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 end-
stage 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
7.1
a
0.88
13.5
b
0.32
22.8
c
0.47
33.0
d
0.59
39.3
e
0.66
Watnick, 2005
N = 62
19.4%, NR
BDI 16
91 86
7.1
a
0.33
13.5
b
0.50
22.8
c
0.66
33.0
d
0.76
39.3
e
0.81
Chilcot, 2008
N = 40
22.5%; 30-
32.5%
BDI 16
88.9 87.1
7.1
a
0.35
13.5
b
0.52
22.8
c
0.67
33.0
d
0.77
39.3
e
0.82
Grant, 2008
N = 57
12.3%; 31.6%
BD I15
100 78
7.1
a
0.26
13.5
b
0.42
22.8
c
0.57
33.0
d
0.69
39.3
e
0.74
Patient Health Questionnaire 9 (PHQ-9)
Watnick, 2005
N = 62
19.4%, NR
PHQ-910
92 92
7.1
a
0.47
13.5
b
0.64
22.8
c
0.77
33.0
d
0.85
39.3
e
0.88
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
MontgomeryÅsberg 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
14
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
15
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. pharmaco-
l
ogical?
b. non-pharmaco-
logical?
c. pharmacological
and non-
pharmacological
treatments
combined
KQ4: In patients
with ESRD, what
are the potential
harms of:
a. screening?
b.
treatment for
depressed
patients?
i. Pharmaco-
logical?
ii. non-pharmaco-
logical?
KQ5: Do the benefits or
harms of screening
differ by:
a. patient
ch
aracteristics 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
ch
aracteristics 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 ≥ 8
19,20
)
a. Adults with ESRD
b. 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 ≥ 8
19,20
)
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 non-
pharmacological
treatments for depression
Comparators
Clinical
evaluation,
Other
screening
tools.
Exclude DSM-
II
I and earlier
No screening, other
screening tool
Placebo, waitlist
control, other
intervention
a. No screening,
other screening
tool
b. Placebo, waitlist
c
ontrol, other
intervention
No screening, other
screening tool
Placebo, waitlist control,
other intervention
ESRD and Depression Evidence Synthesis Program
16
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. pha
rmaco-
logical?
b. non-pharmaco-
logical?
c. pharmacological
and non-
pharmacological
treatments
combined
KQ4: In patients
with ESRD, what
are the potential
harms of:
a. s
creening?
b. treatment for
depressed
patients?
i. Pharmaco-
logical?
ii. non-pharmaco-
logical?
KQ5: Do the benefits or
harms of screening
differ by:
a. p
atient
characteristics or
other social
determinants of
health?
b. setting?
c. screening
characteristics/
process?
d. other (eg, patient
engagement/
receptivity to
treatment, social
support)?
e. ti
ming and type of
follow up?
KQ6: Do the benefits or
harms of treatment differ
by:
a. p
atient
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. ti
ming 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. pha
rmaco-
logical?
b. non-pharmaco-
logical?
c. pharmacological
and non-
pharmacological
treatments
combined
KQ4: In patients
with ESRD, what
are the potential
harms of:
a. s
creening?
b. treatment for
depressed
patients?
i. Pharmaco-
logical?
ii. non-pharmaco-
logical?
KQ5: Do the benefits or
harms of screening
differ by:
a. p
atient
characteristics or
other social
determinants of
health?
b. setting?
c. screening
characteristics/
process?
d. other (eg, patient
engagement/
receptivity to
treatment, social
support)?
e. ti
ming and type of
follow up?
KQ6: Do the benefits or
harms of treatment differ
by:
a. p
atient
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. ti
ming 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 = End-
stage 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
ESRD and Depression Evidence Synthesis Program
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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-2
25
and the Newcastle-Ottawa Scale
26
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.
ESRD and Depression Evidence Synthesis Program
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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.
ESRD and Depression Evidence Synthesis Program
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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).
ESRD and Depression Evidence Synthesis Program
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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 (BDI-
II).
27
Other tools include the Cognitive Depression Index (CDI
31
; 4 studies), the Center for
Epidemiologic Studies – Depression Scale (CES-D
32
; 1 study
33
), the Hospital Anxiety and
Depression Scale - Depressive Subscale (HADS-D
34
; 2 studies
35,36
), the Geriatric Depression
Scale-15 (GDS-15
37,38
; 2 studies
39,40
), the Hamilton Depression Rating Scale (Ham-D
41
; 1
study
42
), the Patient Health Questionnaire 9 (PHQ-9
43
; 1 study
44
), 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 [DI-
MHD]).
