Review Article

The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic Review

Pavan Chopra,1 Chelsea K. Ayers,2 Jennifer R. Antick,3,4 Devan Kansagara,1,2,5 and Karli Kondo 2,6

Abstract Adults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment–related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. 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 is more effective than (undefined) psychotherapy and placebo for de- pression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed.

Systematic Review registry name and registration number: PROSPERO, CRD42020140227 KIDNEY360 2: 558–585, 2021. doi: https://doi.org/10.34067/KID.0003142020

Introduction treatment nonadherence, along with decreased quality The incidence and prevalence of ESKD in the United of life (QoL) and sleep (8–13). States have increased steadily over the past four dec- There are no established guidelines for treating de- ades (1). Psychiatric and mental-health disorders are pression in adults with ESKD. Less than 25% of those more common in adults with ESKD, and include issues on dialysis who are diagnosed with moderate or severe such as depression, dementia, delirium, substance depression actually undergo treatment (12,14,15). abuse, psychoses, anxiety, and personality disorders There are few studies of treatment efficacy in this (2–4). Adults with ESKD experience major depressive population and, while some studies include only par- disorder at anywhere from three to over six times ticipants with clinical depression, others include any that of the general US population, depending on the adults with ESKD. Psychosocial treatments and cog- method of assessment, and depression is the most nitive behavioral therapy (CBT) are commonly used; common mental-health issue in this population (5,6). however, interventions vary widely, the evidence is The effect of depression can be extremely detrimen- limited, and findings may vary on the basis of the tal for a wide range of patient outcomes for those with presence and severity of depression. ESKD. For instance, adults with ESKD who have de- Given the wide variation in depression treatment pressive symptoms have a 12% higher rate of hospi- options for adults with ESKD, it is vital to understand talization than those without (7), and those with ESKD the depression treatment–related outcomes for those in and psychiatric issues have a 40%–50% increased risk this population suffering from clinical depression. The of all-cause mortality (8). Comorbid depression is as- purpose of this review is to better understand the sociated with increased emergency-department visits, benefits and harms of treatment for depression in these hospitalizations, hospital length of stay, suicide, and adults.

1Department of Medicine, Oregon Health and Science University, Portland, Oregon 2Evidence Synthesis Program, Veterans Affairs Portland Health Care System, Portland, Oregon 3School of Graduate Psychology, Pacific University, Hillsboro, Oregon 4Legacy Good Samaritan Medical Center, Portland, Oregon 5Center to Improve Veteran Involvement in Care, Veterans Affairs Portland Health Care System, Portland, Oregon 6Research Integrity Office, Oregon Health and Science University, Portland, Oregon

Correspondence: Dr. Karli Kondo, Veterans Affairs Portland Health Care System, Mail Code R&D 71, 3710 SW US Veterans Hospital Road, Portland, OR 97239-2999. Email: [email protected]

558 Copyright © 2021 by the American Society of Nephrology www.kidney360.org Vol 2 March, 2021 KIDNEY360 2: 558–585, March, 2021 Depression Treatment for Adults with ESKD, Chopra et al. 559

8,050 Citations identified from electronic database searches*: 4,872 from PubMed/Ovid MEDLINE June 24, 2020 2,466 from EMBASE June 24, 2020 330 from PsycINFO June 24, 2020 271 from Ovid EBM Reviews (CDSR, DARE, HTA, Cochrane CENTRAL)June 24, 2020 86 from ClinicalTrials.gov June 24, 2020 25 from WHO ICTRP June 24, 2020 0 from VA HSR&D June 24, 2020

3 Citations identified from reference lists of relevant articles and reviews, key experts, and other sources

8,053 Citations compiled for review of titles and abstracts

7,861 Titles and abstracts excluded for lack of relevance

192 Potentially relevant articles for full text review 163 Excluded publications: 9 Articles unavailable 4 No English language publication 78 Excluded population 41 Excluded study design or publication type 15 No comparator of interest 16 Diagnostic accuracy studies included in parent VA review (not intervention studies) 29 Total included studies

Observational RCTs: studies 26 (harms only): 3

Legend: *after deduplication

Figure 1. | The flow diagram of the literature-review process shows 26 RCTs and 3 observational studies. *After deduplication. CDSR, Cochrane Database of Systematic Reviews; DARE, Database of Abstracts of Reviews of Effects; EBM, Evidence-Based Medicine; HSR&D, Health Services Research and Development Service; HTA, Health Technology Assessment; RCTs, randomized controlled trials; VA, Veterans Affairs; WHO ICTRP, World Health Organization International Clinical Trials Registry Platform.

Materials and Methods of systematic reviews and other relevant articles, and con- Topic Development tacted experts to identify additional studies. To identify This systematic review was part of a larger review com- unpublished literature, we searched the VHA Health Serv- missioned by the Veterans Health Administration (VHA) ices Research and Development website, ClinicalTrials.gov, (16). A protocol describing the review plan was posted to and the World Health Organization International Clinical PROSPERO, a systematic review registry, before study ini- Trials Registry Platform. Search strategies were developed tiation (CRD42020140227). Our methods and reporting fol- in consultation with a research librarian and peer reviewed low Preferred Reporting Items for Systematic Reviews and by another research librarian using the instrument for Peer Meta-Analyses guidelines (17). See Supplemental Table 1 for Review of Search Strategies (see Supplemental Appendix the scope and parameters of the systematic review. 1) (18).

Data Sources and Searches Study Selection To identify trials examining the treatment of depression in Studies were eligible if they (1) included adults with adults with ESKD, we searched Ovid MEDLINE, PsycINFO, dialysis-dependent ESKD not slated for transplant and de- Elsevier EMBASE, and the Ovid Evidence-Based Medicine pression, defined by established thresholds for chronically Reviews (Cochrane Database of Systematic Reviews, Data- ill populations (19–23); (2) directly compared any pharma- base of Abstracts of Reviews of Effects, Health Technology cologic or nonpharmacologic treatments for depression to Assessment, Cochrane CENTRAL, etc.) from database in- placebo, wait-list control, or other intervention; (3) were ception through June 2020. We reviewed the bibliographies randomized controlled trials (RCTs) or nonrandomized 6 KIDNEY360 560

Table 1. Characteristics of randomized controlled trials of interventions for depression and studies examining harms of depression treatment in adults with ESKD

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Pharmacologic Blumenfield et al. (30); Fluoxetine versus 2 sites; hospital dialysis NR Cutoff for inclusion: HAM-D; BDI-II; NR N514; Yr NR placebo centers; New York, NY HAM-D score $16 MADRS; BSI; VAS Other inclusion criteria: age 18–70, normal liver function Friedli et al. (33); Sertraline versus Multisite (5); renal units; 12% Female; age (SD), Cutoff for inclusion: BDI-II; MINI; MADRS MADRS: 24.5 (4.5) N530; April placebo England 61.7 (13.2) yr; race, 67% BDI-II score $16, versus 25.3 (4.2) 2013–May 2015a White, 13% Black, 13% MINI mild to Asian, 7% mixed moderate MDD, MADRS score $18 Other inclusion criteria: excluded if already on SSRIs (56) Gharekhani et al. (35); V-3 Fatty acid versus 2 sites; HD centers; HD duration (SD), 70.7 Cutoff for inclusion: BDI-II 23.52 (7.49) versus 21 N554; Yr NR placebo Tehran, Iran (45.1) mo, 4 h, 2–33 per BDI-II score $16 (4.72); median (IQR): 22 wk; 48% female; age Other inclusion criteria: (17–28) versus 21 (SD), 56.8 (13.09) yr adults, HD $3mo (16.50–22.75) and all had same HD Rx Haghighat et al. (36); Synbiotic supplement 1 site; hospital HD 52% Female; age (SD), Cutoff for inclusion: $8 HADS 9.16 (1.11) versus 9.77 N549; Yr NR versus probiotic; center; Iran 46.64 (10.69) yr Other inclusion criteria: (1.77) versus 9.20 (1.30); supplement versus stable patient on HD P50.63 placebo with arteriovenous fistula, age 30–65, HD 33 per wk for $3mo Hosseini et al. (38); Citalopram versus Single site; hospital HD 55% Female; age (SD), Cutoff for inclusion: HADS 9.42 (3.11) versus 9.58 N544; Yr NR psychologic training center; Iran 52.3 (15.6) yr HADS $8 (3.47) Other inclusion criteria: NA Mehrotra et al. (44); Sertraline versus CBT Multisite (3 states); 41 Median time on dialysis, Cutoff for inclusion: BDI-II; MINI; QIDS- QIDS-C mean (range): N5120; 2017 dialysis facilities; United 31 mo; mean HD session BDI-II $15, then SR; QIDS-C SERT 10.9 (9.6–12.1) States, NM, TX, WA length (SD), 3.9 (0.4) h; confirmed by MINI versus CBT 12.2 history of major (11.0–13.5) depression, 42%; 43% Other inclusion criteria: BDI-II mean (range): female; age (SD), 51 (13) age $21, ESKD, on SERT 25.8 (23.3–28.4) yr; race/ethnicity, 43% HD for $3mo versus CBT 26.2 White, 28% Black, 28% (23.6–28.8) Hispanic, 8% Native American, 12% other; education, 40% #high school INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 1. (Continued)

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Taraz et al. (46); Sertraline versus Single site; outpatient HD for 4 h 33 per wk, Cutoff for inclusion: BDI-II 29 (13) versus 23 (11); N550; placebo HD clinic; Tehran, Iran 43%; time on HD, 42 mo; BDI-II $16 P50.24 Yr NR 59% female; age (SD), 60 Other inclusion criteria: (22) yr; all others NR age 18–80, HD $3mo using arteriovenous fistula Wang et al. (49); Radix Bupleuri herbal Single site; Dalian, HD duration (SD), 26 Cutoff for inclusion: NR MADRS 23.9 (7.8) versus 24.6 N5160; 2013 supplement versus Northeast China (13) versus 29 (15) mo; Other inclusion criteria: (7.4) placebo 75% female; education, aged 30–55 yr; no approximately 86% ,9 history of repeated yr; concurrent suicidal behavior, antidepressant severe substance medication use, 51% abuse, severe versus 46% depression impairing verbal abilities, family history of depression, or brain injury/ disease Wang et al.(50); Vitamin D3 versus 3 sites; dialysis centers, 39% Female; age, 54% Cutoff for inclusion: BDI-II 22.7 (4.3) versus 21.9 N5746; Yr NR placebo HD and PD, outpatient; 18–64 yr; 46% $65 yr; BDI-II $16 (5.4); P50.31 Southeast China other demographics, NR Other inclusion criteria: ESKD, current conventional maintenance PD

(three exchanges per 561 al. et Chopra ESKD, with Adults for Treatment Depression day) or HD (33 per wk, 4–4.5 h per session) for $3 mo, age $18 yr, 15–30 ng/ ml plasma 25(OH)D Nonpharmacologic Al Saraireh et al. (27); CBT versus PSE Multisite; 5 hospital Dialysis duration, NR; Cutoff for inclusion: NR HAM-D PSE 19.6 (5.4) versus N5130; 2017 dialysis units; Jordan approximately 50% Other inclusion criteria: CBT 19.5 (5.4); no 52 female; age (SD), 52 diagnosis of chronic difference, t (103) 0.13; (10.7) yr; education, 71% kidney failure, P50.89 #high school; chronic dialysis $1 yr, employment, 82% verbal unemployed; race/ comprehension/ insurance, NR communication 6 KIDNEY360 562 Table 1. (Continued)

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Babamohamadi et al. Quran versus TAU Single site; hospital 43% Female; age (SD), Cutoff for inclusion: BDI-II 33.6 (6.7) versus 29.3 (28); N560; Yr NR dialysis ward; Iran 53.3 (11.4) yr; race, NR; BDI-II score $20 (9.0); mean difference, education, 75% less than Other inclusion criteria: -4.3 (95% CI, 28.7 to diploma; employment, age 18–65, command 0.0); P50.05 NR (56% “poor”); of Arabic, HD for $6 insurance, NR mo, hemodynamically stable Beizaee et al. (29); Guided imagery versus Single site; HD center; 41% Female; age (SD), Cutoff for inclusion: NR HADS 10.82 (2.70) versus 11.55 N580; 2015–2016 TAU Iran 47.21 (8.34) yr; Other inclusion criteria: (2.29) education, 46% HD 33 per wk for $6 secondary school; mo, age 35–65 yr, employment, 25% read/write in Farsi, unemployed intact cognitive functions on the basis of AMT Cukor et al. (31); CBT versus wait list 2 sites; dialysis units; 73% Female; age, NR; Cutoff for inclusion: SCID-I; BDI-II; HAM- SCID-I with major N565; Yr NR Brooklyn, NY race, 94% Black; BDI-II score $10 D depression: 55% versus education (SD), 11.2 42% (3.4) yr; employment, Other inclusion criteria: BDI-II: 25.3 (9.3) versus 83% unemployed; ESKD with HD for $6 21.4 (8.9) insurance, NR mo HAM-D: 15.0 (6.2) versus 13.5 (5.0) Duarte et al. (32); CBT versus 2 sites; dialysis units; HD, 33 per wk for 4 h Cutoff for inclusion: BDI-II; MINI BDI-II: 24.2 (9.7) versus N590; Yr NR psychotherapy Brazil average; 63% female; MDD with MINI 27.3 (10.7); P50.15 age (SD), 52.4 (15.9) yr; Other inclusion criteria: MINI: 6.4 (1.3) versus 6.4 race, 78% White; ESKD with HD for $3 (1.2); P50.96 education, 83% mo #primary school; employment/insurance, NR Frih et al. (34); N541; Exercise (endurance- Single site; hospital; HD, 4 h 33/wk; HD Cutoff for inclusion: NR HADS Approximately 12 2012–2013a resistance training) Tunisia duration, 72.7 (12.7) mo; Other inclusion criteria: versus approximately 13 versus TAU age (SD), 64.2 (3.4) yr; excluded chronic lung (exact scores NR) 0% female; other disease, ischemic demographics, NR heart disease, uncontrolled arrhythmias or hypertension, hemodynamically unstable, or musculoskeletal disorders, those regularly exercising INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 1. (Continued)

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Heshmatifar et al. (37); Benson relaxation Single site; hospital HD HD, 33 per wk; 18% Cutoff for inclusion: NR BDI-II 32.46 (9.86) versus 30.58 N570; 2013 technique versus TAU unit; Iran female; age, 9% 18–35, Other inclusion criteria: (9.24) 33% 35–45, 45% 45–55, aged 18–65 yr, HD 33 15% 55–65 yr; race, NR; per wk for $6mo, education, 94% #high regular patient of the school; employment, center 42% unemployed; insurance, NR Kargar Jahromi et al. Telenursing versus TAU Single site; hospital HD T versus C:56% versus Cutoff for inclusion: NR DASS-21 16.60 (1.50) versus 16.72 (55); N560; 2014 unit; Iran 40% female; education, Other inclusion criteria: (1.83); P50.40 4% .high school; aged 18–65 yr; HD unemployed, 60% 3–4h33 per wk for versus 44%; other $6mo;no demographics, NR transplants, hospitalizations, or antidepressant Rx Kalani et al. (39); Acupressure versus 3 sites; HD centers; Iran 44% female; age (SD), Cutoff for inclusion: BDI-II T 27.5 (9.1) versus sham N596; 2011 sham versus TAU 53.4 (13.9); race, NR; BDI-II score $10 25.7 (7.7) versus C 24.6 education, 31% Other inclusion criteria: (8.6) nonliterate; ESKD diagnosis, age employment, 50% $18, HD for $3 mo, unemployed, 41% mental and retired; insurance, NR psychologic ability to participate

Kouidi et al. (40); Exercise training versus Single site; hospital HD, 33 per wk for 4 h; Cutoff for inclusion: NR BDI-II; HADS BDI-II: 22.29 (6.71) 563 al. et Chopra ESKD, with Adults for Treatment Depression N550; Yr NR sedentary control renal unit; Greece 42% female; age (SD), versus 22.30 (6.81) 46.3 (11.2) yr; education, Other inclusion criteria: HADS: 10.63 (2.60) 10.2 (3.4) yr; ESKD, 4 h HD 33 per versus 10.40 (2.50) employment, 17% wk for $6mo unemployed; race/ insurance, NR Lerma et al. (41); CBT versus waiting list 2 sites; HD units; Mexico HD, 33 per wk for 3–4 Cutoff for inclusion: BDI-II 13.6 (7.6) versus 15.8 N560; Yr NR City, Mexico h; 52% female; age (SD), BDI-II score of 10–29 (10.0) 41.8 (14.7) yr; education, points 36% elementary; Other inclusion criteria: employment, 26% ESKD, literate, no unemployed; race/ psychiatric illness, insurance, NR regular attendance of HD sessions 3–4hHD 33 per wk for $6mo Li et al. (42); N572; Home nursing visits Single site; hospital; Dialysis duration (SD), Cutoff for inclusion: NR Zung SDS 63.34 (6.28) versus 64.27 2018–2019 versus telephone Hainan, China 22.68 (10.25) mo; 44% Other inclusion criteria: (6.11); P50.53 follow-up female; age (SD), 55.8 age 30–80, on home (6.2) yr; education, 56% PD $3 mo, kidney #middle school failure 6 KIDNEY360 564 Table 1. (Continued)

