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 Randomized; Years of EnrollmentIntervention/ComparatorN Sites; Study Setting; Country/US RegionClinical Characteristics/Demographics of Study PopulationInclusion CriteriaDepression Screening Tool(s)Baseline Depression Score, Mean (SD), T versus C
Pharmacologic
 Blumenfield et al. (30); N=14; Yr NRFluoxetine versus placebo2 sites; hospital dialysis centers; New York, NYNRCutoff for inclusion: HAM-D score ≥16HAM-D; BDI-II; MADRS; BSI; VASNR
Other inclusion criteria: age 18–70, normal liver function
 Friedli et al. (33); N=30; April 2013–May 2015aSertraline versus placeboMultisite (5); renal units; England12% Female; age (SD), 61.7 (13.2) yr; race, 67% White, 13% Black, 13% Asian, 7% mixedCutoff for inclusion: BDI-II score ≥16, MINI mild to moderate MDD, MADRS score ≥18BDI-II; MINI; MADRSMADRS: 24.5 (4.5) versus 25.3 (4.2)
Other inclusion criteria: excluded if already on SSRIs (56)
 Gharekhani et al. (35); N=54; Yr NRΩ-3 Fatty acid versus placebo2 sites; HD centers; Tehran, IranHD duration (SD), 70.7 (45.1) mo, 4 h, 2–3× per wk; 48% female; age (SD), 56.8 (13.09) yrCutoff for inclusion: BDI-II score ≥16BDI-II23.52 (7.49) versus 21 (4.72); median (IQR): 22 (17–28) versus 21 (16.50–22.75)
Other inclusion criteria: adults, HD ≥3 mo and all had same HD Rx
 Haghighat et al. (36); N=49; Yr NRSynbiotic supplement versus probiotic; supplement versus placebo1 site; hospital HD center; Iran52% Female; age (SD), 46.64 (10.69) yrCutoff for inclusion: ≥8HADS9.16 (1.11) versus 9.77 (1.77) versus 9.20 (1.30); P=0.63
Other inclusion criteria: stable patient on HD with arteriovenous fistula, age 30–65, HD 3× per wk for ≥3 mo
 Hosseini et al. (38); N=44; Yr NRCitalopram versus psychologic trainingSingle site; hospital HD center; Iran55% Female; age (SD), 52.3 (15.6) yrCutoff for inclusion: HADS ≥8HADS9.42 (3.11) versus 9.58 (3.47)
Other inclusion criteria: NA
 Mehrotra et al. (44); N=120; 2017Sertraline versus CBTMultisite (3 states); 41 dialysis facilities; United States, NM, TX, WAMedian time on dialysis, 31 mo; mean HD session length (SD), 3.9 (0.4) h; history of major depression, 42%; 43% female; age (SD), 51 (13) yr; race/ethnicity, 43% White, 28% Black, 28% Hispanic, 8% Native American, 12% other; education, 40% ≤high schoolCutoff for inclusion: BDI-II ≥15, then confirmed by MINIBDI-II; MINI; QIDS-SR; QIDS-CQIDS-C mean (range): SERT 10.9 (9.6–12.1) versus CBT 12.2 (11.0–13.5)
Other inclusion criteria: age ≥21, ESKD, on HD for ≥3 moBDI-II mean (range): SERT 25.8 (23.3–28.4) versus CBT 26.2 (23.6–28.8)
 Taraz et al. (46);
N=50;
Yr NR
Sertraline versus placeboSingle site; outpatient HD clinic; Tehran, IranHD for 4 h 3× per wk, 43%; time on HD, 42 mo; 59% female; age (SD), 60 (22) yr; all others NRCutoff for inclusion: BDI-II ≥16BDI-II29 (13) versus 23 (11); P=0.24
Other inclusion criteria: age 18–80, HD ≥3 mo using arteriovenous fistula
 Wang et al. (49); N=160; 2013Radix Bupleuri herbal supplement versus placeboSingle site; Dalian, Northeast ChinaHD duration (SD), 26 (13) versus 29 (15) mo; 75% female; education, approximately 86% <9 yr; concurrent antidepressant medication use, 51% versus 46%Cutoff for inclusion: NRMADRS23.9 (7.8) versus 24.6 (7.4)
Other inclusion criteria: aged 30–55 yr; no history of repeated suicidal behavior, severe substance abuse, severe depression impairing verbal abilities, family history of depression, or brain injury/disease