45
Table 2 provides study characteristics.
Five studies
33,39,44,46,47
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 8.5
36
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
ESRD and Depression Evidence Synthesis Program
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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.
ESRD and Depression Evidence Synthesis Program
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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
re
gion,
years of
enrollment
Study setting
Sample
char
acteristics and
demographics
Inclusion Criteria/ Exclusion
Criteria
Index Test(s);
Administration
Reference Standard;
Administration
% MDD Positive
per Index Test;
Reference
Standard
Alsuwaida,
2006
52
N = 26
Saudi Arabia
Single Site: hospital-
based 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
psy
chiatric 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,
2011
39
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
ill
ness [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:
BDI10= 37.1%,
GDS-15 5 =
32.3%;
30.6%
Bautovich,
2018
48
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%
ESRD and Depression Evidence Synthesis Program
25
Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics 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,
2008
53
N = 40
UK
Multisite: outpatient
renal service
40% Female
A
ge: 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
t
han 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-I
I (ref for CDI):
Self-report. Same day as the CDI.
BDI16 on
dialysis = 32.5%,
off dialysis =
30%, CDI10 on
and off dialysis =
32.5%; 22.5%
1
Collister,
2019
49
N = 50
Canada
Multisite: outpatient
HD units
48% Female
A
ge: 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
s
tudy 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;
HADS7=54%
ESRD and Depression Evidence Synthesis Program
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Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics and
demographics
Inclusion Criteria/ Exclusion
Criteria
Index Test(s);
Administration
Reference Standard;
Administration
% MDD Positive
per Index Test;
Reference
Standard
1
Gencoz,
2007
42
N = 45
Turkey
Single site: hospital-
based outpatient HD
unit
42.2% Female
A
ge: 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
i
mpairment 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
1
Giordano,
2007
40
N = 31
Italy
Single site: hospital-
based HD unit
35.5% Female
A
ge: 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%
ESRD and Depression Evidence Synthesis Program
27
Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics and
demographics
Inclusion Criteria/ Exclusion
Criteria
Index Test(s);
Administration
Reference Standard;
Administration
% MDD Positive
per Index Test;
Reference
Standard
2
Grant,
2008
50
N = 57
UK
Single site:
outpatient HD unit
29.8% Female
A
ge: 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 ICD-
10 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%
BD
I-II 15 =
31.6%;
1
Hedayati,
2006
56
N = 98
US
Durham, NC
March 2003-
April 2004
Multi-site: outpatient
dialysis units (VA, 2
non-VA)
44.9% Female
A
ge: 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
BDI14 = 30.6%,
CESD 18 =
30.6%; 26.5%
17
.3% MDD
1
Loosman,
2010
35
N = 62
Amsterdam
Feb-June
2008
Single site: hospital-
based HD and
outpatient PD
46.8% Female
A
ge: 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
t
o 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/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics 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
depr
ession: 9.7%
Antidepressants:
3.2%
Neitzer,
2012
46
N = 134
US
CA, TX
2009
Multisite: outpatient
HD units
48% Female
A
ge: 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%
1
Preljevic,
2012
36
N = 109
Norway
Multisite: hospital-
based HD and PD
centers
30.3% Female
A
ge 57.8(15.7)
Race: NR
69.4% HS or less
HD: 76.6%; PD:
23.3%
Months on dialysis:
M=8.5 (3.7522)
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,
ps
ychosis 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
BDI16 = 20.8%,
CDI11 = NR,
HADS-D8 =
20.1%; 22%
14.
7% MDD
ESRD and Depression Evidence Synthesis Program
29
Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics 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
1
Troidle,
2003
47
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 SF-
36:
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
1
Van den
Beukel,
51
2012
N = 133
Netherlands
Multisite: outpatient
hospital-based
dialysis units
39% Female
A
ge: 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%, CDI10 =
23%
ESRD and Depression Evidence Synthesis Program
30
Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics 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,
2005
44
N = 62
US
Portland, OR
July 2003-
May 2004
Multisite: public and
private outpatient
HD and PD units
(including VA)
Female: 32%
A
ge: 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,
M
MSE 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%
1
Wang,
2019
45
N = 319
China
Multisite: hospital-
based HD units
31.4% Female
depr
essed; 43.78%
Female non-
depressed
Age: 49.4 (6.04)
depressed;
50.92(6.46) non-
depressed
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
i
mpairment, 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-I
I (ref for DI-MHD):
Same time as index test.
