. Cognitive-behavioral group therapy is an 

effective treatment for major depression in hemodialysis patients. Kidney Int. 

2009;76(4):414-421.

68. Al Saraireh FA, Aloush SM, Al Azzam M, Al Bashtawy M. The Effectiveness of 

Cognitive Behavioral Therapy versus Psychoeducation in the Management of Depression 

among Patients Undergoing Haemodialysis. Issues Ment Health Nurs. 2018;39(6):514-

518.

69. Cukor D, Ver Halen N, Asher DR, et al. Psychosocial intervention improves depression, 

quality of life, and fluid adherence in hemodialysis. J Am Soc Nephrol. 2014;25(1):196-

206.

70. Lerma A, Perez-Grovas H, Bermudez L, Peralta-Pedrero ML, Robles-Garcia R, Lerma C. 

Brief cognitive behavioural intervention for depression and anxiety symptoms improves 

quality of life in chronic haemodialysis patients. Psychology & Psychotherapy: Theory, 

Research & Practice. 2017;90(1):105-123.

71. Kalani L, Aghababaeian H, Majidipour N, et al. The effects of acupressure on severity of 

depression in hemodialysis patients: a randomized controlled trial. Journal of Advanced 

Pharmacy Education & Research. 2019;9(S2):67-72.

72. Tsay SL, Cho YC, Chen ML. Acupressure and Transcutaneous Electrical Acupoint 

Stimulation in improving fatigue, sleep quality and depression in hemodialysis patients. 

Am J Chin Med. 2004;32(3):407-416.

73. Heshmatifar N SHMASNMRRMH. The effect of benson relaxation technique on 

depression in patients undergoing hemodialysis. Journal of babol university of medical 

sciences. 2015;17(8):34.

74. Kouidi E, Karagiannis V, Grekas D, et al. Depression, heart rate variability, and exercise 

training in dialysis patients. Eur J Cardiovasc Prev Rehabil. 2010;17(2):160-167.

75. Beizaee Y, Rejeh N, Heravi-Karimooi M, Tadrisi SD, Griffiths P, Vaismoradi M. The 

effect of guided imagery on anxiety, depression and vital signs in patients on 

hemodialysis. Complement Ther Clin Pract. 2018;33:184-190.

76. Rahimipour M, Shahgholian N, Yazdani M. Effect of hope therapy on depression, 

anxiety, and stress among the patients undergoing hemodialysis. Iran J Nurs Midwifery 

Res. 2015;20(6):694-699.

77. Widyaningrum, Siswanto A, Djarwoto B. Effects of Latihan Pasrah Diri in Quality Of 

Life in Chronic Kidney Disease-Dialysis Patients with Depression Symptoms. Acta 

Interna - The Journal of Internal Medicine. 2013;3(2):16-22.

78. Thomas Z, Novak M, Platas SGT, et al. Brief Mindfulness Meditation for Depression and 

Anxiety Symptoms in Patients Undergoing Hemodialysis: A Pilot Feasibility Study. 

Clinical Journal of The American Society of Nephrology: CJASN. 2017;12(12):2008-

2015.
ESRD and Depression Evidence Synthesis Program

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79. Babamohamadi H, Sotodehasl N, Koenig HG, Al Zaben F, Jahani C, Ghorbani R. The 

Effect of Holy Qur'an Recitation on Depressive Symptoms in Hemodialysis Patients: A 

Randomized Clinical Trial. Journal of Religion & Health. 2017;56(1):345-354.

80. American Psychiatric Association. Diagnostic and Statistical Manual of Mental 

Disorders. Fifth ed. Arlington, VA: American Psychiatric Association; 2013.

81. Palmer SC, Natale P, Ruospo M, et al. Antidepressants for treating depression in adults 

with end-stage kidney disease treated with dialysis. Cochrane Database of Systematic 

Reviews. 2016(5):CD004541.
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APPENDIX A. SEARCH STRATEGIES

Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations 

and Daily 1946 to May 16, 2019 

Date searched: May 17, 2019 

# Searches Results

1 Kidney Failure, Chronic/ 90023

2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or 

maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab,kf.

173570

3 Renal Dialysis/ or Hemofiltration/ or Hemodiafiltration/ or Hemodialysis, Home/ or Peritoneal 

Dialysis/ or Peritoneal Dialysis, Continuous Ambulatory/

112477

4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or 

haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or 

hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab,kf.

148887

5 or/1-4 306563

6 Depression/ or Depressive Disorder/ or Depressive Disorder, Major/ or Depressive Disorder, 

Treatment-Resistant/

196624

7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab,kf. 461502

8 or/6-7 498556

9 and/5,8 4467

10 Brief Psychiatric Rating Scale/ or Diagnostic Self Evaluation/ or "Diagnostic Techniques and 

Procedures"/ or Mental Status Schedule/ or Neuropsychological Tests/ or Patient Health 

Questionnaire/ or Psychiatric Status Rating Scales/ or exp Psychological Tests/ or exp "Surveys 

and Questionnaires"/

1191872

11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or 

inventory or inventories or scale or scales or schedule or schedules or screen or screened or 

screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or 

"Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or 

"Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health 

Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple 

Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or 

PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD 

or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or 

2055783
ESRD and Depression Evidence Synthesis Program

82

QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or 

"Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form 

Health Survey 36" or SF36).ti,ab,kf.

12 exp Behavior Therapy/ or exp Cognitive Behavioral Therapy/ or exp Mental Health Services/ or 

exp Psychotherapy/ or Psychosocial Support Systems/ or Social Support/ or Motivational 

Interviewing/ or Patient Participation/

348454

13 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or nondrug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or 

psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab,kf.