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Liao et al. (43); N5128; Comprehensive nursing Single site; hospital; HD duration (SD), 43.56 Cutoff for inclusion: NR Zung SDS 60.83 (22.67) versus 2017 versus conventional Hainan, China (13.95) mo; 44% female; Other inclusion criteria: 64.02 (28.58); P50.49 care age (SD), 52.87 (10.46) age $18, on HD $3 yr; education, 57% mo for CRF/ESKD ,high school Rahimipour et al. (45); Hope therapy versus Multisite; hospitals; Iran HD, 2–33 per wk for 4 Cutoff for inclusion: NR DASS-21 13.36 (3) versus 13.64 N550; Yr NR control h; 48% female; age (SD), Other inclusion criteria: (3.5); P50.76 47.82 (15.12) yr; race/ aged 18–65 yr; HD education/ 2–33 per wk for $3 employment/insurance, mo; not taken NR medication for depression, anxiety, or stress Thomas et al. (47); MBSR versus TAU Single site; hospital HD 33% Female; age (SD), Cutoff for inclusion: PHQ-9 12.7 (4.2) versus 11.9 N541; 2016 unit; Montreal, Canada 65 (13) yr; race, 49% PHQ-9 score $ 6 and/ (5.8) White, 51% non-White; or GAD-7 score $6 education, 63% # high Other inclusion criteria: school; employment/ on maintenance HD, insurance, NR spoke English or French Tsay et al. (48); Acupressure versus 4 sites; hospital dialysis Duration HD (SD), 50.06 Cutoff for inclusion: BDI-II Acupressure 20.37 N5108; Yr NR TEAS versus control centers; Northern (44.15) mo; 66% female; BDI-II score $10 (10.65) versus TEAS Taiwan age (SD), 58.16 (12.19) Other inclusion criteria: 18.20 (11.11) versus C yr; employment, 76% ESKD diagnosis, age 21.61 (11.69) retired or unemployed; $18, HD for $3 mo, race/education, NR fatigue, PSQI score $5 Widyaningrum and Latihan Pasrah Diri Single site; hospital HD HD 23 per wk; 61% Cutoff for inclusion: BDI-II 23 (5.34) versus 23.39 Djarwoto (51); versus control unit; Java, Indonesia female; age (SD), 50.06 BDI-II $16 (5.02) N536; 2012 (7.39) yr; education, 78% Other inclusion criteria: # high school; aged 18–60 yr, CKD insurance, 6% adults on 23 per wk uninsured; HD for $3mo employment/race, NR INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 1. (Continued)

Author (Reference); N Clinical Characteristics/ Baseline Depression Intervention/ N Sites; Study Setting; Depression Screening Randomized; Years of Demographics of Study Inclusion Criteria Score, Mean (SD), T Comparator Country/US Region Tool(s) Enrollment Population versus C

Harms-only studies Assimon et al. (57); SSRIs with higher QT- US Renal Data System 53% Female; age (SD), Inclusion: new SSRI NA NA N565,654; prolonging potentialb Database 67.0 (17.2) yr; race, 36% users who received 2007–2014 versus SSRIs with Black; ethnicity, 19% HD during the 180 d lower QT-prolonging Hispanic before SSRI initiation potentialc and had continuous Medicare Part A, B, and D coverage. Excluded: ,18 yr at start of baseline, dialysis vintage #90 d at the start of baseline, presence of an implantable automatic cardiac defibrillator, receipt of hospice care during the baseline period, and missing demographic data Guirguis et al. (56); SSRI observational Multisite; NR; England 37% Female; age (SD), ASSertID study BDI-II, PHQ-9 BDI-II: 26 N541; 2013–2015a 62 (16) yr; race, 27% non- participants who PHQ-9: 12 White were excluded from the RCT (33) phase

because they were 565 al. et Chopra ESKD, with Adults for Treatment Depression already on SSRIs Vangala et al. (58); SSRI versus no SSRI US Renal Data System Patients versus controls: Inclusion: Medicare Part NA NA N554,032; Database female, 58% versus 52%; D, receipt of a low- 2009–2015 age (SD), 71 (12) versus income subsidy, RRT 61 (14) yr; 29% versus start date, 49% Black; 22% versus demographic data, 19% Hispanic; 39% a Medical Evidence versus 25% non- Report from 1995 or Hispanic White later, .90 d HD

T, treatment group; C, control group; NR, not reported; NY, New York; HAM-D, Hamilton Depression Rating Scale; BDI-II, Beck Depression Inventory-II; MADRS, Montgomery–Åsberg Depression Rating Scale; BSI, Brief Symptom Inventory; VAS, Visual Analogue Scale; MINI, Mini International Neuropsychiatric Interview; MDD, major depressive disorder; SSRIs, selective serotonin reuptake inhibitors; HD, hemodialysis; Rx, prescription; IQR, interquartile range; HADS, Hospital Anxiety and Depression Scale; NA, not available; CBT, cognitive behavioral therapy; NM, New Mexico; TX, Texas; WA, Washington; QIDS-SR, Quick Inventory of Depressive Symptomatology–Self-Report; QIDS-C, QIDS-Clinician; SERT, sertraline; PD, peritoneal dialysis; 25(OH)D, 25-hydroxyvitamin D; PSE, psychoeducation; TAU, treatment as usual; AMT, Abbreviated Mental Test; SCID-I, Structured Clinical Interview for Diagnostic and Statistical Manual-IV Axis I Disorders; DASS-21, 21-Item Depression, Anxiety, and Stress Scale; SDS, Self-Rating Depression Scale; CRF, chronic renal failure; MBSR, mindfulness-based stress reduction; PHQ-9, Patient Health Questionnaire-9; GAD, Generalized Anxiety Disorder; TEAS, transcutaneous electrical acupoint stimulation; PSQI, Pittsburgh Sleep Quality Index; ASSertID, A Study of Sertraline in Dialysis; RCT, randomized controlled trial. aPart of the larger ASSertID study. bCitalopram and escitalopram. cFluoxetine, fluvoxamine, paroxetine, and sertraline. 566 KIDNEY360

controlled trials in any setting (for harms outcomes, we also RCTs (one 8-week, poor-quality trial of fluoxetine [N514] included observational studies); (4) assessed patient out- [30], and one recent, fair-quality, 6-month trial of sertraline comes of interest (e.g., depression symptom severity, sui- [A Study of Sertraline in Dialysis; ASSertID; N530] [33]) cidal ideation, QoL); and (5) were published in English. We found no difference in depressive-symptom reduction between excluded studies examining adults with AKI or those with those assigned to SSRIs or placebo. One fair-quality, 12- CKD stages 1–4. See Supplemental Appendix 2 and Sup- week, Iranian RCT (N550) (46) found that participants who plemental Table 1 for complete selection criteria. All studies received sertraline reported a significant reduction in depressive were reviewed for inclusion by two independent reviewers symptoms compared with placebo. Small sample sizes and at the title/abstract and full-text levels. Discords were re- differences in depression assessment tools and statistical solved through consensus or consultation with a third analyses detracted from the quality of these studies (see reviewer. Table 4 for quality ratings). SSRIs versus Active Comparators.SSRIs versus CBT A 5 Data Abstraction and Quality Assessment recent, fair-quality, multisite, head-to-head RCT (N 120) in From included studies, we abstracted details on study the United States (A Trial of Sertraline versus Cognitive design, sample size, setting, population characteristics, par- Behavioral Therapy for ESKD Adults with Depression; ticipant selection criteria, and intervention details (including ASCEND [44]) provides low-strength evidence that the dosage, timing, and administration methods; dura- sertraline and CBT are similar when used for the reduction tion of treatment and follow-up; outcomes; and relevant of depressive symptoms (Tables 3 and 4). Over the 12-week harms). Data from studies meeting inclusion criteria were study period, both groups improved significantly. Participants abstracted by one reviewer and confirmed by an addi- who received sertraline experienced significantly greater tional reviewer. improvement (effect estimate, 21.85; 95% CI, 23.55 to 20.16; Two reviewers independently assessed the methodologic Table 2) when assessed by a clinician (Quick Inventory of quality of each study using criteria established by the US Depressive Symptomatology). There was no difference Preventive Services Taskforce and adapted for depression between groups in self-reported symptoms (i.e., Beck interventions (24–26). Disagreements were resolved by con- Depression Inventory-II; effect estimate, 22.9; 95% CI, 26.7 sensus or a third reviewer. to 0.8; Table 2).SSRIs versus Psychologic Training A small (N544), 3-month, poor-quality RCT (38), con- ducted in Iran, provides insufficient evidence for the com- Data Synthesis and Analysis “ ” We qualitatively synthesized the evidence for each treat- parison of citalopram to psychologic training in partic- ment category and outcome of interest. We were unable to ipants with ESKD and depression (Tables 3 and 4). quantitatively synthesize the evidence because there were Although both arms reported a reduction in depressive too few studies examining the same intervention and report- symptoms, there was no difference between groups ing the same outcome measure (52). (Table 2). Harms of SSRIs. Adverse events (AEs) reported in the Using an established method by Berkman et al. (53), for included trials of SSRIs in adults with depression and ESKD each intervention, we assessed the overall strength of evi- dence (SOE) that considers study limitations, directness, were similar in type and frequency to those reported by the consistency, precision, and reporting bias to classify the general population on SSRIs (59). One trial reported a higher SOE for each outcome independently as high, moderate, rate of dropout due to AEs associated with sertraline (33% 5 low, or insufficient; we used separate guidance for the versus 0%; P 0.04) (33). Across all four trials (30,33,44,46), applicability (external validity) of the evidence to the clinical a wide range of AEs (e.g., nausea, headaches, dizziness) question (54). Supplemental Table 2 describes SOE domains were reported by participants in both treatment and control and grading in more detail. groups, but they were not consistently nor uniformly repor- ted (Table 5). Additionally, three observational studies focused spe- Results cifically on potential harms related to SSRIs in adults with We reviewed 8050 titles and abstracts, 192 of which ESKD and depression (Table 6). Two examined Medicare qualified for full-text review. Of those, we included a total beneficiaries who received SSRIs that were included in of 26 RCTs; nine examined pharmacologic interventions and the US Renal Data System registry. A case-control study 17 examined nonpharmacologic interventions for the treat- (N554,032) found that SSRIs increased the risk of hip ment of depression in adults with ESKD. We also included fracture regardless of dose or duration (58), and the three observational studies reporting harms of selective second (57), a retrospective cohort study (N565,654), serotonin reuptake inhibitors (SSRIs; see Figure 1 for liter- found that adults, especially older adults and women, ature flow, and Table 1 for study characteristics). taking SSRIs with higher QT-prolonging potential (i.e., citalopram and escitalopram) were at higher risk for Pharmacologic Treatments sudden cardiac death (adjusted hazard ratio, 1.18; 95% fi SSRIs CI, 1.05 to 1.31). The nal study was a follow-up to the SSRIs versus Placebo. Three studies comparing SSRIs ASSertID RCT (33) that examined SSRI practice patterns with placebo report conflicting findings and provide insuf- in adults with ESKD, and included participants who were ficient evidence to draw conclusions about their effective- already on SSRIs at baseline (N541). Findings suggest ness in treating depression in adults with ESKD (see Table 2 poor medication management and both under- and over- for study results and Table 3 for SOE ratings). Two small US treatment (56). INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360

Table 2. Efficacy of interventions from randomized controlled trials for depression in adults with ESKD

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Pharmacologic SSRIs versus control Blumenfield et al. (30); 1997; 7 Fluoxetine: 20 mg/d for 8 wk Matched placebo Mean change from baseline (at 4 NA Poor versus 7; Tx58 wk, F/U58 wk; at 8 wk): wk BDI-II: 212 versus 24.17 (P50.05); 29.57 versus 28.8 (P50.91) BSI: 26.29 versus 0.2 (P50.04); 24.43 versus 23.2 (P50.88) HAM-D: no 4 wk assessment; 29.00 versus 27.5 (P50.72) MADRS: 27.20 versus 26.75 (P50.93); 211.14 versus 26.67 (P50.45) VAS: 2210.0 versus 258.3 (P50.37); 2303.0 versus 2140 (P50.45) Electronic VAS: 2262.4 versus 5.6 (P);50.05 2389.0 versus 287.8 (P50.13) Friedli et al. (33); 2017; 15 Sertraline: 100 mg/d (50 mg/d to Matched placebo MADRS between-group NA Fair versus 15; Tx56 mo, F/U56 start; dose could be increased difference at 6 mo: 20.67 (95% moa to maximum at 2 and 4 mo) CI, 25.7 to 4.4) Within-groups decrease 567 al. et Chopra ESKD, with Adults for Treatment Depression significant for both groups Mean change at study end: MADRS: 214.5 (95% CI, 220.2 to 28.8) versus 214.9 (95% CI, 218.4 to 211.5) BDI-II: 215.7 (95% CI, 224.3 to 27.1) versus 213.0 (95% CI, 19.6 to 26.4) Taraz et al. (46); 2013; 25 Sertraline: 100 mg/d (50 mg/ Matched placebo BDI-II scores (SD) for baseline, 6 NA Fair versus 25; Tx512 wk, F/U512 d for first 2 wk) wk, 12 wk, D baseline to 12 wk: wk sertraline, 29 (13), 21 (11.5), 15 (5.5), 211.3 (5.8) versus placebo, 23 (11), 22.5 (8.5), 22.5 (9), 20.5 (5); comparison D baseline to 12 wk between groups, P50.001 6 KIDNEY360 568 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

SSRIs versus active comparator Hosseini et al. (38); 2012; 22 Citalopram: 20 mg/d Psychologic training: six 1-h Postintervention HADS (SD): NA Poor versus 22; Tx53 mo, F/U53 sessions on kidney-disease 6.26 (4.18) (P50.001) versus mo education, problem solving, 7.33 (4.80) after training stress management, and (P50.04); no difference muscle-relaxation techniques between groups (P50.16) Between-groups mean differences also NS (P50.65) Mehrotra et al. (44); 2019; 60 Sertraline: 200 mg/d unless CBT: ten 60-min sessions during QIDS-C scores (SD): 5.9 (4.5) NA Fair versus 60; Tx512 wk, limited by AEs (titration began HD for 12 wk, adapted for versus 8.1 (5.1) F/U512 wk at 25 mg/d and adjusted each maintenance HD population Effect estimate: 21.85 (95% CI, visit) 23.55 to 20.16) BDI-II scores: 14.1 (95% CI, 11.2 to 17.0) versus 18.7 (95% CI, 15.2 to 22.2) Effect estimate: 22.9 (95% CI, 26.7 to 0.8) Supplements versus placebo Gharekhani et al. (35); 2014; 27 V-3 Fatty acids: 1800 mg/d for 4 Matched placebo: paraffin oil Mean end of study BDI-II (SD): NA Poor versus 27; Tx54 mo, F/U54 mo capsules 13.44 (5.66) versus 20.33 (7.56) mo Difference (SD): 210.08 (8.07) versus 20.88 (8.41); P50.001 Within groups: Significant decrease (P,0.001) versus no significant change Haghighat et al. (36); 2019; 16 Synbiotic supplement: L. Matched placebo End-of-treatment HADS-D NA Good versus 18 versus 15; Tx512 acidophilus strain T16, B. scores (SD): synbiotic 6.92 wk, F/U512 wk bifidum strain BIA-6, B. lactis (1.27) versus placebo 9.40 (1.5); strain BIA-7, B. longum strain P,0.001; BIA-8 (2.73107 CFU/g each) Synbiotic (SD) 6.92 (1.27) versus per 5 g sachet 1 prebiotic (5 g probiotic 8.48 (1.61); P50.011 FOS 1 5 g GOS 1 5 g inulin per Mean difference in HADS-D three 5 g sachets); probiotic scores from baseline: supplement same as above, symbiotic, 22.24 (95% CI, except prebiotics replaced with 23.29 to 21.38); probiotic, placebo 21.28 (95% CI, 22.05 to 20.53); placebo, 0.20 (95% CI, 20.43 to0.76); P50.001 Synbiotic versus placebo (post hoc): P,0.001 INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Wang et al. (49); 2015; 80 Radix Bupleuri herbal Placebo Mean (SD) MADRS scores at 3 QoL (RAND-36): change from Poor versus 80; Tx and F/U53 supplement: 1 g root powder mo: 13.32 (8.25) versus 16.73 baseline 14.21 versus 21.12; mo in capsule daily (9.46) MD, 24.61 (95% CI, 211.32 Change from baseline MADRS: and 2.75); P50.04 211.36 versus 22.24; Mean difference, 4.72 (95% CI, 0.69 to 9.12); P50.02 Wang et al. (50); 2019; 373 High-dose oral vitamin D3: 52- Matched placebo No between-groups difference in NA Fair versus 373; Tx and F/U552 wk treatment of 50,000 IU/wk D values wk Within-group BDI-II scores (SD), baseline to end of study: 22.7 (4.3) to 19.6 (3.7) (P50.02) versus 21.9 (5.4) to 20.8 (5.1) (P50.03) Nonpharmacologic Cognitive behavioral therapy Al Saraireh et al. (27); 2018; 65 CBT: seven individual 1-h PSE: 7 individual 1-h sessions Post-test HAM-D scores (SD): NA Poor versus 65; Tx512 wk, sessions following the 15.0 (5.5) versus 11.1 (2.3) F/U512 wk traditional CBT sessions Between-groups depression protocol scores favored PSE (t54.68; P,0.01) over CBT Cukor et al. (31) (crossover); CBT: individual 60-min CBT Wait-list control BDI-II: mean change score (SD) QoL: treatment effect, 112.0 (SD, Fair 2014; 38 versus 27; Tx53 chairside during dialysis; during treatment:211.7 (1.5) 3.4; P50.003) points versus