 Wang et al.(50); N=746; Yr NRVitamin D3 versus placebo3 sites; dialysis centers, HD and PD, outpatient; Southeast China39% Female; age, 54% 18–64 yr; 46% ≥65 yr; other demographics, NRCutoff for inclusion: BDI-II ≥16BDI-II22.7 (4.3) versus 21.9 (5.4); P=0.31
Other inclusion criteria: ESKD, current conventional maintenance PD (three exchanges per day) or HD (3× 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); N=130; 2017CBT versus PSEMultisite; 5 hospital dialysis units; JordanDialysis duration, NR; approximately 50% female; age (SD), 52 (10.7) yr; education, 71% ≤high school; employment, 82% unemployed; race/insurance, NRCutoff for inclusion: NRHAM-DPSE 19.6 (5.4) versus CBT 19.5 (5.4); no difference, t (103)=−0.13; P=0.89
Other inclusion criteria: diagnosis of chronic kidney failure, chronic dialysis ≥1 yr, verbal comprehension/communication
 Babamohamadi et al. (28); N=60; Yr NRQuran versus TAUSingle site; hospital dialysis ward; Iran43% Female; age (SD), 53.3 (11.4) yr; race, NR; education, 75% less than diploma; employment, NR (56% “poor”); insurance, NRCutoff for inclusion: BDI-II score ≥20BDI-II33.6 (6.7) versus 29.3 (9.0); mean difference, -4.3 (95% CI, −8.7 to 0.0); P=0.05
Other inclusion criteria: age 18–65, command of Arabic, HD for ≥6 mo, hemodynamically stable
 Beizaee et al. (29); N=80; 2015–2016Guided imagery versus TAUSingle site; HD center; Iran41% Female; age (SD), 47.21 (8.34) yr; education, 46% secondary school; employment, 25% unemployedCutoff for inclusion: NRHADS10.82 (2.70) versus 11.55 (2.29)
Other inclusion criteria: HD 3× per wk for ≥6 mo, age 35–65 yr, read/write in Farsi, intact cognitive functions on the basis of AMT
 Cukor et al. (31); N=65; Yr NRCBT versus wait list2 sites; dialysis units; Brooklyn, NY73% Female; age, NR; race, 94% Black; education (SD), 11.2 (3.4) yr; employment, 83% unemployed; insurance, NRCutoff for inclusion: BDI-II score ≥10SCID-I; BDI-II; HAM-DSCID-I with major depression: 55% versus 42%
Other inclusion criteria: ESKD with HD for ≥6 moBDI-II: 25.3 (9.3) versus 21.4 (8.9)
HAM-D: 15.0 (6.2) versus 13.5 (5.0)
 Duarte et al. (32); N=90; Yr NRCBT versus psychotherapy2 sites; dialysis units; BrazilHD, 3× per wk for 4 h average; 63% female; age (SD), 52.4 (15.9) yr; race, 78% White; education, 83% ≤primary school; employment/insurance, NRCutoff for inclusion: MDD with MINIBDI-II; MINIBDI-II: 24.2 (9.7) versus 27.3 (10.7); P=0.15
Other inclusion criteria: ESKD with HD for ≥3 moMINI: 6.4 (1.3) versus 6.4 (1.2); P=0.96
 Frih et al. (34); N=41; 2012–2013aExercise (endurance-resistance training) versus TAUSingle site; hospital; TunisiaHD, 4 h 3×/wk; HD duration, 72.7 (12.7) mo; age (SD), 64.2 (3.4) yr; 0% female; other demographics, NRCutoff for inclusion: NRHADSApproximately 12 versus approximately 13 (exact scores NR)
Other inclusion criteria: excluded chronic lung disease, ischemic heart disease, uncontrolled arrhythmias or hypertension, hemodynamically unstable, or musculoskeletal disorders, those regularly exercising
 Heshmatifar et al. (37); N=70; 2013Benson relaxation technique versus TAUSingle site; hospital HD unit; IranHD, 3× per wk; 18% female; age, 9% 18–35, 33% 35–45, 45% 45–55, 15% 55–65 yr; race, NR; education, 94% ≤high school; employment, 42% unemployed; insurance, NRCutoff for inclusion: NRBDI-II32.46 (9.86) versus 30.58 (9.24)