7986725

14 Antidepressive Agents/ or Antidepressive Agents, Second-generation/ or Serotonin Uptake 

Inhibitors/ or "Serotonin and Noradrenaline Reuptake Inhibitors"/ or Adrenergic Uptake Inhibitors/ 

or 5-hydroxytryptophan/ or Amisulpride/ or Bupropion/ or Citalopram/ or Fluoxetine/ or 

Fluvoxamine/ or Maprotiline/ or Mianserin/ or Paroxetine/ or Quipazine/ or Ritanserin/ or Sulpiride/ 

or Trazodone/ or Tryptophan/ or Venlafaxine Hydrochloride/ or Viloxazine/

110464

15 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram 

or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or 

Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or 

Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or 

SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and 

Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or 

"norepinephrine reuptake inhibitors").ti,ab,kf.

143600

16 Antidepressive Agents, Tricyclic/ or Amitriptyline/ or Amoxapine/ or Clomipramine/ or 

Desipramine/ or Dothiepin/ or Doxepin/ or Imipramine/ or Iprindole/ or Lofepramine/ or 

Nortriptyline/ or Opipramol/ or Protriptyline/ or Trimipramine/

30787

17 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or 

Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or 

Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab,kf,nm.

46116

18 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab,kf. 19983

19 Exercise Therapy/ or Resistance Training/ 43818

20 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 

(program* or therap* or train*)) or cross-training).ti,ab,kf.

59756

21 Music Therapy/ 3247
ESRD and Depression Evidence Synthesis Program

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22 music therapy.ti,ab,kf. 2112

23 or/10-22 9783531

24 and/9,23 3317

25 limit 24 to english language 2949

PsycINFO 1806 to May Week 1 2019 

Date searched: May 16, 2019 

Searches Results

1 Kidney Diseases/ 2042

2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or 

maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab.

2810

3 Dialysis/ or Hemodialysis/ 1775

4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or 

haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or 

hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab.

2862

5 or/1-4 5141

6 "Depression (Emotion)"/ or Major Depression/ or Reactive Depression/ or Recurrent Depression/ 

or Treatment Resistant Depression/

140804

7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 317296

8 or/6-7 323277

9 and/5,8 865

10 exp Measurement/ or exp Attitude Measures/ or exp "Checklist (Testing)"/ or exp Inventories/ or 

exp Psychological Assessment/ or exp Questionnaires/ or exp Rating Scales/ or exp Screening/ or 

exp Screening Tests/ or exp Standardized Tests/ or exp "Stress and Coping Measures"/ or exp 

Testing/

338213

11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or 

inventory or inventories or scale or scales or schedule or schedules or screen or screened or 

screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or 

"Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or 

"Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health 

Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple 

742562
ESRD and Depression Evidence Synthesis Program

84

Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or 

PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD 

or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or 

QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or 

"Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form 

Health Survey 36" or SF36).ti,ab.

12 ("Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating 

Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease 

Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOSSF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective 

Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or PHQ9 or PHQ-9 or 

PHQ-ADS or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or 

BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or 

QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or 

"Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form 

Health Survey 36" or SF36).tm.

121323

13 exp Treatment/ 713235

14 exp Behavior Modification/ or exp Behavior Therapy/ or Biofeedback Training/ or Contingency 

Management/ or Self-management/ or Anxiety Management/ or Cognitive Therapy/ or Readiness 

to Change/ or Relaxation Therapy/ or Self-help Techniques/ or Self-monitoring/ or Stress 

Management/

68176

15 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or nondrug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or 

psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab.

2004054

16 Antidepressant Drugs/ or Serotonin Norepinephrine Reuptake Inhibitors/ or Serotonin Reuptake 

Inhibitors/ or Tricyclic Antidepressant Drugs/ or Bupropion/ or Citalopram/ or Fluoxetine/ or 

Fluvoxamine/ or "Hydroxytryptophan (5-)"/ or MAPROTILINE/ or Mianserin/ or Paroxetine/ or 

RITANSERIN/ or Sulpiride/ or Trazodone/ or Tryptophan/ or Venlafaxine/

32404

17 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram 

or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or 

Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or 

Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or 

SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and 

55680
ESRD and Depression Evidence Synthesis Program

85

Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or 

"norepinephrine reuptake inhibitors").ti,ab.

18 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or 

Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or 

Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab.

12077

19 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog* or coping or psychosocial* or 

psycho-social* or "social support" or "social work*" or stress).ti,ab.

373419

20 exp Exercise/ 24633

21 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 

(program* or therap* or train*)) or cross-training).ti,ab.

7962

22 Music Therapy/ 4568

23 music therapy.ti,ab. 3920

24 or/10-23 2709627

25 and/9,24 813

26 limit 25 to english language 708

Embase.com 

Date search: May 17, 2019 

# Search Result

#26 #25 AND [embase]/lim NOT ([embase]/lim AND [medline]/lim) 2,398

#25 #9 AND #23 AND [english]/lim 5,827

#24 #9 AND #23 6,404

#23 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 

OR #19 OR #20 OR #21 OR #22

11,480,368

#22 'music therapy':ti,ab,kw 3,312

#21 'music therapy'/de 6,432

#20 (((aerobic OR resistance) NEAR/2 

(exercis* OR program* OR therap* OR train*)):ti,ab,kw) OR 

((exercise NEAR/2 (program* OR therap* OR train*)):ti,ab,kw) 