mo, F/U56mo modifi ed for population; 10 points (P,0.001) versus 24.8 111.3 points (SD, 3.7; P50.01) 569 al. et Chopra ESKD, with Adults for Treatment Depression sessions over 3 mo (1.4) points (P,0.001) Raw mean (SD) change: 24.7 (9.8) Raw mean (SD) score change: to 11.7 (9.8) versus 14.5 (8.5) to 99.5 (27.9) to 115.3 (25.5) versus 9.1 (6.5) 110.6 (25.1) to 119.7 (24.7); Mean (SD) change in BDI-II score P50.04 in untreated group during wait-list period: 26.7 (1.7) points; P,0.001 (raw mean change, 21.9 [8.9] to 14.5 [8.5]). Magnitude of improvement Fluid adherence: model- greater in the intervention-first estimated mean change score group versus wait-list (SD) during treatment 21.3% condition (P50.03) (0.3) Dkg/d (P50.001) versus 21.1% (0.3) Dkg/d (P50.001) HAM-D: the difference in mean Raw mean (SD) change: 4.0 (2.0) change score between treated to 2.8 (1.6) versus 3.6 (2.0) to 2.5 and untreated groups was (2.0); P50.002 highly significant (P,0.001) SCID-I: between groups not reported 7 KIDNEY360 570 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Duarte et al. (32); 2009; 46 CBT: group CBT sessions, 90 min Individualized psychotherapy BDI-II: after 3 mo, 14.1 (SD, 8.7) Suicide Risk Module (MINI): Fair versus 44; Tx512 wk, 13 per wk for 12 wk, followed (routinely available in dialysis versus 21.2 (SD, 9.1); P50.001; baseline 2.2 (SD, 5.1) versus 1.4 F/U59mo by 6 mo maintenance with unit) 30–50 min 13 per wk for after 9 mo, 10.8 (SD, 8.8) versus (SD, 3.5); P50.23; after 3 mo, monthly meetings 12 wk; followed by as-needed 17.6 (SD, 11.2); P50.002 1.2 (SD, 4.2) versus 0.7 (SD, psychologic care for 6 mo 1.9); P50.43; after 9 mo, 0.6 (SD, 1.2) versus 0.6 (SD, 2.0); P50.95 MINI: the mean change from Overall reduction, within-group baseline (SE) favored comparison: significant intervention reduction within T group (P50.007) versus C (P50.13) After 3 mo: 4.5 (SE, 0.4) versus 2.1 QoL: CBT group significantly (SE, 0.6); P,0.001 improved several dimensions After 9 mo: 4.4 (SE, 0.4) versus 2.9 of KDQOL. Between-groups (SE, 0.5); P50.03 significant improvement in burden of kidney disease, quality of social interaction, sleep, overall health, and mental component summary dimensions Lerma et al. (41); 2017; 38 CBT: 5 group sessions (2 h), 13 Waiting list End-of-treatment BDI-II, 10.2 Overall QoL (PLC): baseline, 99.4 Fair versus 22; Tx55 wk, F/U59 per wk after HD session (SD, 8.2) versus 15.0 (SD, 10.9); (SD, 21.3) versus 91.5 (SD, wk P50.08 19.5); P50.20 Follow-up BDI-II: 7.1 (SD, 7.2) After 5 wk, 109.6 (SD, 21.1) versus 14.7 (SD, 9.7); P50.003 versus 94.0 (SD, 21.0); P50.02 Within-group reduction in After 9 wk, 112.5 (SD, 23.8) scores: P,0.001 versus P50.87 versus 91.3 (SD, 22.5); P50.004 RR of reducing depressive Overall within-group P50.001 symptoms (between groups), versus P50.663; Cohen d50.93 1.7 (large) Adjusted RR between groups for depression, 0.33 (95% CI, 0.05 to 0.55; 33% clinical utility) Nursing interventions Kargar Jahromi et al. (55); Telenursing: 30-min telephone TAU DASS-21 depression subscale NA Poor 2016; 30 versus 30; follow-up sessions 30 d after after intervention (mean [SD]): Tx5unclear, F/U530 d dialysis shift 8.96 (1.17) versus 16.20 (1.60); P50.05 Li et al. (42); 2020; 36 versus Home nursing visits: care, Telephone follow-up at 1, 3, and After intervention SDS: 36.48 QoL (KDQOL-36): both groups Poor 36; Tx56 mo, F/U56mo guidance for patient and 6 mo after discharge (SD, 5.06) versus 48.80 (SD, experienced significant family, counseling, and dietary 5.27); P,0.001 improvement (P,0.001); guidance Both groups experienced scores in Tx group higher than significant decline in scores C(P,0.001) (P,0.001) INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Liao et al. (43); 2020; 64 versus Comprehensive nursing: health Conventional care After intervention SDS: 51.02 QoL (KDQOL-36) at 3-mo f/u: Poor 64; Tx5unclear, during education 1–23 per wk; CBT; (SD, 20.59) versus 60.06 (SD, greater improvements from inpatient stay, F/U53mo progressive relaxation, 28.91); P50.05 baseline for physical activity, extended f/u care Improvement in scores from mental state, burden of kidney baseline: 9.81 (SD, 19.32) disease, symptoms of kidney versus 3.96 (SD, 10.79); P50.04 disease, and effects of kidney disease in T compared with C (all P,0.05) Acupressure Kalani et al. (39); 2019; 32 Acupressure: applied during first Sham: same as acupressure Post-test BDI-II: T 20.6 versus NA Fair versus 32 versus 32; Tx54wk, 2 h of HD; 33 per wk for 4 wk; group except pressure applied sham 25.5 versus C 24.9; F/U54wk each session lasted 20 min 1 cm from acupressure significant difference T versus pointsControl: TAU sham and C (P50.001 for both); no difference between sham and C (P50.22) Tsay et al. (48); 2014; 36 versus Acupressure: applied for 15 min Control group (not described) Acupressure and TEAS are Fatigue (PFS): baseline T 5.92 Poor 36 versus 36; Tx54wk, 33 per wk for 4 wkTEAS: similarly effective, and (SD, 1.39) versus TEAS 5.60 F/U54wk applied for 15 min 33 per wk significantly more effective (SD, 1.30) versus C 6.01 (SD, for 4 wk than no intervention (P50.009 1.60); follow-up T 4.61 (SD, and P50.008, respectively); no 1.72) versus TEAS 4.70 (SD, difference between 1.50) versus C 5.70 (SD, 1.80); acupressure and TEAS post-hoc analysis found (P50.95) significantly lower levels in T

(P50.006) and TEAS (P50.02) 571 al. et Chopra ESKD, with Adults for Treatment Depression versus C. No difference between T and TEAS Sleep quality (PSQI): baseline T 8.85 (SD, 4.50) versus TEAS 7.12 (SD, 4.51) versus C 9.35 (SD, 3.48); follow-up T 7.80 (SD, 4.00) versus TEAS 6.32 (SD, 4.55) versus C 9.75 (SD, 4.65); compared with controls, significantly better with T (P50.05) and TEAS (P50.016); no difference between T and TEAS 7 KIDNEY360 572 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Exercise Frih et al. (34); 2017; 28 versus Exercise (endurance-resistance) Sedentary controls; no Favors exercise: T HADS SF-36 PCS: T significantly Poor 22; Tx54 mo, F/U54mo training: 60 min, 43 per wk on intervention depression scores were not improved (P,0.01) from nondialysis days different than C before baseline; no difference for C; intervention, but significantly no difference between groups lower than C after intervention at either time point (P,0.01). Within-group decrease also significant for T, but not C Significant group 3 period SF-36 MCS: T improved interaction effect for HADS significantly, but not C; no depression scores: F(1, difference before, but T 5 , fi 39) 43.91, P 0.001 signi cantly better than C after (P,0.01) Kouidi et al. (40); 2010; 25 ET program (intradialytic): Sedentary control Favors ET in both BDI-II and Heart rate variability indices: Poor versus 25; Tx51 yr, F/U51yr warm-up, cycling, HADS scores (P,0.001) Standard deviation of all RR strengthening, cooldown, 33 intervals, mean square per wk, 60–90 min during first successive differences, 2 h of HD session percentage of RR intervals differing by more than 50 ms from the preceding RR,low freqency (LF), high frequency (HF), and LF/HF all significantly increased in exercise group, but not controls; after intervention exercise group was significantly better in all variables, P,0.001 Other interventions Babamohamadi et al. (28); Quran: listen to audio of Quran TAU Post-test BDI-II scores: 14.5 (SD, NA Poor 2017; 30 versus 30; Tx51 recitation on headphones for 4.8) versus 31.6 (SD, 9.2); mo, F/U51mo 20 min, beginning 5 min before P,0.001 dialysis Significant between-subjects treatment effect, independent of age (F59.3, P50.004, Cohen d50.85). INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360 Table 2. (Continued)

Author (Reference); Year; N Findings, Treatment versus Comparator Randomized (T versus C); Treatment Comparator Quality Duration of Treatment and Depression Other outcomes Follow-Up

Beizaee et al. (29); 2018; 40 Guided imagery: 33 per wk for 4 TAU, nearly silent environment Post-test HADS scores: 10.02 (SD, SBP: mean (SD) before, 129.22 Fair versus 40; Tx54 wk, F/U54 wk, in-person with 2.58) versus 11.65 (SD, 2.33) (12.70) versus 132.85 (13.22); wk psychologist; 30 mins before mean (SD) after, 121.75 (12.73) HD session; includes audio versus 134.87 (12.68) recording of nature sounds DBP: mean (SD) before, 82.50 (11.32) versus 81.75 (8.51); mean (SD) after, 81.00 (10.32) versus 81.87 (8.14) HR (SD): before, 77.95 (6.97) versus 75.42 (8.56); after, 73.75 (6.25) versus 77.22 (7.92) Heshmatifar et al. (37); 2015; Benson relaxation technique: TAU Only T group scores decreased; NA Poor 35 versus 34; Tx51 mo, performed 20 min 23 per d for the difference between groups F/U51mo 1mo was significant (P50.01) Rahimipour et al. (45); 2015; Hope therapy: sessions using Control: listening session in Immediately after 8-wk NA Poor 25 versus 25; Tx58 wk, Schneider hope therapy which patients could talk intervention (t512.75; F/U512 wk theory, 13 per wk for 8 wk, about their disease and P,0.001), and at 1-mo follow- 1–1.5 h during first 2 h of problems, 13 per wk for 8 wk up (t513.83; P,0.001) dialysis Thomas et al. (47); 2017; 21 MBSRa: guided, chairside TAUa Change in PHQ-9: 23.0 (SD, 3.9) NA Fair versus 20; Tx 58 wk, F/U58 meditative practices, 10–15 versus 2.0 (SD, 4.7); P50.45 wk min, 33 per wk during hemodialysis sessions

Widyaningrum and Djarwoto LPD relaxation technique and Control group (not described) Significantly decreased BDI-II QoL (KDQOL-SF36): Poor 573 al. et Chopra ESKD, with Adults for Treatment Depression (51); 2013; 18 versus 18; repetitive prayer practice, 23 scores within both groups, and significantly greater change in Tx53 wk, F/U53wk per d for 21 d greater in LPD, but between sleep and overall health group difference NS (P50.20) associated with LPD versus control; no other differences were significant

T, treatment group; C, control group; SSRIs, selective serotonin reuptake inhibitors; Tx, treatment; F/U, follow-up; BDI-II, Beck Depression Inventory-II; BSI, Brief Symptom Inventory; HAM-D, Hamilton Depression Rating Scale; MADRS, Montgomery–Åsberg Depression Rating Scale; VAS, Visual Analogue Scale; NA, not applicable; D, change; HADS, Hospital Anxiety and Depression Scale; AE, adverse event; CBT, cognitive behavioral therapy; HD, hemodialysis; QIDS-C, Quick Inventory of Depressive Symptomatology–Clinician; L. acidophilus, Lactobacillus acidophilus; B. bifidum, Bifidobacterium bifidum; FOS, fructo-oligosaccharides; GOS, galacto-oligosaccharides; HADS-D, Hospital Anxiety and Depression Scale–Depression; QoL, quality of life; PSE, psychoeducation; MINI, Mini International Neuropsychiatric Interview; KDQOL, Kidney Disease Quality of Life; RR, relative risk; PLC, Profile of Quality of Life in the Chronically Ill; DASS-21, 21-Item Depression, Anxiety, and Stress Scale; SDS, Self-Rating Depression Scale; SE.standard error; TEAS, transcutaneous electrical acupoint stimulation; PFS, Piper Fatigue Scale; PSQI, Pittsburgh Sleep Quality Index; SF-36, 36-Item Short Form Health Survey; PCS, Physical Component Scale; MCS, Mental Component Scale; ET, exercise training; MSSD, mean squared successive difference; SBP, systolic BP; DBP, diastolic BP; HR, heart rate; MBSR, mindfulness-based stress reduction; PHQ-9, Patient Health Questionnaire-9; LPD, Latihan Pasrah Diri. aBoth treatment and control groups also received psychoeducational literature on anxiety and depression. 574 KIDNEY360

Table 3. Summary of the evidence on interventions for depression in adults with ESKD

Strength of Evidence Outcome Conclusion (Justification)a

Pharmacologic SSRIs versus controls (k53, n594) Depression severity Fluoxetine (30) Insufficient (NC, SLM) No benefit(k51, n514) Sertraline (33,46) Mixed findings (k52; n580) SSRIs versus active comparator (k52; n5164) Depression severity Sertraline versus CBT (44) Low (SLM, UC) Benefit for both; no difference between groups (k51, n5120) Citalopram versus psychologic training Insufficient (SLH, UC) (38) Benefit for both; no difference between groups (k51, n544) Supplements versus placebo (k54; n5986) Depression severity V-3 Fatty acids (35) Insufficient (NP, SLH, UC) Increased benefit(k51, n554) High-dose vitamin D3 (50) Moderate (SLM, UC) No benefit(k51, n5746) Synbiotic or probiotic (36) Insufficient (UC) Increased benefit(k51, n549) Radix Bupleuri (49)b Insufficient (UC, SLH) Increased benefit(k51, n5137) QoL Radix Bupleuri (49)b Insufficient (UC, SLH) Increased benefit(k51, n5137) Nonpharmacologic CBT versus active comparator (k52; n5220) Depression severity CBT versus psychoeducation (27) Insufficient (SLH, UC) Benefit for both, but favored psychoeducation (k51, n5130) CBT versus psychotherapy (32) Low (SLM, UC) Benefit for both, but favored CBT (k51, n590) Suicide risk CBT versus psychotherapy (32) Low (SLM, UC) Benefit in intervention but not control group; no difference between groups (k51, n590) QoL CBT versus psychotherapy (32) Low (SLM, UC) Increased benefit for some domains of KDQOL (k51, n590) CBT versus control (k52; n5125) Depression severity Increased benefit(k52; n5125) (31,41) Low (SLM) QoL Increased benefit(k52; n5125) (31,41) Low (SLM) Fluid adherence Increased benefit(k51; n 565) (31) Insufficient (SLM, UC) Acupressure versus control (k52; n5204) Depression severityc Acupressure versus TAU (39,48) Low (SLM) Increased benefit(k52; n5204) Acupressure versus sham (39) Increased benefit(k51; n596) Fatigue Acupressure versus TAU (48) Insufficient (SLH, UC) Increased benefit(k51, n5108) Sleep quality Acupressure versus TAU (48) Insufficient (SLH, UC) Increased benefit(k51, n5108) Acupressure versus active comparator (k51, n5108) (48) Depression severity Acupressure versus TEAS Insufficient (SLH, UC) Benefit for both; no difference between groups Fatigue Acupressure versus TEAS Insufficient (SLH, UC) Benefit for both; no difference between groups Sleep quality Acupressure versus TEAS Insufficient (SLH, UC) Benefit for both; no difference between groups Nursing interventions: intensive versus less-intensive nursing (k53; n5260) Depression severity Increased benefit(k53; n5260) Insufficient (SLH, NP) (42,43,55) QoL Increased benefit(k52; n5200) (42,43) Insufficient (SLH, NP) Benson relaxation technique versus control (k51; n570) (37) Depression severity Increased benefit Insufficient (SLH, UC) KIDNEY360 2: 558–585, March, 2021 Depression Treatment for Adults with ESKD, Chopra et al. 575

