The report is a product of the VA/HSR Evidence Synthesis Program.

End-stage Renal Disease and Depression: A Systematic Review

The incidence and prevalence of end-stage renal disease (ESRD) in the United States have increased steadily over the past four decades. Veterans experience a higher burden of chronic kidney disease (CKD) and ESRD than the general population. In addition, patients with ESRD experience major depressive disorder (MDD) at three to more than six times that of the general US population, and Veterans experience MDD at more than twice the rate of the general US population. The Centers for Medicare and Medicaid Services’ (CMS) requires routine depression screening for patients with ESRD. However, due to the lack of system-wide screening tool requirements, there is wide variation in the tools used to initially screen for depression. In addition, there is no established standard guiding the treatment of patients with ESRD and comorbid MDD. 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 VA and community settings – and the subsequent depression treatment-related outcomes for Veterans in all US healthcare settings – is vital.

The purpose of this review was 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. Investigators with VA’s Evidence Synthesis Program (ESP) Center in Portland, OR searched the literature, including Ovid MEDLINE, PsycINFO, Elsevier EMBASE, and Ovid EBM Reviews Cochrane Database of Systematic Reviews from inception through April 2019. After reviewing 7,452 studies (149 articles received full text review), they included 20 randomized controlled trials (RCTs) and 16 diagnostic accuracy studies for this analysis.

Summary of Findings

There is limited research evaluating the diagnostic accuracy of most screening tools for depression in patients with ESRD, and the existing studies may not be generalizable to patients in the US, or to Veterans receiving care in VA settings. Moreover, screening and intervention studies suffer from limitations related to methodological quality or reporting. This review reports on several screening tools—

• 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.
• Cognitive Depression Index (CDI): The CDI 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.
• Hospital Anxiety and Depression Scale – Depression Subscale (HADS-D): The HADS-D is a widely-used 21-item scale that includes ratings of physical, cognitive, and affective symptoms of depression.
• 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.
• 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.
• 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.
• 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.
• Self-Reporting Questionnaire (SRQ): The SRQ was developed by the World Health Organization (WHO) to screen for a range of mental health disorders.

Findings

• 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.
• Investigators found low-strength evidence that sertraline and CBT provide benefit for depressive symptoms.
  • There is low-strength evidence that CBT is more effective than psychotherapy or placebo for depressive symptoms and quality of life.
  • There is low-strength evidence that acupressure is more effective for reducing depression than sham acupressure or usual care.
  • There is moderate-strength evidence that high-dose vitamin D3 is ineffective.
• A single small multisite study examined the PHQ-9 (³10) compared to the gold standard SCID for MDD. Sensitivity and specificity were both 0.92, and AUC was 0.94. No studies examined the PHQ-2.

Five pharmacological trials reported adverse events (AEs). Sertraline (antidepressant) trials most commonly reported AEs. Some harm outcomes were more common with Sertraline than placebo including study dropouts due to AEs, nausea, and other non-serious AEs, but none of these were more severe than for the general population. There also were some dropouts due to AEs in the trial of high-dose Vitamin D3. There were no serious AEs in the non-pharmacological trials.

Implications for VA

Review findings will be used to help guide the selection and implementation of depression screening for Veterans with ESRD, and the interventions for those with comorbid depressive disorders. Currently in VA settings, Veterans with ESRD are screened for depression using a variety of tools, including the PHQ-9. These findings highlight the moderate positive predictive values in this population. Clinicians should be prepared to validate positive screens prior to making treatment decisions that may be burdensome or introduce the possibility of harm.

Research Gaps/Future Research

Diagnostic accuracy studies of depression tools conducted in US and Veteran ESRD populations are needed. Given that the PHQ-9 is a commonly used tool in VA and community settings, additional research evaluating its performance characteristics is warranted. There are a handful of studies supporting the use of the BDI-II as a screening tool for MDD in this population. Larger studies with representative samples evaluating a range of thresholds would help guide decision-making and implementation.

No studies examined the impact of screening on outcomes, and only one study examined subgroup differences; also important, but missing, is evidence of potential demographic and clinical differences. Future research also is needed to better evaluate interventions for depression in this population.

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.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/esrd-depression.cfm (Intranet only, copy and paste the URL into your browser if you have intranet access.)

ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR&D's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers –; and to disseminate these reports throughout VA.

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