OR 'cross training':ti,ab,kw

85,478

#19 'kinesiotherapy'/de OR 'resistance training'/de 46,613

#18 nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmacolog*:ti,ab,kw 

OR 'non pharmacolog*':ti,ab,kw

28,848

#17 amitriptyline:ti,ab,kw OR amoxapine:ti,ab,kw 

OR clomipramine:ti,ab,kw OR desipramine:ti,ab,kw 

49,716
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OR dothiepin:ti,ab,kw OR doxepin:ti,ab,kw OR imipramine:ti,ab,kw 

OR iprindole:ti,ab,kw OR lofepramine:ti,ab,kw 

OR nortriptyline:ti,ab,kw OR opipramol:ti,ab,kw 

OR protriptyline:ti,ab,kw OR trimipramine:ti,ab,kw 

OR gabapentin:ti,ab,kw OR sildenafil:ti,ab,kw OR vardenafil:ti,ab,kw

#16 'tricyclic antidepressant agent'/de OR 'amitriptyline'/de 

OR 'clomipramine'/de OR 'desipramine'/de OR 'dosulepin'/de 

OR 'doxepin'/de OR 'imipramine'/de OR 'iprindole'/de 

OR 'lofepramine'/de OR 'nortriptyline'/de OR 'opipramol'/de 

OR 'protriptyline'/de OR 'trimipramine'/de

108,601

#15 ((antidepress*:ti,ab,kw OR 'anti depress*':ti,ab,kw OR '5

hydroxytryptophan':ti,ab,kw OR amisulpride:ti,ab,kw 

OR bupropion:ti,ab,kw OR citalopram:ti,ab,kw 

OR escitalopram:ti,ab,kw OR fluoxetine:ti,ab,kw 

OR fluvoxamine:ti,ab,kw OR maprotiline:ti,ab,kw 

OR mianserin:ti,ab,kw OR paroxetine:ti,ab,kw OR quipazine:ti,ab,kw 

OR ritanserin:ti,ab,kw OR sulpiride:ti,ab,kw OR trazodone:ti,ab,kw 

OR tryptophan:ti,ab,kw OR 'venlafaxine hydrochloride':ti,ab,kw 

OR viloxazine:ti,ab,kw OR ssri:ti,ab,kw OR ssris:ti,ab,kw OR 'selective

serotonin reuptake':ti,ab,kw OR 'selective serotonin re-uptake':ti,ab,kw 

OR snri:ti,ab,kw OR snris:ti,ab,kw OR serotonin:ti,ab,kw) 

AND 'noradrenaline reuptake inhibitor':ti,ab,kw OR serotonin:ti,ab,kw) 

AND 'noradrenaline reuptake inhibitors':ti,ab,kw OR nri:ti,ab,kw 

OR nris:ti,ab,kw OR 'norepinephrine reuptake inhibitor':ti,ab,kw 

OR 'norepinephrine reuptake inhibitors':ti,ab,kw

5,610

#14 'antidepressant agent'/de OR 'serotonin uptake inhibitor'/de 

OR 'serotonin noradrenalin reuptake inhibitor'/de OR 'adrenergic

receptor affecting agent'/de OR '5 hydroxytryptophan'/de 

OR 'amisulpride'/de OR 'amfebutamone'/de OR 'citalopram'/de 

OR 'fluoxetine'/de OR 'fluvoxamine'/de OR 'maprotiline'/de 

OR 'mianserin'/de OR 'paroxetine'/de OR 'quipazine'/de 

OR 'ritanserin'/de OR 'sulpiride'/de OR 'trazodone'/de 

OR 'tryptophan'/de OR 'venlafaxine'/de OR 'viloxazine'/de

252,721

#13 'cognitive behavior*':ti,ab,kw OR 'cognitive behaviour*':ti,ab,kw 

OR intervention:ti,ab,kw OR interventions:ti,ab,kw 

OR nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmac*:ti,ab,kw 

OR 'non pharmac*':ti,ab,kw OR pharmac*:ti,ab,kw 

OR program*:ti,ab,kw OR psych*:ti,ab,kw OR psychosocial:ti,ab,kw 

OR 'psycho social':ti,ab,kw OR rehabilitation:ti,ab,kw 

OR therapy:ti,ab,kw OR therapies:ti,ab,kw OR treat*:ti,ab,kw

10,743,323

#12 'behavior therapy'/de OR 'cognitive behavioral therapy'/de OR 'mental

health service'/de OR 'psychotherapy'/de OR 'psychosocial care'/de 

309,109
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OR 'social support'/de OR 'motivational interviewing'/de OR 'patient