Table 3. (Continued)

Strength of Evidence Outcome Conclusion (Justification)a

Exercise training versus control (k52 n5100) Depression severity Increased benefit(k52; n5100) (34,40) Insufficient (SLH, UP) HRV Increased benefit(k51; n550) (40) Insufficient (SLH, UC, UP) Guided imagery versus TAU (k51; n580) (29) Depression severity Unclear effect Insufficient (SLM, UC) Vital signs Unclear effect Insufficient (SLM, UC) Hope therapy versus active control (k51; n550) (45) Depression severity Increased benefit Insufficient (SLH, UC, UP) LPD versus control (k51; n536) (51) Depression severity No benefit Insufficient (SLH, UP, UC) QoL No benefit Insufficient (SLH, UP, UC) MBSR versus TAU (k51; n541) (47) Depression severity No benefits Insufficient (SLM, UP, UC) Quran versus TAU (k51; n560) (28) Depression severity Increased benefit Insufficient (SLH, UC, UP)

SSRIs, selective serotonin reuptake inhibitors; k, number of studies; n, sample size; NC, not consistent; SLM, study limitations medium; CBT, cognitive behavioral therapy; UC, unknown consistency; SLH, study limitations high; NP, not precise; QoL, quality of life; KDQOL, Kidney Disease Quality of Life; TAU, treatment as usual; TEAS, transcutaneous electrical acupoint stimulation; UP, unclear precision; HRV, heartrate variability; LPD, Latihan Pasrah Diri; MBSR, mindfulness-based stress reduction. aThe overall strength of evidence for each outcome is determined on the basis of the consistency, coherence, and applicability of the body of evidence, and the internal validity of individual studies. The strength of evidence is classified as follows (53): high, further research is very unlikely to change our confidence on the estimate of effect; moderate, further research is likely to have an important effect on our confidence in the estimate of effect and may change the estimate; low, further research is very likely to have an important effect on our confidence in the estimate of effect and is likely to change the estimate; and insufficient, any estimate of effect is very uncertain. bSome participants were concurrently using antidepressant medications. cSome participants are represented more than once.

Supplements versus Placebo (HADS-D) scores of eight or higher (Tables 3 and 4). High-dose Vitamin D3. A large (N5746), fair-quality, 52- HADS-D scores at the end of treatment were significantly week RCT (50) provides moderate-strength evidence that long- lower in adults receiving synbiotics than those receiving term, high-dose vitamin D3 does not reduce depression placebo (P,0.001) and probiotics (P50.01). HADS-D scores severity in adults with ESKD (Tables 3 and 4). In addition, were also significantly reduced from baseline in the no differences were reported by age, sex, body mass index, or symbiotic compared with placebo (P,0.001) groups, but plasma albumin level. Although overall differences in not in the other comparisons (Table 2). The reported AEs depressive-symptom reduction between groups were were few and mild (Table 5). NS, a subgroup of participants with vascular depression Radix Bupleuri Herbal Supplement. A poor-quality, 3- (but not those with major depressive disorder) receiving month RCT (N5160) (49) of Radix Bupleuri root powder vitamin D3 did report significantly greater reduction in supplements compared with placebo provides insufficient depressive symptoms at 1 year (Table 2). evidence for its use for depression in adults with ESKD Harms of Vitamin D3. AEs associated with high-dose (Tables 3 and 4). Participants who were being treated with vitamin D3, including joint pain, diarrhea, nausea, and antidepressant medications (about half of each group) vomiting, resulted in study withdrawal of five participants. continued on those treatments concurrently during this No statistical analyses of AEs or withdrawals due to AEs were trial. Participants taking Radix Bupleuri experienced significantly reported (50). more reduction in Montgomery–Åsberg Depression Rating Scale V-3 Fatty Acids. A single, poor-quality RCT (N554) scores compared with the placebo group (P50.02; Table 2). They (35),conductedinIran,providesinsufficient evidence also experienced improvement in QoL (measured by RAND-36) to form conclusions about the effect of V-3 fatty acids compared with the placebo group (P50.04). The trial did not versus placebo on depression severity in adults with report on AEs. ESKD (Tables 3 and 4). At 16 weeks, the V-3 fatty acids group reported a significantly greater reduction in depressive symptoms compared with both placebo and Nonpharmacologic Treatments their own baseline. No differences were identified by age, CBT sex, baseline depression severity, or length of time on CBT versus Psychotherapy. One fair-quality RCT (N590) hemodialysis (Table 2). No serious AEs (SAEs) were (32) provides low-strength evidence that small-group CBT reported in this trial. is more effective than brief, individualized psychotherapy Synbiotic and Probiotic Supplements. One good-quality, for reducing depression severity in participants with 12-week RCT (N549) (36) provides insufficient evidence ESKD (Tables 3 and 4). Depressive symptoms improved for the use of synbiotic or probiotic supplements versus significantly in both groups. Participants receiving CBT also placebo on depression severity in Iranian adults with ESKD experienced a significant within-group decrease in suicide and Hospital Anxiety and Depression Scale–Depression risk and improved on several QoL domains (i.e., burden of 7 KIDNEY360 576

Table 4. Quality and applicability assessment of randomized controlled trials

Rating Criteriaa Overall Quality Author (Reference) Funding source Applicability Rating 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Al Saraireh et al. Y NR N NA Y U U N Y N Y N Y U Y NA N Investigator Poor Fair (27) Babamohamadi NR NR N U Y U U N Y N U N Y Y U U N NR Poor Poor et al. (28) Beizaee et al. (29) Y Y Y Y Y Y Y N Y N Y N N U Y NA Y University Fair Fair Blumenfield et al. NR Y U U N U Y Y Y N N N Y U Y N N Industry grant Poor Fair (30) Cukor et al. (31) NR NR Y U YYYYYNNY YUY N NNIDDK Fair Fair Duarte et al. (32) Y Y N U YYYYYNNYYYY N NGovernment Fair Fair Friedli et al. (33) Y Y Y N YYYYYYNNYUY N NNIHgrant Fair Good Frih et al. (34) Y NR U Y Y Y N N Y Y N Y Y U Y N N NR Poor Fair Gharekhani et al. Y U Y N Y N N Y Y Y N N Y Y Y N N University Poor Good (35) Haghighat et al. (36) Y Y Y U YYYYYUYNY Y Y Y NAhvaz Jundishapur Univ Good Fair Med Sci Heshmatifar et al. NR NR Y U Y U U N Y N N Y Y U U N U NR Poor Fair (37) Hosseini et al. (38) U NR Y Y Y U U N Y N N Y Y U Y N N Government Poor Fair Jahromi et al. NR NR Y Y Y Y N Y Y N U N Y Y N U N NR Poor Fair Kalani et al. (39) N U Y U Y U U U Y U Y N Y Y Y U N University Poor Fair Kouidi et al. (40) NR NR Y U Y U U N Y N N Y Y U Y N N NR Poor Fair Lerma et al. (41) Y NR Y U Y Y Y N Y N N N Y Y Y N N Government Fair Fair Li et al. (42) Y N Y Y Y N N N N U U N Y U Y U N NR Poor Fair Liao et al. (43) Y NR Y Y Y U U U Y N N N Y U Y N N NR Poor Fair Mehrotra et al. (44) Y Y U Y Y Y N N Y N Y N Y Y Y Y N Government, University, Fair Fair NIDDK, DCI Rahimipour et al. U NR U U Y U U U N U U U Y U Y U N NR Poor Fair (45) Taraz et al. (46) Y U Y Y Y U U Y Y N N N Y Y Y N N University grant Fair Good Thomas et al. (47) Y NR N U Y Y U N Y N Y N Y Y Y N N University grant Fair Fair Tsay et al. (48) NR NR Y U Y U U N Y N N Y Y U Y N N Government Poor Fair Wang et al. (49) NR NR Y N Y U U Y Y Y Y N Y U Y N N NR Poor Fair Wang et al. (50) Y Y Y Y Y U Y Y Y N N U Y Y Y N N NR Fair Poor Widyaningrum NR NR Y U Y U U U N U U U Y U Y U N NR Poor Poor et al. (51)

Y, yes; NR, not reported; N, no; NA, not applicable; U, unclear; NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases; NIH, National Institutes of Health; Univ Med Sci, University of Medical Sciences; DCI, Dialysis Clinic Inc. aThe quality rating criteria (adapted from the US Preventive Services Task Force criteria [26]) involved evaluating the following questions:(1) randomization adequate?(2) allocation concealment adequate?(3) groups similar at baseline?(4) maintain comparable groups?(5) eligibility criteria specified?(6) outcome assessors masked?(7) care provider masked?(8) patient masked?(9) reporting of attrition, crossovers, adherence, and contamination?(10) important differential loss to follow-up or overall high loss to follow-up?(11) intention-to-treat analysis?(12) postrandomization exclusions?(13) were outcomes prespecified and defined, and ascertained using accurate methods?(14) intervention fidelity?(15) follow-up long enough for outcomes to occur? (minimum 4 wk for drugs)(16) appropriate handling of missing data?(17) evidence of selective outcome reporting? INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360

Table 5. Adverse events reported in depression treatment trials in patients with ESKD

Blumenfield et al. Friedli et al. (33)a Haghighat et al. (36) Mehrotra et al. (44) Taraz et al. (46)b (30) Severity System Adverse Event FLU PBO SERT PBO Probiotic PBO CBT SERT SERT PBO (N56) (N57) (N515) (N515) (N525) (N525) (N560) (N560) (N521) (N522)

Nonserious Autonomic Dry mouth 0 1 ———————— Cardiovascular Cardiac unspecified ——————39—— Hypotension 4 1 ———————— Palpitations —— 10a —————— Gastrointestinal Abdominal pain 1 2 ———————— Constipation 0 1 ———————— Diarrhea 1 1 ———————— Dyspepsia 1 0 ——————64 Gastroenteritis 0 2 ———————— Gastrointestinal ——————11 22 —— unspecified Nausea 5 2 1 0a ————73 Vomiting 3 3 ———————— Musculoskeletal Myalgia 1 1 ———————— Neurologic Dizziness 1 0 1 0a ————53 Headache 3 0 1 0a 11—— 42 Insomnia 2 1 1 0a —————— Nervous system ——————08—— unspecified Sensation disturbance 1 0 ———————— Tremors 1 0 ———————— Psychiatric Abnormal thought 1 0 ———————— Anorexia ————————24 577 al. et Chopra ESKD, with Adults for Treatment Depression Anxiety 0 1 ———————— Nervousness 1 1 ———————— Respiratory Bronchitis 1 0 ———————— Cough 0 2 ———————— Dyspnea 1 0 —— — 1 —— —— Pharyngitis 1 0 ———————— Rhinitis 1 0 ———————— Upper respiratory tract 10———————— infection Skin Furunculosis 1 0 ———————— Pruritus 1 0 ———————— Skin ulcer 0 1 ———————— Sweating —— 10a —————— Other Dehydration 0 1 ———————— Edema 0 1 ———————— Fatigue —— — — — 1 —— —— Flu syndrome 1 0 ———————— Hair loss ————————11 Other unspecified ——————317—— Sexual dysfunction ————————21 Tooth infection 1 0 ———————— 7 KIDNEY360 578 Table 5. (Continued)

Blumenfield et al. Friedli et al. (33)a Haghighat et al. (36) Mehrotra et al. (44) Taraz et al. (46)b (30) Severity System Adverse Event FLU PBO SERT PBO Probiotic PBO CBT SERT SERT PBO (N56) (N57) (N515) (N515) (N525) (N525) (N560) (N560) (N521) (N522)

Severe Gastrointestinal Gastrointestinal ——————11—— unspecified Cardiovascular Cardiac unspecified ——————44—— Other Death —— 10 ——20—— Major bleeding ——————12—— Other unspecified ——————29——

FLU, fluoxetine; PBO, placebo; SERT, sertraline; CBT, cognitive behavioral therapy. aThe events reported in this table are only those that resulted in study dropout. There were other adverse events reported narratively, but it was not clear from the text in which category or study arm they occurred, so they are not recorded in this table. bIt is unclear whether the events of study dropouts were included in these totals. There was one death in each group and some attrition due to adverse events, but the dropouts were not analyzed in this per-protocol study. INY6 :5855 ac,2021 March, 558–585, 2: KIDNEY360

Table 6. Adverse events reported in observational studies of adults with ESKD and depression

Author (Reference); N; Years; Source Treatment versus Comparator Outcomes of Interest Findings

Assimon et al. (57); N565,654; 2007–2014; SSRIs with higher QT-prolonging potentiala 1-yr sudden cardiac death Compared to SSRIs with lower QT- Medicare Recipients in the US Renal Data versus SSRIs with lower QT-prolonging prolonging potential, those with higher System Database potentialb QT-prolonging potential were associated with higher risk of sudden cardiac death (AHR, 1.18; 95% CI, 1.05 to 1.31); this association was more pronounced among older adults (AHR, 1.19; 95% CI, 1.05 to 1.35), women (AHR, 1.23; 95% CI, 1.06 to 1.44), patients with conduction disorders (AHR, 1.47; 95% CI, 1.05 to 2.06), and those treated with other non-SSRI QT- prolonging medications (AHR, 1.29; 95% CI, 1.10 to 1.50) Guirguis et al. (56); N541; 2013–2015; Antidepressants (no comparator) Antidepressant-management practices At baseline, 30 patients had BDI‐II scores ASSertID Study related to NICE guidelines $16, and 22 remained high at follow‐up; At baseline, 11 patients had BDI‐II scores ,16; five of 11 were $16 on follow‐up; 27 of the 41 patients (66%) either deteriorated 579 al. et Chopra ESKD, with Adults for Treatment Depression or failed to improve; 16 patients (39%) had no review of antidepressant medication; a significant proportion of patients were taking agents cautioned against, or with no available prescribing information in, for patients on HD, or they were taking doses that might be considered subtherapeutic; 15% had no evidence of ever having had MDD over their lifetime according to the MINI, in spite of their being on antidepressants 8 KIDNEY360 580 Table 6. (Continued)

Author (Reference); N; Years; Source Treatment versus Comparator Outcomes of Interest Findings

Vangala et al. (58); N554,032; 2009–2015; SSRI versus no SSRI Hip fracture Any SSRI use was associated with increased Medicare Recipients in the US Renal Data hip fracture risk (AOR, 1.25; 95% CI, 1.17 to System Database 1.35); risk for fracture was estimated for low (AOR, 1.20; 95% CI, 1.08 to 1.32), moderate (AOR, 1.31; 95% CI, 1.18 to 1.43), and high SSRI use (AOR, 1.26; 95% CI, 1.12 to 1.41); the relationship between hip fracture events and SSRI use was also seen in the examination of new short-term use (AOR, 1.43; 95% CI, 1.23 to 1.67); no significant interaction with age, sex, BMI, race, or ethnicity was discovered in the short-term analysis