BDI19 = 20.7%,
DI-MHD25 =
20%; 21.9%
ESRD and Depression Evidence Synthesis Program
31
Author, Year
N enrolled
Country/ U
S
region,
years of
enrollment
Study setting
Sample
ch
aracteristics 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
32
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,
2011
39
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,
2018
48
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,
2008
53
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.
2
Grant,
2008
50
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
1
Hedayati,
2006
33
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).
1
Loosman,
2010
35
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.
1
Preljevic,
2012
36
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
1
Wang,
2019
45
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,
2005
44
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,
2018
48
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
33
Author, Year
N enrolled
Cuto
ff
Sen
s
(%)
Spe
c
(%)
PPV
(%)
NPV
(%)
AU
C Summary of Findings
1
Hedayati,
2006
33
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).
1
Preljevic,
2012
36
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)
1
Hedayati,
2006
33
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,
2011
39
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)
1
Gencoz,
2007
42
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)
1
Loosman,
2010
35
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.
1
Preljevic,
2012
36
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,
2005
44
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
34
Author, Year
N enrolled
Cuto
ff
Sen
s
(%)
Spe
c
(%)
PPV
(%)
NPV
(%)
AU
C Summary of Findings
Alsuwaida,
2006
52
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 non-
depressed 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; PHQ-
9 = Patient Health Questionnaire 9; PPV = Positive predictive value; Sens = sensitivity; Spec = specificity; SRQ =
Self-Reporting Questionnaire
ESRD and Depression Evidence Synthesis Program
35
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, SCID-
I).
39,44,48,50,53
Sample sizes ranged from N = 40
53
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
36
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
10
39,50
68
77
57
85
0.73
100
50
21.9
100
0.93
15
50
100
78
NR
NR
0.93
16
44,53
88.9
87.1
88.8
87
0.961
91
86
59
98
0.937
18
48
100
90
60
100
0.99
20
50
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 = 43
53
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
12
36
91
63
39
96
0.92
13
35,36
75
90.2
75
90.2
0.90
91
68
43
97
0.92
14
56,36
62
81
53
85
0.77
86
71
44
95
0.92
15
36,45
82
75
46
94
0.92
87
49
34
93
0.84
16
36,45
82
87
62
95
0.92
87
58
39
94
0.84
17
36,45
82
89
67
95
0.92
87
65
43
94
0.84
18
36,45
77
92
71
94
0.92
87
71
47
95
0.84
19
45
83
86
63
94
0.84
20
45
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
37
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 0.50
56
and 0.82,
36
specificity was 0.83
56
and 0.93,
36
and AUC was 0.76
56
and 0.89 (see Tables 2 and 3).
36
Of note, 1
study
36
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
38
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 (DI-
MHD; 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
39
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, 2012
46
N = 134
4
97.2
91.8
81.4
98.9
0.98
Reference standard:
BDI-II 16
Cognitive Depression Index (CDI)
Chilcot, 2008
53
N = 40
10
77.8
80.6
77.7
80.6
0.94
Reference standard:
BDI-II 16
Depression Inventory Maintenance Hemodialysis (DI-MHD)
1
Wang, 2019
45
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
1
Collister, 2019
49
N = 50
2
81
74
NR
NR
0.81
Reference standard:
HADS 6.
Geriatric Depression Scale-15 (GDS-15)
1
Giordano, 2007
40
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?”
1
Troidle, 2003
47
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?”
1
Troidle, 2003
47
N = 97
≤3
65
67
NR
NR
NR
Reference standard:
BDI-II 11.
Mental Health Inventory 5 (MHI5)
1
Van den Beukel,
2012
51
N = 133
66
67
78
NR
NR
0.82
Reference standard:
BDI-II 16 (66+) and
CDI10 (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; KDQOL-
36 = 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
40
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
RCT
60
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 RCT
65
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
42
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 (BDI-
II: 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
colleagues
63
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 RCTs
69,70
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
43
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
44
Table 7. Characteristics of randomized controlled trials of interventions for depression in ESRD outpatients
Author, Year
Intervention,
N enrolled
Country/US
regi
on, years
of enrollment
Study setting,
clinical
char
acteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ± SD, T
vs C
Pharmacological
Blumenfield,
1997
60
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, 2017
61
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 mont
hs 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,
CreutzfeldtJakob 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
45
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Gharekhani,
2014
66
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
A
ge: 56.8 ± 13.09 yrs
Included: Adults, TIW HD for at least 3 months and
all had same HD rx
Excluded: BDI-I
I<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,
2012
64
Citalopram
N = 44
Iran
Years NR
Single-site: hospital HD
center
55% female
A
ge: 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
46
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Mehrotra,
2019
63
Sertraline vs
CBT
N = 120
US: NM, TX,
WA
2017
Multisite (3 states): 41
dialysis facilities
Median time since
s
tarting 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 BDI-
II 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, 2013
62
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
47
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Wang, 2016
65
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, 44.5
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,
2018
68
CBT vs PSE
N = 130
Jordan, 2017
Multisite: 5 hospital
dialysis units
Dialysis duration: NR
~50% Female
A
ge: 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, 2017
79
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: u
sing 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
48
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Beizaee,
2018
75
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, 2014
69
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), HAM-
D (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, 2009
67
CBT
N = 90
Brazil, year NR
2 sites: dialysis units
HD: 3x/wk for 4 hrs avg.