participation'/de

#11 (checklist*:ti,ab,kw OR 'check list*':ti,ab,kw OR questionnaire:ti,ab,kw 

OR questionnaires:ti,ab,kw OR instrument:ti,ab,kw 

OR instruments:ti,ab,kw OR inventory:ti,ab,kw OR inventories:ti,ab,kw 

OR scale:ti,ab,kw OR scales:ti,ab,kw OR schedule:ti,ab,kw 

OR schedules:ti,ab,kw OR screen:ti,ab,kw OR screened:ti,ab,kw 

OR screening:ti,ab,kw OR 'beck depression':ti,ab,kw OR bdi:ti,ab,kw 

OR bdi2:ti,ab,kw OR 'geriatric depression scale':ti,ab,kw 

OR gds:ti,ab,kw OR 'hamilton rating scale for depression':ti,ab,kw 

OR 'hospital anxiety':ti,ab,kw) AND 'depression scale':ti,ab,kw 

OR hads:ti,ab,kw OR 'kidney disease quality of life':ti,ab,kw 

OR kdqol:ti,ab,kw OR 'medical outcomes study short form health

survey 36':ti,ab,kw OR 'mos sf36':ti,ab,kw OR 'minnesota multiphasic

personality inventory':ti,ab,kw OR mmpi:ti,ab,kw OR 'multiple affect

adjective check list':ti,ab,kw OR maacl:ti,ab,kw OR 'patient health

questionnaire':ti,ab,kw OR phq2:ti,ab,kw OR 'phq 2':ti,ab,kw 

OR phq9:ti,ab,kw OR 'phq 9':ti,ab,kw OR 'prime-md':ti,ab,kw 

OR 'epidemiologic studies depression scale':ti,ab,kw OR ced:ti,ab,kw 

OR cesd:ti,ab,kw OR bref:ti,ab,kw OR dass21:ti,ab,kw OR idid:ti,ab,kw 

OR 'quick inventory of depressive symptomatology self-report':ti,ab,kw 

OR 'qids sr':ti,ab,kw OR 'rand 36‐item health survey':ti,ab,kw OR 'rand

36':ti,ab,kw OR 'short form 36':ti,ab,kw OR 'sf 36':ti,ab,kw 

OR 'structured clinical interview':ti,ab,kw OR scid:ti,ab,kw OR 'selfrating depression scale':ti,ab,kw OR sds:ti,ab,kw OR 'short form health

survey 36':ti,ab,kw OR sf36:ti,ab,kw

219,556

#10 'brief psychiatric rating scale'/de OR 'diagnostic procedure'/de 

OR 'neuropsychological test'/de OR 'patient health questionnaire'/de 

OR 'psychological rating scale'/de OR 'psychologic test'/de 

OR 'questionnaire'/de

825,223

#9 #5 AND #8 8,835

#8 #6 OR #7 773,952

#7 depressed:ti,ab,kw OR depressive:ti,ab,kw OR depression*:ti,ab,kw 

OR suicidal:ti,ab,kw OR suicide:ti,ab,kw OR suicides:ti,ab,kw

620,970

#6 'depression'/exp 459,806

#5 #1 OR #2 OR #3 OR #4 445,287

#4 dialysis:ti,ab,kw OR haemodiafiltration:ti,ab,kw 

OR hemodiafiltration:ti,ab,kw OR 'haemo diafiltration':ti,ab,kw 

OR 'hemo diafiltration':ti,ab,kw OR haemofiltration:ti,ab,kw 

OR hemofiltration:ti,ab,kw OR 'haemo filtration':ti,ab,kw OR 'hemo

filtration':ti,ab,kw OR haemodialysis:ti,ab,kw OR hemodialysis:ti,ab,kw 

OR 'haemo dialysis':ti,ab,kw OR 'hemo dialysis':ti,ab,kw

206,562
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#3 'hemodialysis'/exp OR 'hemofiltration'/exp OR 'hemodiafiltration'/exp 

OR 'peritoneal dialysis'/exp

140,123

#2 (((chronic OR endstage OR 'end stage' OR endstate OR 'end

state' OR failure OR 'long term' OR maintenance) NEAR/2 

(kidney OR renal)):ti,ab,kw) OR eskd:ti,ab,kw OR eskf:ti,ab,kw 

OR esrd:ti,ab,kw OR esrf:ti,ab,kw

259,194

#1 'chronic kidney failure'/exp 136,333

EBM Reviews: 

Cochrane Central Register of Controlled Trials April 2019 

Cochrane Database of Systematic Reviews 2005 to May 2, 2019 

Database of Abstracts of Reviews of Effects 1st Quarter 2016

Health Technology Assessment 4th Quarter 2016

Date searched: May 16, 2019 

# Searches Results

1 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or 

maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab.

18139

2 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or 

haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or 

hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab.

16708

3 or/1-2 28646

4 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 70284

5 and/3-4 564

6 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or 

inventory or inventories or scale or scales or schedule or schedules or screen or screened or 

screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or 

"Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or 

"Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health 

Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple 

Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or 

PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or 

BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or 

QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or 

"Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form 

Health Survey 36" or SF36).ti,ab.

286914
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7 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or nondrug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or 

psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab.

1033100

8 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram 

or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or 

Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or 

Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or 

SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and 

Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or 

"norepinephrine reuptake inhibitors").ti,ab.

23770

9 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or 

Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or 

Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab.

10032

10 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab. 4995

11 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 

(program* or therap* or train*)) or cross-training).ti,ab.

29280

12 music therapy.ti,ab. 1091

13 or/6-12 1100240

14 and/5,13 533

ClinicalTrials.gov 

Date searched: May 16, 2019 

( depressed OR depressive OR depression* OR suicidal OR suicide OR suicides ) AND 

INFLECT EXACT ( "Active, not recruiting" OR "Completed" OR "Suspended" OR 

"Terminated" OR "Withdrawn" OR "Unknown status" ) [OVERALL-STATUS] AND ( ( 

chronic OR endstage OR end-stage OR failure ) AND ( kidney OR renal ) OR ESKD OR 

ESKF OR ESRD OR ESRF OR dialysis OR haemodiafiltration OR hemodiafiltration OR 

haemo-diafiltration OR hemo-diafiltration OR haemofiltration OR hemofiltration OR 

haemo-fi ) [DISEASE] = 83 results

WHO ICTRP

Date searched: May 16, 2019 

(((chronic OR endstage OR end-stage OR failure) AND (kidney OR renal)) OR ESKD OR 

ESKF OR ESRD OR ESRF) AND (depress* OR suicid*) = 7 trials
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VA HSR&D

https://www.hsrd.research.va.gov/research/

Date searched: May 16, 2019 

Separately searched terms: kidney and renal. Reviewed result lists = 0 studies found. 
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APPENDIX B. STUDY SELECTION

Inclusion/Exclusion Criteria for Full Text Review

1. Language: Is the full text of the article in English? 

Yes.............................................................................................................................Proceed to #2

No ..............................................................................................................Code X1. STOP

2. Population: Does the study include adults with ESRD or CKD (or CKF, CRF) undergoing 

maintenance dialysis?