SSRIs, selective serotonin reuptake inhibitors; AHR, adjusted hazard ratio; ASSertID, A Study of Sertraline in Dialysis; NICE, National Institute for Health and Care Excellence; BDI-II, Beck Depression Inventory-II; HD, hemodialysis; MDD, major depressive disorder; MINI, Mini International Neuropsychiatric Interview; AOR, adjusted odds ratio; BMI, body mass index. aCitalopram and escitalopram. bFluoxetine, fluvoxamine, paroxetine, and sertraline. KIDNEY360 2: 558–585, March, 2021 Depression Treatment for Adults with ESKD, Chopra et al. 581

kidney disease, quality of social interaction, sleep, overall Scale scores were improved from baseline (P,0.001), the health, and mental health) over the study period (Table 2). home-nursing group’sdepressionscoresweresignifi- No study dropouts from serious AEs were reported. cantly lower than the control group after intervention CBT versus Psychoeducation. A poor-quality RCT (27), (P,0.001). Another Chinese study of a comprehensive conducted in Jordan, provides insufficient evidence to form nursing intervention compared with usual care (N5128) conclusions about the comparison of CBT with psychoeducation (43) in adults on hemodialysis found that the intervention (Tables 3 and 4). Participants receiving CBT reported group had significantly greater reduction in Self-Rating asignificantly greater reduction in depressive symptoms Depression Scale scores from baseline (P50.04), and those (both groups reported significant improvement; Table 2). scores were significantly better after intervention com- CBT versus Sertraline. A head-to-head RCT (44) pro- pared with the control group (P50.05). An Iranian RCT vides low-strength evidence that sertraline and CBT are (N560) using the Depression, Anxiety, and Stress Scale similar when used for the reduction of depressive found that telenursing follow-ups compared with usual symptoms in participants with depression and ESKD. care (no telephone follow-ups) resulted in significantly – See the section SSRIs versus CBT above and Tables 2 4 lower depression scores (Table 2) (55). These studies did for more detail. not report on AEs. CBT versus Control. Two fair-quality RCTs (31,41) provide low-strength evidence that CBT is more effective Exercise than wait-list control for reducing depression severity and There was insufficient evidence from two poor-quality improving QoL in participants with ESKD (Tables 3 and 4). studies (34,40) on exercise training for depression in adults There is insufficient evidence to form conclusions about the with ESKD (Tables 3 and 4). One study (N550) (34) exam- benefit of CBT on fluid adherence (31). ined the effect of 4 months of endurance and resistance One study compared outcomes (depressive symptoms, training four times weekly in Tunisian male participants. QoL, and fluid adherence) on the basis of the timing of the Training sessions were on off-dialysis days and the exercise intervention (treatment first or after 90-day wait listing). group significantly improved on HADS-D scores compared Results indicated that participants receiving CBT experi- with sedentary controls. The other, a Greek RCT (N550) enced significantly greater benefit across all outcomes (40), examined intradialytic exercise (during hemodialysis in both phases. However, findings suggest a sequence cycling and strength training) three times per week for effect for depressive-symptom reduction (the treatment- a year and found significant improvement on both the Beck first group experienced greater benefit than the wait- Depression Inventory-II and HADS-D with exercise com- listgroup),butnoneforQoLorfluid compliance pared with sedentary controls (Table 2). AEs were not (Table 2) (31). reported.

Acupressure We found low-strength evidence that acupressure is Other Treatments We included RCTs of six other therapies: Benson relax- more effective than both usual care and sham acupressure ation technique (37), guided imagery (29), hope therapy (45), for reducing depression severity in participants with ESKD Latihan Pasrah Diri (51), mindfulness-based stress reduction (Table 3). There is insufficient evidence to form conclusions (47), and Quran readings for Muslim participants (28). All about the comparison of acupressure to transcutaneous were small, single trials with methodologic challenges, and electrical acupoint stimulation (TEAS) for the reduction of the evidence is insufficient for all interventions (Tables 2–4). depressive-symptom severity, fatigue, or sleep-quality im- Two of these studies (Latihan Pasrah Diri [51] and provement. A fair-quality, three-arm RCT (N596) (39) mindfulness-based stress reduction [47]) reported no AEs, compared acupressure with sham acupressure (i.e., pres- whereas the others did not report on AEs. sure applied 1 cm from the acupressure point) and usual care. Participants receiving acupressure reported a signif- icantly greater reduction in depression symptoms than those receiving sham acupressure or usual care (there Discussion was no difference between sham and usual care). A second In this systematic review, we examined nine RCTs of 5 three-arm RCT (poor quality; N 108) (48) compared acu- pharmacologic interventions and 17 of nonpharmacologic pressure with both TEAS and usual care. Participants in interventions for comorbid depression in adults with ESKD. both the acupressure and the TEAS groups reported We also found three observational studies that contributed greater reductions in depressive symptoms and fatigue, to the evidence on harms of SSRIs. We found moderate- and better-quality sleep than those who received usual care strength evidence that long-term, high-dose vitamin D3 is (Tables 2 and 4). ineffective for reducing depressive symptoms, and low- strength evidence that both sertraline and CBT were similar Intensive Nursing for improving depressive symptoms. We also found low- Three poor-quality RCTs (42,43,55) provide insufficient strength evidence that CBT is more effective than both evidence for the effect of intensive nursing interventions, standard psychotherapy and wait-list controls, and that compared with less-intensive nursing, for improving de- acupressure is more effective than usual care. We found pressive symptoms in adults with ESKD (Tables 3 and 4). insufficient evidence to draw conclusions about all other One study in China (N572) compared home-nursing visits interventions. Overall, we found limited evidence for each with telephone follow-up for adults on peritoneal dialysis intervention, sample sizes were small, and nearly all studies (42). Although both groups’ Zung Self-Rating Depression were hampered by methodologic flaws. 582 KIDNEY360

SSRIs, compared either with placebo or an active com- Another important limitation to the current evidence base parator, were the best-studied pharmacologic interven- is that most of the studies were conducted outside of the tion. No other antidepressant categories were identified. United States and examined participants and health systems Findings from placebo-controlled trials of SSRIs were that differ greatly from the general US population. These mixed, but sertraline at least warrants further study. differences may be reflected in both the patient demograph- Among the three trials examining sertraline, one reported ics and medical disease burden, and in how care is deliv- benefit over placebo, and another found no difference ered, particularly because the majority of US adults on between sertraline and CBT (44). Harms related to SSRIs dialysis receive their care from large dialysis organizations were not uniformly reported. The type and rate of harms in coordination with their nephrology provider. reported and/or evaluated in included RCTs suggest little This is the only systematic review to date that examines to no increase in risk for adults with ESKD compared with both pharmacologic and nonpharmacologic treatment of otherwise healthy adults using SSRIs. Primary side effects depression in adults with ESKD. This review confirms were minor (e.g., nausea, fatigue). However, observational and adds to a 2016 Cochrane review of antidepressants in studies suggest that clinicians should consider known risks adults with ESKD, which included meta-analyses of harms (e.g., QT prolongation) when making prescribing deci- reported in trials included in our report (59). Although we sions, and to coordinate care to avoid over- or under- also included more recent trials, outcomes were not repor- treatment. ted in a way that allowed for a quantitative synthesis of Vitamin D3 is an interesting intervention for adults with harms. Our review adds to the pharmacologic evidence by ESKD, due to the associated risks of hypercalcemia and including studies of dietary supplements. A Cochrane re- hyperphosphatemia (60). Five adults withdrew from the view examining psychosocial interventions for adults with study due to treatment-related AEs. Although not attributed ESKD was recently published (61); however, it includes to hyperphosphatemia, the reported AEs (i.e., joint pain, studies of participants with and without clinical depression. diarrhea, nausea, and vomiting) may be related. The neg- How a participant with ESKD responds to an intervention ative finding regarding vitamin D3, along with its risks, may vary widely depending on the severity of their baseline suggests that clinicians should not recommend its use as depressive symptoms. To reduce clinical heterogeneity, we a depression treatment in this population. Given the large included only studies with participants meeting established size and length of the trial, the SOE for this finding is depression-screening thresholds for chronically ill popula- moderate, and future studies are unlikely to change tions (19–23). Finally, additional trials included in our re- conclusions. view, particularly the ASCEND (44) and ASSertID trials Very few nonpharmacologic studies reported harms; (33,44), add to both the pharmacologic and nonpharmaco- however, most interventions presented minimal risk. Differ- logic evidence. ences by subpopulation (i.e., demographic, clinical) were Future research, particularly in the United States, is also reported in very few studies, and reported differences needed to better evaluate both pharmacologic and nonphar- were insufficient to form conclusions. Future research macologic interventions for this population. In particular, should uniformly report harms and examine these larger replication studies of CBT, acupressure, and SSRIs subgroups. (such as sertraline), and examination of their effects in Many of the studies were hampered by small sample different subgroups of adults with ESKD and depression sizes, posing challenges related to group comparability and (such as severity of depression, duration of ESKD diagnosis, statistical power. The duration of treatment and follow-up peritoneal versus hemodialysis, and presence of comorbid- varied widely across studies, making it more challenging to ities), will help decision makers to implement depression compare results. For instance, between two studies of ser- treatments that are not only evidence based, but are also the traline, one was twice as long as the other (3 versus 6 best fit for their patient population. months). The methods used to screen for and diagnose depression were heterogeneous, as was the implementation of interventions (e.g., timing, doses, comparators, modes of Disclosures All authors have nothing to disclose. delivery). For example, among CBT studies, although all of them met in person, half of the studies used private sessions, and sessions were conducted in groups in the other studies. Funding Session lengths varied and, in one study, CBT was delivered This research was funded by the US Department of Veterans while the participants were receiving hemodialysis. Given Affairs, VHA, Office of Research and Development, Health Services the association with hemodialysis and somatic complaints, Research and Development. hemodynamic changes, and alterations in mental acuity, treatments (particularly psychologic ones) that are admin- istered during hemodialysis may be confronted with these Acknowledgments challenges; although treating adults outside of hemodialysis The authors wish to thank Ms. Robin Paynter (MLIS) for de- sessions has its own challenges, including the increased time veloping the search strategy and running electronic searches. We burden and physical and mental fatigue. Among other also thank the members of our technical expert panel for their psychologic treatments, some were applied in person, expertise. whereas others were practices expected to be followed at The findings and conclusions in this document are those of the home. In addition to these issues, the lack of methodologic authors who are responsible for its contents, the findings and detail reported in many of the studies resulted in poor- conclusions do not necessarily represent the views of the De- quality ratings and uncertainty about study processes. partment of Veterans Affairs or the US Government. KIDNEY360 2: 558–585, March, 2021 Depression Treatment for Adults with ESKD, Chopra et al. 583

Each author contributed important intellectual content during 11. Kurella M, Kimmel PL, Young BS, Chertow GM: Suicide in the manuscript drafting or revision, accepts personal accountability for United States end-stage renal disease program. J Am Soc Nephrol the author’s own contributions, and agrees to ensure that questions 16: 774–781, 2005 https://doi.org/10.1681/ASN.2004070550 12. Watnick S, Kirwin P, Mahnensmith R, Concato J: The prevalence pertaining to the accuracy or integrity of any portion of the work are and treatment of depression among patients starting dialysis. Am appropriately investigated and resolved. J Kidney Dis 41: 105–110, 2003 https://doi.org/10.1053/ ajkd.2003.50029 13. Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz Author Contributions I, Veis JH: Psychosocial factors, behavioral compliance and survival in urban hemodialysis patients. Kidney Int 54: 245–254, J.R. Antick, D. Kansagara, and K. Kondo provided supervision; 1998 https://doi.org/10.1046/j.1523-1755.1998.00989.x C.K. Ayers was responsible for project administration; C.K. Ayers, 14. Sullivan JE, Choi NG, Vazquez CE, Neaves MA: Psychosocial P. Chopra, D. Kansagara, and K. Kondo reviewed and edited the depression interventions for dialysis patients, with attention to manuscript; C.K. Ayers, P. Chopra, and K. Kondo were responsible Latinos: A scoping review. Res Soc Work Pract 29: 910–923, for investigation; C.K. Ayers and K. Kondo were responsible for 2019 https://doi.org/10.1177/1049731518820134 15. Shirazian S, Grant CD, Aina O, Mattana J, Khorassani F, Ricardo data curation and methodology; and all authors conceptualized the AC: Depression in chronic kidney disease and end-stage renal study, were responsible for formal analysis, and wrote the disease: Similarities and differences in diagnosis, epidemiology, original draft. and management. 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58. Vangala C, Niu J, Montez-Rath ME, Yan J, Navaneethan SD, 60. Covic A, Rastogi A: Hyperphosphatemia in patients with ESRD: Assessing Winkelmayer WC: Selective serotonin reuptake inhibitor use and the current evidence linking outcomes with treatment adherence. BMC hip fracture risk among patients on hemodialysis. Am J Kidney Nephrol 14: 153, 2013 https://doi.org/10.1186/1471-2369-14-153 Dis 75: 351–360, 2020 https://doi.org/10.1053/ 61. Natale P, Palmer SC, Ruospo M, Saglimbene VM, Rabindranath j.ajkd.2019.07.015 KS, Strippoli GF: Psychosocial interventions for preventing and 59. Palmer SC, Natale P, Ruospo M, Saglimbene VM, Rabindranath treating depression in dialysis patients. Cochrane Database of KS, Craig JC, Strippoli GF: Antidepressants for treating depression Syst Rev 12: CD004542, 2019 https://doi.org/10.1002/ in adults with end-stage kidney disease treated with dialysis. 14651858.CD004542.pub3 Cochrane Database Syst Rev (5): CD004541, 2016 10.1002/ 14651858.CD004541.pub3 Received: May 19, 2020 Accepted: January 4, 2021 The Effectiveness of Depression Treatment for Patients with End-Stage Kidney Disease: A Systematic Review Supplemental Material

Contents:

Item S1. Search Strategies (Parent VA Review) ...... 2 Item S2. Study Selection Criteria (Parent VA Review) ...... 8 Table S1. PICOTS by Key Question ...... 10 Table S2. Strength of Evidence Domains and Grading ...... 11 References ...... 12

1

Item S1. Search Strategies (Parent VA Review)

Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1946 to June 24, 2020 Date searched: June 24, 2020 # Searches 1 Kidney Failure, Chronic/ 2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab,kf. 3 Renal Dialysis/ or Hemofiltration/ or Hemodiafiltration/ or Hemodialysis, Home/ or Peritoneal Dialysis/ or Peritoneal Dialysis, Continuous Ambulatory/ 4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab,kf. 5 or/1-4 6 Depression/ or Depressive Disorder/ or Depressive Disorder, Major/ or Depressive Disorder, Treatment- Resistant/ 7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab,kf. 8 or/6-7 9 and/5,8 10 Brief Psychiatric Rating Scale/ or Diagnostic Self Evaluation/ or "Diagnostic Techniques and Procedures"/ or Mental Status Schedule/ or Neuropsychological Tests/ or Patient Health Questionnaire/ or Psychiatric Status Rating Scales/ or exp Psychological Tests/ or exp "Surveys and Questionnaires"/ 11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab,kf. 12 exp Behavior Therapy/ or exp Cognitive Behavioral Therapy/ or exp Mental Health Services/ or exp Psychotherapy/ or Psychosocial Support Systems/ or Social Support/ or Motivational Interviewing/ or Patient Participation/ 13 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab,kf. 14 Antidepressive Agents/ or Antidepressive Agents, Second-generation/ or Serotonin Uptake Inhibitors/ or "Serotonin and Noradrenaline Reuptake Inhibitors"/ or Adrenergic Uptake Inhibitors/ or 5-hydroxytryptophan/ or Amisulpride/ or Bupropion/ or Citalopram/ or Fluoxetine/ or Fluvoxamine/ or Maprotiline/ or Mianserin/ or Paroxetine/ or Quipazine/ or Ritanserin/ or Sulpiride/ or Trazodone/ or Tryptophan/ or Venlafaxine Hydrochloride/ or Viloxazine/ 15 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab,kf.