63.4% Female
A
ge: 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
49
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Heshmatifar,
2015
73
Benson
Relaxation
Technique
N = 70
Iran, 2013
Single site: hospital HD
unit
HD: 3x/wk
18% Female
A
ge: 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, 2019
71
Acupressure
N = 96
Iran, 2011
3 sites: HD centers
44% Female
Age: 53.4±13.9
Race: NR
Education: 31% non-
literate
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, 2010
74
Exercise
training
N = 50
Greece, year
NR
Single site: hospital
renal unit
HD: 3x/wk for 4 hrs
41.6% Female
A
ge: 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
50
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Lerma, 2017
70
CBT
N = 60
Mexico City,
MX Year NR
2 sites: HD units
HD: 3x/wk for 3-4hrs
51.6% Female
A
ge: 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: B
DI-II > 29 points were referred for
appropriate psychiatric evaluation and care.
Depression diagnosis:
mild-moderate (BDI-II score
of 1029 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,
2015
76
Hope therapy
N = 50
Iran, year NR
Multi-site: hospitals
HD: 2-3x/wk for 4 hrs
48% Female
A
ge: 47.82 (15.12)
Race/Education/Employ
ment/ Insurance: NR
Included: 1865 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,
2017
78
MBSR
N = 41
Montreal,
Canada, 2016
Single site: hospital HD
unit
33% Female
A
ge: 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
i
deation/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
51
Author, Year
Intervention,
N enrolled
Country/US
re
gion, years
of enrollment
Study setting,
clinical
ch
aracteristics,
demographics
Inclusion Criteria/ Depression Diagnosis
Depression Screening
Tool(s) and their application
Baseline
Depression
Score
Mean ±
SD, T
vs C
Tsay, 2004
72
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-ex
tremity 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,
2013
77
Latihan Pasrah
Diri
N = 36
Java,
Indonesia,
2012
Single site: hospital HD
unit
HD: 2x/wk
61.1 % Female
A
ge: 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: t
aking 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 = MontgomeryÅsberg 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),
Dura
tion of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
PHARMACOLOGICAL
SSRIs vs control
Blumenfield,
1997
60
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 basel
ine
(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, 2017
61
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),
Dura
tion of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
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, 2013
62
Sertraline vs
placebo
25 vs 25
Tx = 12 weeks
F/U = 12 weeks
Sertraline: 100mg/day
(50mg/day for 1
st
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, 2012
64
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
54
Author, Year
N randomized
(T vs C),
Duration of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
management, and muscle
relaxation techniques.
Mehrotra, 2019
63
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,
2014
66
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 soft-
gel 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, 2016
65
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
55
Author, Year
N randomized
(T vs C),
Duration of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
Tx = 52 weeks
F/U = 52 weeks
vs 21.9 ± 5.4 to 20.8 ± 5.1; P
= 0.033
NON-PHARMACOLOGICAL
Al Saraireh,
2018
68
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,
2017
79
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
56
Author, Year
N randomized
(T vs C),
Duration of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
Beizaee, 2018
75
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, 2014
69
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
57
Author, Year
N randomized
(T vs C),
Duration of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
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, 2009
67
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
Quality
Depression
Other outcomes
KDQOL. Between groups
sig improvement in
burden of kidney disease,
quality of social
interaction, sleep, overall
health, and mental
component summary
dimensions.
Heshmatifar,
2015
73
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, 2019
71
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
59
Author, Year
N randomized
(T vs C),
Duration of
treatment and
follow-up
Intervention
description
Comparator description
Findings, Treatment vs Comparator
Quality
Depression
Other outcomes
the solidity and the
remaining 18 minutes
for pressing the 6 points
(3 minutes for each
point). average of 34
kg pressure
Kouidi, 2010
74
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-<