Yes ............................................................................................Proceed to #3

No ......Code X2. Add code B (example: X2 – B) if retaining for background/discussion. STOP

3. Population: Does the study include adults screened, diagnosed with, or treated for depression?

Yes....................................................................................................................Proceed to #4

No... ..........................Code X2. Add code B if retaining for background/discussion. STOP

4. KQ1: Does the study examine screening tool(s) for depression? 

Yes...................................................................................................................Proceed to Q5

No ...........................................................................Code 0 for KQ1. Proceed to Q6

5. KQ1: Does the study compare a screening tool against the gold standard (eg, clinical interview – 

eg, SCID) or another validated depression assessment tool?

Yes, gold standard (eg, clinician interview/SCID)...Code I for "I or X Code" and 1 for KQ1. 

STOP

Yes, another depression tool...............Code I for "I or X Code" and 1 - Tool for KQ1. STOP

No .....................................................................Proceed to Q6 (and code 0 for KQ1) 

6. Study Design: Is the study original quantitative research, a systematic review (SR) or metaanalysis (MA; exclude other literature reviews, editorials, qualitative research, etc.)?

Yes................................................................................... If SR or MA code X3 - PEARL.

If other quantitative, Proceed to Q7

No.......Code X3. Add code B (example: X3 – B) if retaining for background/discussion. Code 0

for all KQs. STOP

7. Comparator: The study has a comparison group (other screening tool, no screening, other 

intervention, waitlist controls, etc.). Pre-post studies are excluded. 

Yes ............................................................................................ Proceed to Q8

No......Code X4. Add code B if retaining for background/discussion. Code 0 for all KQs STOP

8. Outcomes: Does the study report 1 or more of the following outcomes specifically for the 

population of interest (ESRD/CKD maintenance dialysis) Diagnostic test performance:

sensitivity, specificity, positive predictive value, and negative predictive value; Therapeutic 

impact: timing, setting, or type of treatment.; Intermediate and Patient outcomes: depressive 

symptoms, mortality, suicide attempts or completion, hospitalization, ED/urgent care utilization, 

patient satisfaction, adherence to dialysis, medication, or treatment, pain medication reduction, 

BP/metabolic control, quality of life, other outcomes (eg, employment); Adverse effects or 

unintended consequences. Prevalence and correlational studies are excluded.

Yes ...............................................................................................Proceed to Q9
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No.......Code X5. Add code B if retaining for background/discussion. Code 0 for all KQs STOP

9. Does the article or main study (from which the data were gathered) examine the impact of 

screening or the effectiveness of treatment for depression (including subgroup differences or 

harms)?

Yes, screening ................................................................................Proceed to Q10

Yes, treatment:

Is depression an inclusion criterion, or is the average depression score of participants 

equivalent to at least moderate depression? (Cutoffs: PHQ-9 ≥ 10;16 CES-D ≥ 18;17

HAM-D ≥ 12;18 BDI-II ≥ 16;17,18 BDI-II ≥ 13;18 HADS ≥ 819,20) 

No.............................................................................................Code X2 

Yes....................................................................................Proceed to Q10

No ...............................Code X5. Add code B if retaining for background/discussion. STOP

10. Harms: Does the article examine the harms of screening or treatment?

Yes........................................Code I for "I or X Code" and 1 for KQ4. Proceed to Q11.

No........................................................................Code 0 for KQ4. Proceed to Q11.

11. Study Design: Does the article describe data collected as part of an RCT or NRCT? 

Yes............................................................................................Proceed to Q12.

No.................................................................Code X3. Code 0 for KQs 2, 3. STOP.

12. KQs 2 and 3: Does the study examine the impact of screening or treatment?

Yes....................................Code I for "I or X Code" and 1 for KQ2 if screening and/or

1 for KQ3 if treatment. Code 0 for KQ 2 or 3 if NA. STOP. 

No.........................................................................Code 0 for KQs 2 and 3. STOP.

All articles should have at least 1 code. If not, re-review. Be sure that all articles are coded 0 for 

all KQs that are not relevant.
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APPENDIX C. QUALITY AND APPLICABILITY ASSESSMENT OF DIAGNOSTIC STUDIES 

Abbreviations: N = no; NA = not applicable; ROB = risk of bias; U = unclear; Y = yes

*Questions (QUADAS-225):

1. Consecutive or random sample of patients enrolled? 

2. Was a case-control design avoided? 

3. Did the study avoid inappropriate exclusions? 

4. Was the index test interpreted without knowledge of the reference standard results? 

5. Was staff trained in the use of the index test? 

6. Was the fidelity of the index test monitored and/or reported? 

7. Is the reference standard likely to correctly classify the target condition? 

8. Was the reference standard interpreted without knowledge of the index test results? 

Rating Criteria*

Study

Could the selection 

of patients have 

introduced bias?