2

16 Antidepressive Agents, Tricyclic/ or Amitriptyline/ or Amoxapine/ or Clomipramine/ or Desipramine/ or Dothiepin/ or Doxepin/ or Imipramine/ or Iprindole/ or Lofepramine/ or Nortriptyline/ or Opipramol/ or Protriptyline/ or Trimipramine/ 17 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab,kf,nm. 18 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab,kf. 19 Exercise Therapy/ or Resistance Training/ 20 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab,kf. 21 Music Therapy/ 22 music therapy.ti,ab,kf. 23 or/10-22 24 and/9,23 25 limit 24 to english language

PsycINFO 1806 to June 2019 Date searched: June 24, 2020 Searches 1 Kidney Diseases/ 2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab. 3 Dialysis/ or Hemodialysis/ 4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab. 5 or/1-4 6 "Depression (Emotion)"/ or Major Depression/ or Reactive Depression/ or Recurrent Depression/ or Treatment Resistant Depression/ 7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 8 or/6-7 9 and/5,8 10 exp Measurement/ or exp Attitude Measures/ or exp "Checklist (Testing)"/ or exp Inventories/ or exp Psychological Assessment/ or exp Questionnaires/ or exp Rating Scales/ or exp Screening/ or exp Screening Tests/ or exp Standardized Tests/ or exp "Stress and Coping Measures"/ or exp Testing/ 11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab. 12 ("Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic 3

Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or PHQ9 or PHQ-9 or PHQ-ADS or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).tm. 13 exp Treatment/ 14 exp Behavior Modification/ or exp Behavior Therapy/ or Biofeedback Training/ or Contingency Management/ or Self-management/ or Anxiety Management/ or Cognitive Therapy/ or Readiness to Change/ or Relaxation Therapy/ or Self-help Techniques/ or Self-monitoring/ or Stress Management/ 15 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab. 16 Antidepressant Drugs/ or Serotonin Norepinephrine Reuptake Inhibitors/ or Serotonin Reuptake Inhibitors/ or Tricyclic Antidepressant Drugs/ or Bupropion/ or Citalopram/ or Fluoxetine/ or Fluvoxamine/ or "Hydroxytryptophan (5-)"/ or MAPROTILINE/ or Mianserin/ or Paroxetine/ or RITANSERIN/ or Sulpiride/ or Trazodone/ or Tryptophan/ or Venlafaxine/ 17 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab. 18 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab. 19 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog* or coping or psychosocial* or psycho-social* or "social support" or "social work*" or stress).ti,ab. 20 exp Exercise/ 21 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab. 22 Music Therapy/ 23 music therapy.ti,ab. 24 or/10-23 25 and/9,24 26 limit 25 to english language

Embase.com Date search: June 24, 2020 # Search #26 #25 AND [embase]/lim NOT ([embase]/lim AND [medline]/lim) #25 #9 AND #23 AND [english]/lim #24 #9 AND #23 #23 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 #22 'music therapy':ti,ab,kw #21 'music therapy'/de #20 (((aerobic OR resistance) NEAR/2 (exercis* OR program* OR therap* OR train*)):ti,ab,kw) OR ((exercise NEAR/2 (program* OR therap* OR train*)):ti,ab,kw) OR 'cross training':ti,ab,kw #19 'kinesiotherapy'/de OR 'resistance training'/de #18 nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmacolog*:ti,ab,kw OR 'non pharmacolog*':ti,ab,kw 4

#17 amitriptyline:ti,ab,kw OR amoxapine:ti,ab,kw OR clomipramine:ti,ab,kw OR desipramine:ti,ab,kw OR dothiepin:ti,ab,kw OR doxepin:ti,ab,kw OR imipramine:ti,ab,kw OR iprindole:ti,ab,kw OR lofepramine:ti,ab,kw OR nortriptyline:ti,ab,kw OR opipramol:ti,ab,kw OR protriptyline:ti,ab,kw OR trimipramine:ti,ab,kw OR gabapentin:ti,ab,kw OR sildenafil:ti,ab,kw OR vardenafil:ti,ab,kw #16 'tricyclic antidepressant agent'/de OR 'amitriptyline'/de OR 'clomipramine'/de OR 'desipramine'/de OR 'dosulepin'/de OR 'doxepin'/de OR 'imipramine'/de OR 'iprindole'/de OR 'lofepramine'/de OR 'nortriptyline'/de OR 'opipramol'/de OR 'protriptyline'/de OR 'trimipramine'/de #15 ((antidepress*:ti,ab,kw OR 'anti depress*':ti,ab,kw OR '5 hydroxytryptophan':ti,ab,kw OR amisulpride:ti,ab,kw OR bupropion:ti,ab,kw OR citalopram:ti,ab,kw OR escitalopram:ti,ab,kw OR fluoxetine:ti,ab,kw OR fluvoxamine:ti,ab,kw OR maprotiline:ti,ab,kw OR mianserin:ti,ab,kw OR paroxetine:ti,ab,kw OR quipazine:ti,ab,kw OR ritanserin:ti,ab,kw OR sulpiride:ti,ab,kw OR trazodone:ti,ab,kw OR tryptophan:ti,ab,kw OR 'venlafaxine hydrochloride':ti,ab,kw OR viloxazine:ti,ab,kw OR ssri:ti,ab,kw OR ssris:ti,ab,kw OR 'selective serotonin reuptake':ti,ab,kw OR 'selective serotonin re-uptake':ti,ab,kw OR snri:ti,ab,kw OR snris:ti,ab,kw OR serotonin:ti,ab,kw) AND 'noradrenaline reuptake inhibitor':ti,ab,kw OR serotonin:ti,ab,kw) AND 'noradrenaline reuptake inhibitors':ti,ab,kw OR nri:ti,ab,kw OR nris:ti,ab,kw OR 'norepinephrine reuptake inhibitor':ti,ab,kw OR 'norepinephrine reuptake inhibitors':ti,ab,kw #14 'antidepressant agent'/de OR 'serotonin uptake inhibitor'/de OR 'serotonin noradrenalin reuptake inhibitor'/de OR 'adrenergic receptor affecting agent'/de OR '5 hydroxytryptophan'/de OR 'amisulpride'/de OR 'amfebutamone'/de OR 'citalopram'/de OR 'fluoxetine'/de OR 'fluvoxamine'/de OR 'maprotiline'/de OR 'mianserin'/de OR 'paroxetine'/de OR 'quipazine'/de OR 'ritanserin'/de OR 'sulpiride'/de OR 'trazodone'/de OR 'tryptophan'/de OR 'venlafaxine'/de OR 'viloxazine'/de #13 'cognitive behavior*':ti,ab,kw OR 'cognitive behaviour*':ti,ab,kw OR intervention:ti,ab,kw OR interventions:ti,ab,kw OR nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmac*:ti,ab,kw OR 'non pharmac*':ti,ab,kw OR pharmac*:ti,ab,kw OR program*:ti,ab,kw OR psych*:ti,ab,kw OR psychosocial:ti,ab,kw OR 'psycho social':ti,ab,kw OR rehabilitation:ti,ab,kw OR therapy:ti,ab,kw OR therapies:ti,ab,kw OR treat*:ti,ab,kw #12 'behavior therapy'/de OR 'cognitive behavioral therapy'/de OR 'mental health service'/de OR 'psychotherapy'/de OR 'psychosocial care'/de OR 'social support'/de OR 'motivational interviewing'/de OR 'patient participation'/de #11 (checklist*:ti,ab,kw OR 'check list*':ti,ab,kw OR questionnaire:ti,ab,kw OR questionnaires:ti,ab,kw OR instrument:ti,ab,kw OR instruments:ti,ab,kw OR inventory:ti,ab,kw OR inventories:ti,ab,kw OR scale:ti,ab,kw OR scales:ti,ab,kw OR schedule:ti,ab,kw OR schedules:ti,ab,kw OR screen:ti,ab,kw OR screened:ti,ab,kw OR screening:ti,ab,kw OR 'beck depression':ti,ab,kw OR bdi:ti,ab,kw OR bdi2:ti,ab,kw OR 'geriatric depression scale':ti,ab,kw OR gds:ti,ab,kw OR 'hamilton rating scale for depression':ti,ab,kw OR 'hospital anxiety':ti,ab,kw) AND 'depression scale':ti,ab,kw OR hads:ti,ab,kw OR 'kidney disease quality of life':ti,ab,kw OR kdqol:ti,ab,kw OR 'medical outcomes study short form health survey 36':ti,ab,kw OR 'mos sf36':ti,ab,kw OR 'minnesota multiphasic personality inventory':ti,ab,kw OR mmpi:ti,ab,kw OR 'multiple affect adjective check list':ti,ab,kw OR maacl:ti,ab,kw OR 'patient health questionnaire':ti,ab,kw OR phq2:ti,ab,kw OR 'phq 2':ti,ab,kw OR phq9:ti,ab,kw OR 'phq 9':ti,ab,kw OR 'prime-md':ti,ab,kw OR 'epidemiologic studies depression scale':ti,ab,kw OR ced:ti,ab,kw OR cesd:ti,ab,kw OR bref:ti,ab,kw OR dass21:ti,ab,kw OR idid:ti,ab,kw OR 'quick inventory of depressive symptomatology self-report':ti,ab,kw OR 'qids sr':ti,ab,kw OR 'rand 36‐item health survey':ti,ab,kw OR 'rand 36':ti,ab,kw OR 'short form 36':ti,ab,kw OR 'sf 36':ti,ab,kw OR 'structured clinical interview':ti,ab,kw OR scid:ti,ab,kw OR 'self-rating depression scale':ti,ab,kw OR sds:ti,ab,kw OR 'short form health survey 36':ti,ab,kw OR sf36:ti,ab,kw #10 'brief psychiatric rating scale'/de OR 'diagnostic procedure'/de OR 'neuropsychological test'/de OR 'patient health questionnaire'/de OR 'psychological rating scale'/de OR 'psychologic test'/de OR 'questionnaire'/de #9 #5 AND #8 #8 #6 OR #7 #7 depressed:ti,ab,kw OR depressive:ti,ab,kw OR depression*:ti,ab,kw OR suicidal:ti,ab,kw OR suicide:ti,ab,kw OR suicides:ti,ab,kw #6 'depression'/exp #5 #1 OR #2 OR #3 OR #4 #4 dialysis:ti,ab,kw OR haemodiafiltration:ti,ab,kw OR hemodiafiltration:ti,ab,kw OR 'haemo diafiltration':ti,ab,kw OR 'hemo diafiltration':ti,ab,kw OR haemofiltration:ti,ab,kw OR hemofiltration:ti,ab,kw OR 'haemo filtration':ti,ab,kw OR 'hemo filtration':ti,ab,kw OR haemodialysis:ti,ab,kw OR hemodialysis:ti,ab,kw OR 'haemo dialysis':ti,ab,kw OR 'hemo dialysis':ti,ab,kw 5

#3 'hemodialysis'/exp OR 'hemofiltration'/exp OR 'hemodiafiltration'/exp OR 'peritoneal dialysis'/exp #2 (((chronic OR endstage OR 'end stage' OR endstate OR 'end state' OR failure OR 'long term' OR maintenance) NEAR/2 (kidney OR renal)):ti,ab,kw) OR eskd:ti,ab,kw OR eskf:ti,ab,kw OR esrd:ti,ab,kw OR esrf:ti,ab,kw #1 'chronic kidney failure'/exp

EBM Reviews: Cochrane Central Register of Controlled Trials June 2020 Cochrane Database of Systematic Reviews 2005 to June 24, 2020 Database of Abstracts of Reviews of Effects 1st Quarter 2016 Health Technology Assessment 4th Quarter 2016 Date searched: June 24, 2020 # Searches 1 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab. 2 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab. 3 or/1-2 4 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 5 and/3-4 6 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab. 7 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab. 8 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab. 9 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab. 10 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab. 11 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab. 12 music therapy.ti,ab. 13 or/6-12 14 and/5,13

6

ClinicalTrials.gov Date searched: June 24, 2020 ( depressed OR depressive OR depression* OR suicidal OR suicide OR suicides ) AND INFLECT EXACT ( "Active, not recruiting" OR "Completed" OR "Suspended" OR "Terminated" OR "Withdrawn" OR "Unknown status" ) [OVERALL-STATUS] AND ( ( chronic OR endstage OR end-stage OR failure ) AND ( kidney OR renal ) OR ESKD OR ESKF OR ESRD OR ESRF OR dialysis OR haemodiafiltration OR hemodiafiltration OR haemo-diafiltration OR hemo-diafiltration OR haemofiltration OR hemofiltration OR haemo-fi ) [DISEASE]

WHO ICTRP Date searched: June 24, 2020 (((chronic OR endstage OR end-stage OR failure) AND (kidney OR renal)) OR ESKD OR ESKF OR ESRD OR ESRF) AND (depress* OR suicid*)

VA HSR&D https://www.hsrd.research.va.gov/research/ Date searched: June 24, 2020 Separately searched terms: kidney and renal. Reviewed result lists

7

Item S2. Study Selection Criteria (Parent VA Review)

Inclusion/Exclusion Criteria for Full Text Review 1. Language: Is the full text of the article in English? Yes...... …...... ……...... …...... Proceed to #2 No ...... ………...... …………….………………Code X1. STOP

2. Population: Does the study include adults with ESRD or CKD (or CKF, CRF) undergoing maintenance dialysis? Yes …………………………………………………….………………………….Proceed to #3 No ……Code X2. Add code B (example: X2 – B) if retaining for background/discussion. STOP

3. Population: Does the study include adults screened, diagnosed with, or treated for depression? Yes………………...... ……………...... …...... Proceed to #4 No… ……………………..Code X2. Add code B if retaining for background/discussion. STOP

4. KQ1: Does the study examine screening tool(s) for depression? Yes………………...... ……………...... …...... Proceed to Q5 No ………………………………………………………...……...Code 0 for KQ1. Proceed to Q6

5. KQ1: Does the study compare a screening tool against the gold standard (e.g., clinical interview – e.g., SCID) or another validated depression assessment tool? Yes, gold standard (e.g., clinician interview/SCID)…Code I for "I or X Code" and 1 for KQ1. STOP Yes, another depression tool…………...Code I for "I or X Code" and 1 - Tool for KQ1. STOP No ………………………………………………………...…Proceed to Q6 (and code 0 for KQ1)

6. Study Design: Is the study original quantitative research, a systematic review (SR) or meta- analysis (MA; exclude other literature reviews, editorials, qualitative research, etc.)? Yes………………...... ……………...... …. If SR or MA code X3 - PEARL. If other quantitative, Proceed to Q7 No…….Code X3. Add code B (example: X3 – B) if retaining for background/discussion. Code 0 for all KQs. STOP

7. Comparator: The study has a comparison group (other screening tool, no screening, other intervention, waitlist controls, etc.). Pre-post studies are excluded. Yes …………………………………………………….…………………………. Proceed to Q8 No...…Code X4. Add code B if retaining for background/discussion. Code 0 for all KQs STOP

8. Outcomes: Does the study report 1 or more of the following outcomes specifically for the population of interest (ESRD/CKD maintenance dialysis) Diagnostic test performance: sensitivity, specificity, positive predictive value, and negative predictive value; Therapeutic impact: timing, setting, or type of treatment.; Intermediate and Patient outcomes: depressive symptoms, mortality, suicide attempts or completion, hospitalization, ED/urgent care utilization, patient satisfaction, adherence to dialysis, medication, or treatment, pain medication reduction, BP/metabolic control, quality of life, other outcomes (e.g., employment); Adverse effects or unintended consequences. Prevalence and correlational studies are excluded. Yes …………………………………………………….……………….……………Proceed to Q9 No.……Code X5. Add code B if retaining for background/discussion. Code 0 for all KQs STOP 8

9. Does the article or main study (from which the data were gathered) examine the impact of screening or the effectiveness of treatment for depression (including subgroup differences or harms)? Yes, screening ……………………………………………………………………..Proceed to Q10 Yes, treatment: Is depression an inclusion criterion, or is the average depression score of participants equivalent to at least moderate depression? (Cutoffs: PHQ-9 ≥ 10;1 CES-D ≥ 18;2 HAM- D ≥ 12;3 BDI-II ≥ 16;2,3 BDI-II ≥ 13;3 HADS ≥ 84,5) No…………………………………………………………………………………Code X2 Yes…………………………………………………………………………Proceed to Q10 No ………………………….Code X5. Add code B if retaining for background/discussion. STOP

10. Harms: Does the article examine the harms of screening or treatment? Yes………………………………….Code I for "I or X Code" and 1 for KQ4. Proceed to Q11. No………………………………………………………………Code 0 for KQ4. Proceed to Q11.

11. Study Design: Does the article describe data collected as part of an RCT or NRCT? Yes…………………………………………………….………………………….Proceed to Q12. No………………………………………………………..Code X3. Code 0 for KQs 2, 3. STOP.

12. KQs 2 and 3: Does the study examine the impact of screening or treatment? Yes………………………………Code I for "I or X Code" and 1 for KQ2 if screening and/or 1 for KQ3 if treatment. Code 0 for KQ 2 or 3 if NA. STOP. No…………………………………………………….…………Code 0 for KQs 2 and 3. STOP. All articles should have at least 1 code. If not, re-review. Be sure that all articles are coded 0 for all KQs that are not relevant.

9

Table S1. PICOTS by Key Question

Key Question: KQ1: What is the effectiveness of depression KQ2: In patients with KQ3: Do the benefits or harms of treatment differ by: treatment in patients with ESRD and ESRD, what are the a. patient characteristics or other social determinants of depression: potential harms of health? a. pharmacological? treatment for depressed b. setting? b. non-pharmacological? patients? c. provider characteristics (e.g., mental health, PCP)? c. pharmacological and non-pharmacological i. pharmacological? d. other (e.g., patient engagement/ receptivity to treatment, treatments combined? ii. non-pharmacological? social support)? e. timing and type of follow up?

Population Adults with ESRD and depression (Cutoffs: PHQ-9 ≥ 10;1 CES-D ≥ 18;2 HAM-D ≥ 12;3 BDI-II ≥ 16;2,3 BDI ≥ 13;3 HADS ≥ 84,5). If study specified inclusion of subclinical or mild depression in eligibility criteria, we excluded it. Intervention Pharmacological (4+ weeks) and non-pharmacological treatments for depression Comparators Placebo, waitlist control, other intervention Outcomes Intermediate and Patient outcomes: depressive Adverse effects or Intermediate and Patient outcomes: depressive symptoms, symptoms, mortality, suicide attempts or unintended consequences mortality, suicide attempts or completion, hospitalization, completion, hospitalization, ED/urgent care ED/urgent care utilization, patient satisfaction, adherence to utilization, patient satisfaction, adherence to dialysis, medication, or treatment, pain medication dialysis, medication, or treatment, pain reduction, BP/metabolic control, quality of life, other medication reduction, BP/metabolic control, outcomes (e.g., employment) quality of life, other outcomes (e.g., employment) Timing Any Settings All settings in U.S. or international (VHA, hospital community, community mental health, ED, urgent care, other community) Study design Systematic reviews, RCTs, NRCTs Systematic reviews, RCTs, NRCTs, Observational studies Note. Subpopulations may include: Patient demographic characteristics or social determinants of health; treated by HD (home or clinic); treated by PD (home or clinic); clinical severity (ESRD or depression); setting (e.g. 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

10

Table S2. Strength of Evidence Domains and Grading

Strength of Evidence Domains Study Limitations Directness Consistency Precision Reporting Bias (Internal Validity) • Direct: the evidence links • Degree to which • Degree of certainty • Publication bias: • Degree to which intervention to a health outcome included studies surrounding an effect nonreporting of the full the include • Indirect: only intermediate find either the estimate with respect study studies for a outcomes are available same direction or to a given outcome • Selective outcome given outcome (e.g., lab tests) when similar magnitude based on the reporting bias: have a high outcomes of interest are of effect sufficiency of sample nonreporting or likelihood of health outcomes (e.g., • Direction of effect: size and number of incomplete reporting of adequate mortality effect sizes have events planned outcomes or protection against • Indirect: data come from proxy the same sign (are • In a meta-analysis, reporting of unplanned bias assessed respondents on the same side of consider whether the outcomes through: • Indirect: data do not come from no effect or a MID) CI crossed a • Selective analysis o Study Design head-to-head comparisons but • Magnitude of threshold for a MID reporting bias: reporting o Study Conduct from two or more bodies of effect: The range of • Consider the of one or more favorable evidence effect sizes is narrowness of analyses for a given similar (may individual study CI outcome while not Indirectness implies that more consider overlap in ranges or reporting other, less than one body of evidence is confidence significance of p- favorable analyses required to link evidence to the intervals) values in evidence most important health outcomes. base Strength of Evidence Grades Low Insufficient Moderate High We have limited confidence that the We have no evidence, we are We are moderately confident We are very confident that the estimate of effect lies close to the true unable to estimate an effect, or that the estimate of effect lies estimate of effect lies close to effect for this outcome. we have no confidence in the close to the true effect for this the true effect for this

estimate of effect for this outcome. outcome. The body of evidence has major or outcome. numerous deficiencies (or both). We The body of evidence has The body of evidence has few believe that additional evidence is No evidence is available, or the some deficiencies. We believe or no deficiencies. We believe needed before concluding either that body of evidence has that the findings are likely to that the findings are stable, the findings are stable or that the unacceptable deficiencies, be stable, but some doubt that is, another study would estimate of effect is close to the true precluding reaching a conclusion. remains. not change the conclusions. effect. Abbreviations: CI = confidence interval; MID = minimum important difference; SOE = strength of evidence Note: This table provides a summary of the elements described in Berkman and colleagues, 20156

11

References

1. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder. 2016;Verson 3.0. 2. CMS Center for Clinical Standards & Quality. Summary of Representative Clinical Depression Screening Tools. November 30, 2015. 3. Furukawa TA, Reijnders M, Kishimoto S, et al. Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking. Epidemiol Psychiatr Sci. 2019:1-13. 4. Stafford L, Berk M, Jackson HJ. Validity of the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 to screen for depression in patients with coronary artery disease. Gen Hosp Psychiatry. 2007;29(5):417-424. 5. Applied Health Sciences (Mental Health). Assessing the validity of the PHQ-9, HADS, BDI-II and QIDS-SR in measuring severity of depression in a UK sample of primary care patients with a diagnosis of depression. University of Aberdeen. 2011. 6. Berkman ND, Lohr KN, Ansari MT, et al. Grading the strength of a body of evidence when assessing health care interventions: an EPC update. J Clin Epidemiol. 2015;68(11):1312-1324.

12

The Effectiveness of Depression Treatment for Patients with End-Stage Kidney Disease: A Systematic Review Supplemental Material

Contents:

Item S1. Search Strategies (Parent VA Review) ...... 2 Item S2. Study Selection Criteria (Parent VA Review) ...... 8 Table S1. PICOTS by Key Question ...... 10 Table S2. Strength of Evidence Domains and Grading ...... 11 References ...... 12

1

Item S1. Search Strategies (Parent VA Review)

Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1946 to June 24, 2020 Date searched: June 24, 2020 # Searches 1 Kidney Failure, Chronic/ 2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab,kf. 3 Renal Dialysis/ or Hemofiltration/ or Hemodiafiltration/ or Hemodialysis, Home/ or Peritoneal Dialysis/ or Peritoneal Dialysis, Continuous Ambulatory/ 4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab,kf. 5 or/1-4 6 Depression/ or Depressive Disorder/ or Depressive Disorder, Major/ or Depressive Disorder, Treatment- Resistant/ 7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab,kf. 8 or/6-7 9 and/5,8 10 Brief Psychiatric Rating Scale/ or Diagnostic Self Evaluation/ or "Diagnostic Techniques and Procedures"/ or Mental Status Schedule/ or Neuropsychological Tests/ or Patient Health Questionnaire/ or Psychiatric Status Rating Scales/ or exp Psychological Tests/ or exp "Surveys and Questionnaires"/ 11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab,kf. 12 exp Behavior Therapy/ or exp Cognitive Behavioral Therapy/ or exp Mental Health Services/ or exp Psychotherapy/ or Psychosocial Support Systems/ or Social Support/ or Motivational Interviewing/ or Patient Participation/ 13 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab,kf. 14 Antidepressive Agents/ or Antidepressive Agents, Second-generation/ or Serotonin Uptake Inhibitors/ or "Serotonin and Noradrenaline Reuptake Inhibitors"/ or Adrenergic Uptake Inhibitors/ or 5-hydroxytryptophan/ or Amisulpride/ or Bupropion/ or Citalopram/ or Fluoxetine/ or Fluvoxamine/ or Maprotiline/ or Mianserin/ or Paroxetine/ or Quipazine/ or Ritanserin/ or Sulpiride/ or Trazodone/ or Tryptophan/ or Venlafaxine Hydrochloride/ or Viloxazine/ 15 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab,kf.

2

16 Antidepressive Agents, Tricyclic/ or Amitriptyline/ or Amoxapine/ or Clomipramine/ or Desipramine/ or Dothiepin/ or Doxepin/ or Imipramine/ or Iprindole/ or Lofepramine/ or Nortriptyline/ or Opipramol/ or Protriptyline/ or Trimipramine/ 17 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab,kf,nm. 18 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab,kf. 19 Exercise Therapy/ or Resistance Training/ 20 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab,kf. 21 Music Therapy/ 22 music therapy.ti,ab,kf. 23 or/10-22 24 and/9,23 25 limit 24 to english language

PsycINFO 1806 to June 2019 Date searched: June 24, 2020 Searches 1 Kidney Diseases/ 2 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab. 3 Dialysis/ or Hemodialysis/ 4 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab. 5 or/1-4 6 "Depression (Emotion)"/ or Major Depression/ or Reactive Depression/ or Recurrent Depression/ or Treatment Resistant Depression/ 7 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 8 or/6-7 9 and/5,8 10 exp Measurement/ or exp Attitude Measures/ or exp "Checklist (Testing)"/ or exp Inventories/ or exp Psychological Assessment/ or exp Questionnaires/ or exp Rating Scales/ or exp Screening/ or exp Screening Tests/ or exp Standardized Tests/ or exp "Stress and Coping Measures"/ or exp Testing/ 11 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab. 12 ("Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic 3

Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ-2 or PHQ9 or PHQ-9 or PHQ-ADS or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self-rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).tm. 13 exp Treatment/ 14 exp Behavior Modification/ or exp Behavior Therapy/ or Biofeedback Training/ or Contingency Management/ or Self-management/ or Anxiety Management/ or Cognitive Therapy/ or Readiness to Change/ or Relaxation Therapy/ or Self-help Techniques/ or Self-monitoring/ or Stress Management/ 15 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab. 16 Antidepressant Drugs/ or Serotonin Norepinephrine Reuptake Inhibitors/ or Serotonin Reuptake Inhibitors/ or Tricyclic Antidepressant Drugs/ or Bupropion/ or Citalopram/ or Fluoxetine/ or Fluvoxamine/ or "Hydroxytryptophan (5-)"/ or MAPROTILINE/ or Mianserin/ or Paroxetine/ or RITANSERIN/ or Sulpiride/ or Trazodone/ or Tryptophan/ or Venlafaxine/ 17 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab. 18 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab. 19 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog* or coping or psychosocial* or psycho-social* or "social support" or "social work*" or stress).ti,ab. 20 exp Exercise/ 21 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab. 22 Music Therapy/ 23 music therapy.ti,ab. 24 or/10-23 25 and/9,24 26 limit 25 to english language

Embase.com Date search: June 24, 2020 # Search #26 #25 AND [embase]/lim NOT ([embase]/lim AND [medline]/lim) #25 #9 AND #23 AND [english]/lim #24 #9 AND #23 #23 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 #22 'music therapy':ti,ab,kw #21 'music therapy'/de #20 (((aerobic OR resistance) NEAR/2 (exercis* OR program* OR therap* OR train*)):ti,ab,kw) OR ((exercise NEAR/2 (program* OR therap* OR train*)):ti,ab,kw) OR 'cross training':ti,ab,kw #19 'kinesiotherapy'/de OR 'resistance training'/de #18 nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmacolog*:ti,ab,kw OR 'non pharmacolog*':ti,ab,kw 4

#17 amitriptyline:ti,ab,kw OR amoxapine:ti,ab,kw OR clomipramine:ti,ab,kw OR desipramine:ti,ab,kw OR dothiepin:ti,ab,kw OR doxepin:ti,ab,kw OR imipramine:ti,ab,kw OR iprindole:ti,ab,kw OR lofepramine:ti,ab,kw OR nortriptyline:ti,ab,kw OR opipramol:ti,ab,kw OR protriptyline:ti,ab,kw OR trimipramine:ti,ab,kw OR gabapentin:ti,ab,kw OR sildenafil:ti,ab,kw OR vardenafil:ti,ab,kw #16 'tricyclic antidepressant agent'/de OR 'amitriptyline'/de OR 'clomipramine'/de OR 'desipramine'/de OR 'dosulepin'/de OR 'doxepin'/de OR 'imipramine'/de OR 'iprindole'/de OR 'lofepramine'/de OR 'nortriptyline'/de OR 'opipramol'/de OR 'protriptyline'/de OR 'trimipramine'/de #15 ((antidepress*:ti,ab,kw OR 'anti depress*':ti,ab,kw OR '5 hydroxytryptophan':ti,ab,kw OR amisulpride:ti,ab,kw OR bupropion:ti,ab,kw OR citalopram:ti,ab,kw OR escitalopram:ti,ab,kw OR fluoxetine:ti,ab,kw OR fluvoxamine:ti,ab,kw OR maprotiline:ti,ab,kw OR mianserin:ti,ab,kw OR paroxetine:ti,ab,kw OR quipazine:ti,ab,kw OR ritanserin:ti,ab,kw OR sulpiride:ti,ab,kw OR trazodone:ti,ab,kw OR tryptophan:ti,ab,kw OR 'venlafaxine hydrochloride':ti,ab,kw OR viloxazine:ti,ab,kw OR ssri:ti,ab,kw OR ssris:ti,ab,kw OR 'selective serotonin reuptake':ti,ab,kw OR 'selective serotonin re-uptake':ti,ab,kw OR snri:ti,ab,kw OR snris:ti,ab,kw OR serotonin:ti,ab,kw) AND 'noradrenaline reuptake inhibitor':ti,ab,kw OR serotonin:ti,ab,kw) AND 'noradrenaline reuptake inhibitors':ti,ab,kw OR nri:ti,ab,kw OR nris:ti,ab,kw OR 'norepinephrine reuptake inhibitor':ti,ab,kw OR 'norepinephrine reuptake inhibitors':ti,ab,kw #14 'antidepressant agent'/de OR 'serotonin uptake inhibitor'/de OR 'serotonin noradrenalin reuptake inhibitor'/de OR 'adrenergic receptor affecting agent'/de OR '5 hydroxytryptophan'/de OR 'amisulpride'/de OR 'amfebutamone'/de OR 'citalopram'/de OR 'fluoxetine'/de OR 'fluvoxamine'/de OR 'maprotiline'/de OR 'mianserin'/de OR 'paroxetine'/de OR 'quipazine'/de OR 'ritanserin'/de OR 'sulpiride'/de OR 'trazodone'/de OR 'tryptophan'/de OR 'venlafaxine'/de OR 'viloxazine'/de #13 'cognitive behavior*':ti,ab,kw OR 'cognitive behaviour*':ti,ab,kw OR intervention:ti,ab,kw OR interventions:ti,ab,kw OR nondrug:ti,ab,kw OR 'non drug':ti,ab,kw OR nonpharmac*:ti,ab,kw OR 'non pharmac*':ti,ab,kw OR pharmac*:ti,ab,kw OR program*:ti,ab,kw OR psych*:ti,ab,kw OR psychosocial:ti,ab,kw OR 'psycho social':ti,ab,kw OR rehabilitation:ti,ab,kw OR therapy:ti,ab,kw OR therapies:ti,ab,kw OR treat*:ti,ab,kw #12 'behavior therapy'/de OR 'cognitive behavioral therapy'/de OR 'mental health service'/de OR 'psychotherapy'/de OR 'psychosocial care'/de OR 'social support'/de OR 'motivational interviewing'/de OR 'patient participation'/de #11 (checklist*:ti,ab,kw OR 'check list*':ti,ab,kw OR questionnaire:ti,ab,kw OR questionnaires:ti,ab,kw OR instrument:ti,ab,kw OR instruments:ti,ab,kw OR inventory:ti,ab,kw OR inventories:ti,ab,kw OR scale:ti,ab,kw OR scales:ti,ab,kw OR schedule:ti,ab,kw OR schedules:ti,ab,kw OR screen:ti,ab,kw OR screened:ti,ab,kw OR screening:ti,ab,kw OR 'beck depression':ti,ab,kw OR bdi:ti,ab,kw OR bdi2:ti,ab,kw OR 'geriatric depression scale':ti,ab,kw OR gds:ti,ab,kw OR 'hamilton rating scale for depression':ti,ab,kw OR 'hospital anxiety':ti,ab,kw) AND 'depression scale':ti,ab,kw OR hads:ti,ab,kw OR 'kidney disease quality of life':ti,ab,kw OR kdqol:ti,ab,kw OR 'medical outcomes study short form health survey 36':ti,ab,kw OR 'mos sf36':ti,ab,kw OR 'minnesota multiphasic personality inventory':ti,ab,kw OR mmpi:ti,ab,kw OR 'multiple affect adjective check list':ti,ab,kw OR maacl:ti,ab,kw OR 'patient health questionnaire':ti,ab,kw OR phq2:ti,ab,kw OR 'phq 2':ti,ab,kw OR phq9:ti,ab,kw OR 'phq 9':ti,ab,kw OR 'prime-md':ti,ab,kw OR 'epidemiologic studies depression scale':ti,ab,kw OR ced:ti,ab,kw OR cesd:ti,ab,kw OR bref:ti,ab,kw OR dass21:ti,ab,kw OR idid:ti,ab,kw OR 'quick inventory of depressive symptomatology self-report':ti,ab,kw OR 'qids sr':ti,ab,kw OR 'rand 36‐item health survey':ti,ab,kw OR 'rand 36':ti,ab,kw OR 'short form 36':ti,ab,kw OR 'sf 36':ti,ab,kw OR 'structured clinical interview':ti,ab,kw OR scid:ti,ab,kw OR 'self-rating depression scale':ti,ab,kw OR sds:ti,ab,kw OR 'short form health survey 36':ti,ab,kw OR sf36:ti,ab,kw #10 'brief psychiatric rating scale'/de OR 'diagnostic procedure'/de OR 'neuropsychological test'/de OR 'patient health questionnaire'/de OR 'psychological rating scale'/de OR 'psychologic test'/de OR 'questionnaire'/de #9 #5 AND #8 #8 #6 OR #7 #7 depressed:ti,ab,kw OR depressive:ti,ab,kw OR depression*:ti,ab,kw OR suicidal:ti,ab,kw OR suicide:ti,ab,kw OR suicides:ti,ab,kw #6 'depression'/exp #5 #1 OR #2 OR #3 OR #4 #4 dialysis:ti,ab,kw OR haemodiafiltration:ti,ab,kw OR hemodiafiltration:ti,ab,kw OR 'haemo diafiltration':ti,ab,kw OR 'hemo diafiltration':ti,ab,kw OR haemofiltration:ti,ab,kw OR hemofiltration:ti,ab,kw OR 'haemo filtration':ti,ab,kw OR 'hemo filtration':ti,ab,kw OR haemodialysis:ti,ab,kw OR hemodialysis:ti,ab,kw OR 'haemo dialysis':ti,ab,kw OR 'hemo dialysis':ti,ab,kw 5