Could the conduct or 

interpretation of the 

index test have 

introduced bias?

Could the conduct or 

interpretation of the 

reference standard have 

introduced bias?

Could the patient flow 

have introduced bias? Applicability

1 2 3 ROB 4 5 6 7 ROB 8 9 10 11 ROB 12 13 14 ROB 15 16 17 ROB

Alsuwaida, 200652 U Y U Unclear Y U U Y Unclear Y Y U Y Unclear Y NA U Unclear N N N Low

Balogun, 201139 U Y Y Unclear Y U U Y Unclear Y U U U Unclear Y Y N High N N N Low

Bautovich, 201848 U Y Y Unclear Y U NA Y Unclear Y Y N Y High Y NA Y Low N N N Low

Chilcot, 200853 U Y Y Unclear U U NA Y Unclear U Y U U Unclear Y NA Y Low N N N Low

Collister, 201949 Y Y Y Low U U U Y Unclear U U U U Unclear Y NA Y Low N N N Low

Gencoz, 200742 Y Y U Unclear Y Y Y Y Low Y U Y U Unclear Y Y Y Low N N N Low

Giordano, 200740 Y U Y Unclear U Y Y Y Unclear Y Y U Y Unclear Y NA N High N N N Low

Grant, 200850 U Y Y Unclear U U NA Y Unclear U Y U Y Unclear Y NA Y Low N N N Low

Hedayati, 200633 U Y Y Unclear Y U NA Y Unclear U Y U Y Unclear Y NA Y Low N N N Low

Loosman, 201035 U Y Y Unclear Y U NA Y Unclear Y Y Y Y Low Y NA Y Low N N N Low

Neitzer, 201246 U Y Y Unclear U U NA Y Unclear U U NA Y Unclear Y NA Y Low N N N Low

Preljevic, 201236 U Y Y Unclear Y U NA Y Unclear Y U Y Y Unclear Y NA N Low N N N Low

Troidle, 200347 Y Y Y Low N U U Y High U U U U Unclear Y NA Y Low N N N Low

Van den Beukel, 

201251

U Y Y Unclear U U U Y Unclear U U U Y Unclear Y NA Y Low N N N Low

Wang, 201945 Y Y Y Low Y U U Y Unclear Y U U Y Unclear Y NA Y Low N N N Low

Watnick, 200544 U Y Y Unclear Y U NA Y Unclear Y Y U Y Unclear Y NA Y Low N N N Low
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9. Was staff trained in the assessment of the reference standard? 

10. Was the fidelity of the reference test monitored and/or reported? 

11. Was there an appropriate interval between the index test and reference standard? 

12. Did all patients receive the same reference standard?

13. If a partial selection of patients received the reference standard, was it adjusted? 

14. Were all patients included in the analysis? 

15. Are there concerns that the study population differs from the review question? 

16. Are there concerns that the index test, its conduct, or its interpretation differ from the review question? 

17. Are there concerns that the reference standard, its conduct, or its interpretation differ from the review question?
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APPENDIX D. QUALITY AND APPLICABILITY ASSESSMENT OF RANDOMIZED CONTROLLED 

TRIALS 

Author, Year

Rating Criteria*

Funding source

Overall 

Quality 

Rating

Applicabilit

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 y

Al Saraireh, 2018 68 Y NR N NA Y U U N Y N Y N Y U Y NA N Investigator Poor Fair

Babamohamadi, 

201779 NR NR N U Y U U N Y N U N Y Y U U N NR Poor Poor

Beizaee, 201875 Y Y Y Y Y Y Y N Y N Y N N U Y NA Y University Fair Fair

Blumenfield, 199760 NR Y U U N U Y Y Y N N N Y U Y N N Industry grant Poor Fair

Cukor, 201469 NR NR Y U Y Y Y Y Y N N Y Y U Y N N NIDDK Fair Fair

Duarte, 200967 Y Y N U Y Y Y Y Y N N Y Y Y Y N N Government Fair Fair

Friedli, 201761 Y Y Y N Y Y Y Y Y Y N N Y U Y N N NIH grant Fair Good

Gharekhani, 201466 Y U Y N Y N N Y Y Y N N Y Y Y N N University Poor Good

Heshmatifar, 201573 NR NR Y U Y U U N Y N N Y Y U U N U NR Poor Fair

Hosseini, 201264 U NR Y Y Y U U N Y N N Y Y U Y N N Government Poor Fair

Kalani, 201971 N U Y U Y U U U Y U Y N Y Y Y U N University Poor Fair

Kouidi, 201074 NR NR Y U Y U U N Y N N Y Y U Y N N NR Poor Fair

Lerma, 201770 Y NR Y U Y Y Y N Y N N N Y Y Y N N Government Fair Fair

Mehrotra, 201963

Y Y U Y Y Y N N Y N Y N Y Y Y Y N Government, University,

NIDDK, DCI Fair Fair

Rahimipour, 201576 U NR U U Y U U U N U U U Y U Y U N NR Poor Fair

Taraz, 201362 Y U Y Y Y U U Y Y N N N Y Y Y N N University grant Fair Good

Thomas, 201778 Y NR N U Y Y U N Y N Y N Y Y Y N N University grant Fair Fair

Tsay, 200472 NR NR Y U Y U U N Y N N Y Y U Y N N Government Poor Fair

Wang, 201665 Y Y Y Y Y U Y Y Y N N U Y Y Y N N NR Fair Poor

Widyaningrum, 2013

77 NR NR Y U Y U U U N U U U Y U Y U N NR Poor Poor

Abbreviations: DCI = Dialysis Clinic Inc.; N = no; NA = not applicable; NIDDK = National Institute of Diabetes and Digestive and Kidney Diseases; NR = not reported; U = 

unclear; Y = yes

*Quality Rating Criteria:

1. Randomization adequate? 

2. Allocation concealment adequate? 

3. Groups similar at baseline? 
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4. Maintain comparable groups? 

5. Eligibility criteria specified? 

6. Outcome assessors masked? 

7. Care provider masked? 

8. Patient masked? 

9. Reporting of attrition, crossovers, adherence, and contamination? 

10. Important differential loss to follow-up or overall high loss to follow-up?

11. Intention-to-treat (ITT) analysis? 

12. Post-randomization exclusions? 

13. Were outcomes pre-specified and defined, and ascertained using accurate methods? 

14. Intervention fidelity? 

15. Follow-up long enough for outcomes to occur? (minimum 4 weeks for drugs) 

16. Appropriate handling of missing data? 

17. Evidence of selective outcome reporting? 
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APPENDIX E. ADVERSE EVENTS REPORTED IN DEPRESSION TREATMENT TRIALS IN 

PATIENTS WITH END-STAGE RENAL DISEASE

Blumenfield, 199760 Friedli, 201761* Mehrotra, 201963 Taraz, 201362†

Severity System Adverse Event

Fluoxetine 

(N = 6)

Placebo 

(N = 7)

Sertraline

(N = 15)

Placebo 

(N = 15)

CBT (N 

= 60)

Sertraline 

(N = 60)

Sertraline 

(N = 21)

Placebo 

(N = 22)

NonSerious

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Autonomic Dry mouth 0 1 --- --- --- --- --- ---

Cardiovascular

 

 

Cardiac unspecified --- --- --- --- 3 9 --- ---

Hypotension 4 1 --- --- --- --- --- ---

Palpitations --- --- 1 0* --- --- --- ---

Gastrointestinal

 

 

 

 

 

 

 

Abdominal pain 1 2 --- --- --- --- --- ---

Constipation 0 1 --- --- --- --- --- ---

Diarrhea 1 1 --- --- --- --- --- ---

Dyspepsia 1 0 --- --- --- --- 6 4 

Gastro-enteritis 0 2 --- --- --- --- --- ---

Gastrointestinal unspecified --- --- --- --- 11 22 --- ---

Nausea 5 2 1 0* --- --- 7 3

Vomiting 3 3 --- --- --- --- --- ---

Musculoskeletal Myalgia 1 1 --- --- --- --- --- ---

Neurological

 

 

 

 

 

Dizziness 1 0 1 0* --- --- 5 3

Headache 3 0 1 0* --- --- 4 2

Insomnia 2 1 1 0* --- --- --- ---

Nervous system unspecified --- --- --- --- 0 8 --- ---

Sensation disturbance 1 0 --- --- --- --- --- ---

Tremors 1 0 --- --- --- --- --- ---

Psychiatric

 

 

 

Abnormal thought 1 0 --- --- --- --- --- ---

Anorexia --- --- --- --- --- --- 2 4

Anxiety 0 1 --- --- --- --- --- ---

Nervousness 1 1 --- --- --- --- --- ---
ESRD and Depression Evidence Synthesis Program

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Respiratory

 

 

 

 

 

Bronchitis 1 0 --- --- --- --- --- ---

Cough 0 2 --- --- --- --- --- ---

Dyspnea 1 0 --- --- --- --- --- ---

Pharyngitis 1 0 --- --- --- --- --- ---

Rhinitis 1 0 --- --- --- --- --- ---

Upper respiratory tract 

infection 1 0 --- --- --- --- --- ---

Skin

 

 

 

Furunculosis 1 0 --- --- --- --- --- ---

Pruritus 1 0 --- --- --- --- --- ---

Skin ulcer 0 1 --- --- --- --- --- ---

Sweating --- --- 1 0* --- --- --- ---

Other

 

 

 

 

 

 

Dehydration 0 1 --- --- --- --- --- ---

Edema 0 1 --- --- --- --- --- ---

Flu syndrome 1 0 --- --- --- --- --- ---

Hair Loss --- --- --- --- --- --- 1 1

Other unspecified --- --- --- --- 3 17 --- ---

Sexual dysfunction --- --- --- --- --- --- 2 1

Tooth infection 1 0 --- --- --- --- --- ---

Serious

 

 

 

 

Gastrointestinal Gastrointestinal unspecified --- --- --- --- 1 1 --- ---

Cardiovascular Cardiac unspecified --- --- --- --- 4 4 --- ---

Other

 

 

Death --- --- 1 0 2 0 --- ---

Major bleeding --- --- --- --- 1 2 --- ---

Other unspecified --- --- --- --- 2 9 --- ---

*The events reported in this table are only those that resulted in study dropout. There were other adverse events reported narratively, but it was not clear from the text which 

category or study arm they occurred in, so they are not recorded in this table.

†

It is unclear whether the events of study dropouts were included in these totals. There was 1 death in each group and some attrition due to AEs, but the dropouts were not analyzed 

in this per-protocol study.
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APPENDIX F. PEER REVIEW COMMENTS/AUTHOR RESPONSES 

Reviewer 

Number

Reviewer Comment Author Response

Are the objectives, scope, and methods for this review clearly described?

2 Yes Thank you.

3 Yes Thank you.

5 Yes Thank you.

6 Yes Thank you.

Is there any indication of bias in our synthesis of the evidence?