#3 'hemodialysis'/exp OR 'hemofiltration'/exp OR 'hemodiafiltration'/exp OR 'peritoneal dialysis'/exp #2 (((chronic OR endstage OR 'end stage' OR endstate OR 'end state' OR failure OR 'long term' OR maintenance) NEAR/2 (kidney OR renal)):ti,ab,kw) OR eskd:ti,ab,kw OR eskf:ti,ab,kw OR esrd:ti,ab,kw OR esrf:ti,ab,kw #1 'chronic kidney failure'/exp

EBM Reviews: Cochrane Central Register of Controlled Trials June 2020 Cochrane Database of Systematic Reviews 2005 to June 24, 2020 Database of Abstracts of Reviews of Effects 1st Quarter 2016 Health Technology Assessment 4th Quarter 2016 Date searched: June 24, 2020 # Searches 1 (((chronic or endstage or end-stage or endstate or end-state or failure or long-term or maintenance) adj2 (kidney or renal)) or ESKD or ESKF or ESRD or ESRF).ti,ab. 2 (dialysis or haemodiafiltration or hemodiafiltration or haemo-diafiltration or hemo-diafiltration or haemofiltration or hemofiltration or haemo-filtration or hemo-filtration or haemodialysis or hemodialysis or haemo-dialysis or hemo-dialysis).ti,ab. 3 or/1-2 4 (depressed or depressive or depression* or suicidal or suicide or suicides).ti,ab. 5 and/3-4 6 (checklist* or check-list* or questionnaire or questionnaires or instrument or instruments or inventory or inventories or scale or scales or schedule or schedules or screen or screened or screening or "Beck Depression" or BDI or BDI2 or "geriatric depression scale" or GDS or "Hamilton Rating Scale for Depression" or "Hospital Anxiety and Depression Scale" or HADS or "Kidney Disease Quality of Life" or KDQOL or "Medical Outcomes Study Short Form Health Survey 36" or MOS-SF36 or "Minnesota Multiphasic Personality Inventory" or MMPI or "Multiple Affect Adjective Check List" or MAACL or "Patient Health Questionnaire" or PHQ2 or PHQ- 2 or PHQ9 or PHQ-9 or "PRIME-MD" or "Epidemiologic Studies Depression Scale" or CED or CESD or BREF or DASS21 or IDID or "Quick Inventory of Depressive Symptomatology Self-Report" or QIDS-SR or "RAND 36‐ Item Health Survey" or RAND-36 or "short form 36" or SF-36 or "Structured Clinical Interview" or SCID or "self- rating depression scale" or SDS or "Short Form Health Survey 36" or SF36).ti,ab. 7 (cognitive-behavior* or cognitive-behaviour* or intervention or interventions or nondrug or non-drug or nonpharmac* or non-pharmac* or pharmac* or program* or psych* or psychosocial or psycho-social or rehabilitation or therapy or therapies or treat*).ti,ab. 8 (antidepress* or anti-depress* or 5-hydroxytryptophan or Amisulpride or Bupropion or Citalopram or Escitalopram or Fluoxetine or Fluvoxamine or Maprotiline or Mianserin or Paroxetine or Quipazine or Ritanserin or Sulpiride or Trazodone or Tryptophan or Venlafaxine Hydrochloride or Viloxazine or SSRI or SSRIs or "selective serotonin reuptake" or "selective serotonin re-uptake" or SNRI or SNRIs or "Serotonin and Noradrenaline Reuptake Inhibitor" or "Serotonin and Noradrenaline Reuptake Inhibitors" or NRI or NRIs or "norepinephrine reuptake inhibitor" or "norepinephrine reuptake inhibitors").ti,ab. 9 (Amitriptyline or Amoxapine or Clomipramine or Desipramine or Dothiepin or Doxepin or Imipramine or Iprindole or Lofepramine or Nortriptyline or Opipramol or Protriptyline or Trimipramine or Gabapentin or Sildenafil or Vardenafil).ti,ab. 10 (nondrug or non-drug or nonpharmacolog* or non-pharmacolog*).ti,ab. 11 (((aerobic or resistance) adj2 (exercis* or program* or therap* or train*)) or (exercise adj2 (program* or therap* or train*)) or cross-training).ti,ab. 12 music therapy.ti,ab. 13 or/6-12 14 and/5,13

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ClinicalTrials.gov Date searched: June 24, 2020 ( depressed OR depressive OR depression* OR suicidal OR suicide OR suicides ) AND INFLECT EXACT ( "Active, not recruiting" OR "Completed" OR "Suspended" OR "Terminated" OR "Withdrawn" OR "Unknown status" ) [OVERALL-STATUS] AND ( ( chronic OR endstage OR end-stage OR failure ) AND ( kidney OR renal ) OR ESKD OR ESKF OR ESRD OR ESRF OR dialysis OR haemodiafiltration OR hemodiafiltration OR haemo-diafiltration OR hemo-diafiltration OR haemofiltration OR hemofiltration OR haemo-fi ) [DISEASE]

WHO ICTRP Date searched: June 24, 2020 (((chronic OR endstage OR end-stage OR failure) AND (kidney OR renal)) OR ESKD OR ESKF OR ESRD OR ESRF) AND (depress* OR suicid*)

VA HSR&D https://www.hsrd.research.va.gov/research/ Date searched: June 24, 2020 Separately searched terms: kidney and renal. Reviewed result lists

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Item S2. Study Selection Criteria (Parent VA Review)

Inclusion/Exclusion Criteria for Full Text Review 1. Language: Is the full text of the article in English? Yes...... …...... ……...... …...... Proceed to #2 No ...... ………...... …………….………………Code X1. STOP

2. Population: Does the study include adults with ESRD or CKD (or CKF, CRF) undergoing maintenance dialysis? Yes …………………………………………………….………………………….Proceed to #3 No ……Code X2. Add code B (example: X2 – B) if retaining for background/discussion. STOP

3. Population: Does the study include adults screened, diagnosed with, or treated for depression? Yes………………...... ……………...... …...... Proceed to #4 No… ……………………..Code X2. Add code B if retaining for background/discussion. STOP

4. KQ1: Does the study examine screening tool(s) for depression? Yes………………...... ……………...... …...... Proceed to Q5 No ………………………………………………………...……...Code 0 for KQ1. Proceed to Q6

5. KQ1: Does the study compare a screening tool against the gold standard (e.g., clinical interview – e.g., SCID) or another validated depression assessment tool? Yes, gold standard (e.g., clinician interview/SCID)…Code I for "I or X Code" and 1 for KQ1. STOP Yes, another depression tool…………...Code I for "I or X Code" and 1 - Tool for KQ1. STOP No ………………………………………………………...…Proceed to Q6 (and code 0 for KQ1)

6. Study Design: Is the study original quantitative research, a systematic review (SR) or meta- analysis (MA; exclude other literature reviews, editorials, qualitative research, etc.)? Yes………………...... ……………...... …. If SR or MA code X3 - PEARL. If other quantitative, Proceed to Q7 No…….Code X3. Add code B (example: X3 – B) if retaining for background/discussion. Code 0 for all KQs. STOP

7. Comparator: The study has a comparison group (other screening tool, no screening, other intervention, waitlist controls, etc.). Pre-post studies are excluded. Yes …………………………………………………….…………………………. Proceed to Q8 No...…Code X4. Add code B if retaining for background/discussion. Code 0 for all KQs STOP

8. Outcomes: Does the study report 1 or more of the following outcomes specifically for the population of interest (ESRD/CKD maintenance dialysis) Diagnostic test performance: sensitivity, specificity, positive predictive value, and negative predictive value; Therapeutic impact: timing, setting, or type of treatment.; Intermediate and Patient outcomes: depressive symptoms, mortality, suicide attempts or completion, hospitalization, ED/urgent care utilization, patient satisfaction, adherence to dialysis, medication, or treatment, pain medication reduction, BP/metabolic control, quality of life, other outcomes (e.g., employment); Adverse effects or unintended consequences. Prevalence and correlational studies are excluded. Yes …………………………………………………….……………….……………Proceed to Q9 No.……Code X5. Add code B if retaining for background/discussion. Code 0 for all KQs STOP 8

9. Does the article or main study (from which the data were gathered) examine the impact of screening or the effectiveness of treatment for depression (including subgroup differences or harms)? Yes, screening ……………………………………………………………………..Proceed to Q10 Yes, treatment: Is depression an inclusion criterion, or is the average depression score of participants equivalent to at least moderate depression? (Cutoffs: PHQ-9 ≥ 10;1 CES-D ≥ 18;2 HAM- D ≥ 12;3 BDI-II ≥ 16;2,3 BDI-II ≥ 13;3 HADS ≥ 84,5) No…………………………………………………………………………………Code X2 Yes…………………………………………………………………………Proceed to Q10 No ………………………….Code X5. Add code B if retaining for background/discussion. STOP

10. Harms: Does the article examine the harms of screening or treatment? Yes………………………………….Code I for "I or X Code" and 1 for KQ4. Proceed to Q11. No………………………………………………………………Code 0 for KQ4. Proceed to Q11.

11. Study Design: Does the article describe data collected as part of an RCT or NRCT? Yes…………………………………………………….………………………….Proceed to Q12. No………………………………………………………..Code X3. Code 0 for KQs 2, 3. STOP.

12. KQs 2 and 3: Does the study examine the impact of screening or treatment? Yes………………………………Code I for "I or X Code" and 1 for KQ2 if screening and/or 1 for KQ3 if treatment. Code 0 for KQ 2 or 3 if NA. STOP. No…………………………………………………….…………Code 0 for KQs 2 and 3. STOP. All articles should have at least 1 code. If not, re-review. Be sure that all articles are coded 0 for all KQs that are not relevant.

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Table S1. PICOTS by Key Question

Key Question: KQ1: What is the effectiveness of depression KQ2: In patients with KQ3: Do the benefits or harms of treatment differ by: treatment in patients with ESRD and ESRD, what are the a. patient characteristics or other social determinants of depression: potential harms of health? a. pharmacological? treatment for depressed b. setting? b. non-pharmacological? patients? c. provider characteristics (e.g., mental health, PCP)? c. pharmacological and non-pharmacological i. pharmacological? d. other (e.g., patient engagement/ receptivity to treatment, treatments combined? ii. non-pharmacological? social support)? e. timing and type of follow up?

Population Adults with ESRD and depression (Cutoffs: PHQ-9 ≥ 10;1 CES-D ≥ 18;2 HAM-D ≥ 12;3 BDI-II ≥ 16;2,3 BDI ≥ 13;3 HADS ≥ 84,5). If study specified inclusion of subclinical or mild depression in eligibility criteria, we excluded it. Intervention Pharmacological (4+ weeks) and non-pharmacological treatments for depression Comparators Placebo, waitlist control, other intervention Outcomes Intermediate and Patient outcomes: depressive Adverse effects or Intermediate and Patient outcomes: depressive symptoms, symptoms, mortality, suicide attempts or unintended consequences mortality, suicide attempts or completion, hospitalization, completion, hospitalization, ED/urgent care ED/urgent care utilization, patient satisfaction, adherence to utilization, patient satisfaction, adherence to dialysis, medication, or treatment, pain medication dialysis, medication, or treatment, pain reduction, BP/metabolic control, quality of life, other medication reduction, BP/metabolic control, outcomes (e.g., employment) quality of life, other outcomes (e.g., employment) Timing Any Settings All settings in U.S. or international (VHA, hospital community, community mental health, ED, urgent care, other community) Study design Systematic reviews, RCTs, NRCTs Systematic reviews, RCTs, NRCTs, Observational studies Note. Subpopulations may include: Patient demographic characteristics or social determinants of health; treated by HD (home or clinic); treated by PD (home or clinic); clinical severity (ESRD or depression); setting (e.g. 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

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Table S2. Strength of Evidence Domains and Grading

Strength of Evidence Domains Study Limitations Directness Consistency Precision Reporting Bias (Internal Validity) • Direct: the evidence links • Degree to which • Degree of certainty • Publication bias: • Degree to which intervention to a health outcome included studies surrounding an effect nonreporting of the full the include • Indirect: only intermediate find either the estimate with respect study studies for a outcomes are available same direction or to a given outcome • Selective outcome given outcome (e.g., lab tests) when similar magnitude based on the reporting bias: have a high outcomes of interest are of effect sufficiency of sample nonreporting or likelihood of health outcomes (e.g., • Direction of effect: size and number of incomplete reporting of adequate mortality effect sizes have events planned outcomes or protection against • Indirect: data come from proxy the same sign (are • In a meta-analysis, reporting of unplanned bias assessed respondents on the same side of consider whether the outcomes through: • Indirect: data do not come from no effect or a MID) CI crossed a • Selective analysis o Study Design head-to-head comparisons but • Magnitude of threshold for a MID reporting bias: reporting o Study Conduct from two or more bodies of effect: The range of • Consider the of one or more favorable evidence effect sizes is narrowness of analyses for a given similar (may individual study CI outcome while not Indirectness implies that more consider overlap in ranges or reporting other, less than one body of evidence is confidence significance of p- favorable analyses required to link evidence to the intervals) values in evidence most important health outcomes. base Strength of Evidence Grades Low Insufficient Moderate High We have limited confidence that the We have no evidence, we are We are moderately confident We are very confident that the estimate of effect lies close to the true unable to estimate an effect, or that the estimate of effect lies estimate of effect lies close to effect for this outcome. we have no confidence in the close to the true effect for this the true effect for this

estimate of effect for this outcome. outcome. The body of evidence has major or outcome. numerous deficiencies (or both). We The body of evidence has The body of evidence has few believe that additional evidence is No evidence is available, or the some deficiencies. We believe or no deficiencies. We believe needed before concluding either that body of evidence has that the findings are likely to that the findings are stable, the findings are stable or that the unacceptable deficiencies, be stable, but some doubt that is, another study would estimate of effect is close to the true precluding reaching a conclusion. remains. not change the conclusions. effect. Abbreviations: CI = confidence interval; MID = minimum important difference; SOE = strength of evidence Note: This table provides a summary of the elements described in Berkman and colleagues, 20156

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References

1. Department of Veterans Affairs, Department of Defense. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder. 2016;Verson 3.0. 2. CMS Center for Clinical Standards & Quality. Summary of Representative Clinical Depression Screening Tools. November 30, 2015. 3. Furukawa TA, Reijnders M, Kishimoto S, et al. Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking. Epidemiol Psychiatr Sci. 2019:1-13. 4. Stafford L, Berk M, Jackson HJ. Validity of the Hospital Anxiety and Depression Scale and Patient Health Questionnaire-9 to screen for depression in patients with coronary artery disease. Gen Hosp Psychiatry. 2007;29(5):417-424. 5. Applied Health Sciences (Mental Health). Assessing the validity of the PHQ-9, HADS, BDI-II and QIDS-SR in measuring severity of depression in a UK sample of primary care patients with a diagnosis of depression. University of Aberdeen. 2011. 6. Berkman ND, Lohr KN, Ansari MT, et al. Grading the strength of a body of evidence when assessing health care interventions: an EPC update. J Clin Epidemiol. 2015;68(11):1312-1324.

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