2 No Thank you.

3 No Thank you.

5 No Thank you.

6 No Thank you.

Are there any published or unpublished studies that we may have overlooked?

2 No Thank you.

3 No Thank you.

5 No Thank you.

6 No Thank you.

Additional suggestions or comments can be provided below. If applicable, please indicate the page and line numbers from the draft report.

3 Minor: Amend page "iv" of Table of Contents (line 59) to include

KQ3: Effectiveness of Depression Treatment in Patients with ESRD and 

Depression

Thank you. We have resolved this omission.

5 This report is thorough, and unfortunately comprehensive. I say 

'unfortunately comprehensive' because this highlights the lack of 

research in the area.

I think it is critical for the VA to fund studies to consider not only 

screening and treatment, but also the potential sequelae and resources 

available to address a large number of positive screening tests. This 

work is not to be underestimated, as tremendous resources would need 

to be employed at local facilities where screening may occur, given the 

high rates of depressive symptoms in patients on dialysis.

Thank you.
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5 I have now read through the entire report, but do not have time today to 

write more extensively on the details within the report.

I would urge the team to include more details about treatment in the 

executive summary. A table about screening is including in that initial 

summary. I think it would serve the future readers well to have a similar 

summary of the findings on treatment in this population. Most readers 

will not have time to review the entire 80+ page report.

Thank you. We have added a table to both the 

executive summary and the discussion. 

5 Page 1, line 2 'tools' not 'tool'. Thank you, corrected.

5 Page 6, line 14 'United States' not 'United State'. Thank you, corrected.

6 

Overall, I think that this VA ESP systematic review is very 

comprehensive and organized. It will be an invaluable report and 

resource for VA. Congratulations to the team.

Thank you. 

6 1. executive summary (p.1, line 2). It should be tools and not tool Thank you, corrected.

6 2. executive summary (p.1, line 6). I would provide also the start date for 

the electronic database search

Thank you, revised.

6 

3. executive summary, results. I would consider reorganizing the results 

with subcategories for each question - KQ1 to KQ6. Since this is a 

summary, many readers will not review the remainder of the document 

and will be unaware of the items addressed. Therefore, I think it is 

important to include each question and the results for each. Currently, 

KQ2, KQ4, and KQ5 are not addressed in this section.

Thank you, revised.

6 

4. Throughout the report, kidney is preferred to be used instead of renal We have replaced renal with kidney in cases that aren’t 

proper nouns, diagnoses, etc. (eg, we replaced renal 

failure with kidney failure).

6 

5. p. 8 - I could not understand what the circles with number are 

referring to. Please elaborate

Thank you. We have added a footnote: “Note. 

Associated key questions are noted in the shaded 

circles.” 

6 

6. p. 9 - the comparators row should be revised b/c no screening or 

other screening tool is not the comparator for all of the studies for the 

questions

Thank you! Revised.

6 7. p. 13 - please footnote and provide definitions for patient selection, 

index test, reference test, and flow and timing

Thank you. We added a footnote referencing Appendix 

C.

6 8. Table 2 - under the column "study setting sample characteristics and 

demographics" - please list the characteristics/criteria throughout and 

Thank you. Edited.
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report as NR if not reported. This provides a better sense of what was 

missing

6 

9. Page 28 - as above, the lack of studies addressing KQ2 is significant 

and should be reported in the executive summary. Please also state 

here whether there are any ongoing studies addressing this topic.

Thank you. We added this to the executive summary. 

We did not identify any ongoing studies addressing this 

topic. Our database search includes PubMed, in which 

ClinicalTrials.gov trials are indexed.

6 

10. Table 8 - please footnote and define "quality" - how it was 

determined and the criteria used to make such determination. I think you 

could cite appendix C and D

Thank you. We have added a reference to Appendix D 

in the footer.

6 11. Table 9 - please footnote and define meaning of "k" that is included 

throughout the table

Thank you, we have added definitions for both k and n 

to the footer. 

6 12. Table 9 - please footnote and define "strength of evidence" - how it 

was determined and the criteria used to make such determination.

Thank you. This information is in the footer. We have 

reorganized it for clarity.

6 13. p. 51 - if available, would list frequencies of adverse events Thank you. We have added a table to with reported AE 

frequencies to the appendix. 

6 

14. Discussion. P. 53 - as with the executive summary, I would consider 

organizing the discussion around the KQs so that when one reads the 

summary, they are aware of all of the domains addressed.

Thank you, to insure all key questions are addressed in 

the discussion, we have added a statement that there 

were no studies found examining outcomes related to 

screening.

6 

15. Discussion, p. 53 - I would elaborate upon how the populations 

studies bear little resemblance to Veterans. Is it differences in age, race, 

SES, etc? Also, how might this limit generalizability of the findings from 

studies?

Thank you, we have updated this section.

6 16. Discussion, p. 53, line 30. "positive predictive value is less than 

ideal" - please elaborate on what is considered "ideal"

Thank you. We clarified this.

6 17. Discussion, p. 54, line 24. would give an example of a short 

screening tool

Thank you. The next sentence in that paragraph 

provides an example (ie, BDI-FS).

6 

18. Discussion. I would elaborate on the difference between quality of 

evidence and strength of evidence.

Thank you. We did not distinguish these differences in 

the discussion. However, these concepts are described 

in detail in Methods and Appendices.

6 19. p. 55, line 3 - spell out "ROB" Thank you, edited.

6 20. I would consider including in "research gaps/future research" section 

the opportunity to explore the unaddressed questions (e.g,, KQ2, etc.)

Thank you. We have edited this section.