Other inclusion criteria: aged 18–65 yr, HD 3× per wk for ≥6 mo, regular patient of the center
 Kargar Jahromi et al. (55); N=60; 2014Telenursing versus TAUSingle site; hospital HD unit; IranT versus C:56% versus 40% female; education, 4% >high school; unemployed, 60% versus 44%; other demographics, NRCutoff for inclusion: NRDASS-2116.60 (1.50) versus 16.72 (1.83); P=0.40
Other inclusion criteria: aged 18–65 yr; HD 3–4 h 3× per wk for ≥6 mo; no transplants, hospitalizations, or antidepressant Rx
 Kalani et al. (39); N=96; 2011Acupressure versus sham versus TAU3 sites; HD centers; Iran44% female; age (SD), 53.4 (13.9); race, NR; education, 31% nonliterate; employment, 50% unemployed, 41% retired; insurance, NRCutoff for inclusion: BDI-II score ≥10BDI-IIT 27.5 (9.1) versus sham 25.7 (7.7) versus C 24.6 (8.6)
Other inclusion criteria: ESKD diagnosis, age ≥18, HD for ≥3 mo, mental and psychologic ability to participate
 Kouidi et al. (40); N=50; Yr NRExercise training versus sedentary controlSingle site; hospital renal unit; GreeceHD, 3× per wk for 4 h; 42% female; age (SD), 46.3 (11.2) yr; education, 10.2 (3.4) yr; employment, 17% unemployed; race/insurance, NRCutoff for inclusion: NRBDI-II; HADSBDI-II: 22.29 (6.71) versus 22.30 (6.81)
Other inclusion criteria: ESKD, 4 h HD 3× per wk for ≥6 moHADS: 10.63 (2.60) versus 10.40 (2.50)
 Lerma et al. (41); N=60; Yr NRCBT versus waiting list2 sites; HD units; Mexico City, MexicoHD, 3× per wk for 3–4 h; 52% female; age (SD), 41.8 (14.7) yr; education, 36% elementary; employment, 26% unemployed; race/insurance, NRCutoff for inclusion: BDI-II score of 10–29 pointsBDI-II13.6 (7.6) versus 15.8 (10.0)
Other inclusion criteria: ESKD, literate, no psychiatric illness, regular attendance of HD sessions 3–4 h HD 3× per wk for ≥6 mo
 Li et al. (42); N=72; 2018–2019Home nursing visits versus telephone follow-upSingle site; hospital; Hainan, ChinaDialysis duration (SD), 22.68 (10.25) mo; 44% female; age (SD), 55.8 (6.2) yr; education, 56% ≤middle schoolCutoff for inclusion: NRZung SDS63.34 (6.28) versus 64.27 (6.11); P=0.53
Other inclusion criteria: age 30–80, on home PD ≥3 mo, kidney failure
 Liao et al. (43); N=128; 2017Comprehensive nursing versus conventional careSingle site; hospital; Hainan, ChinaHD duration (SD), 43.56 (13.95) mo; 44% female; age (SD), 52.87 (10.46) yr; education, 57% <high schoolCutoff for inclusion: NRZung SDS60.83 (22.67) versus 64.02 (28.58); P=0.49
Other inclusion criteria: age ≥18, on HD ≥3 mo for CRF/ESKD
 Rahimipour et al. (45); N=50; Yr NRHope therapy versus controlMultisite; hospitals; IranHD, 2–3× per wk for 4 h; 48% female; age (SD), 47.82 (15.12) yr; race/education/employment/insurance, NRCutoff for inclusion: NRDASS-2113.36 (3) versus 13.64 (3.5); P=0.76
Other inclusion criteria: aged 18–65 yr; HD 2–3× per wk for ≥3 mo; not taken medication for depression, anxiety, or stress
 Thomas et al. (47); N=41; 2016MBSR versus TAUSingle site; hospital HD unit; Montreal, Canada33% Female; age (SD), 65 (13) yr; race, 49% White, 51% non-White; education, 63% ≤ high school; employment/insurance, NRCutoff for inclusion: PHQ-9 score ≥6 and/or GAD-7 score ≥6PHQ-912.7 (4.2) versus 11.9 (5.8)
Other inclusion criteria: on maintenance HD, spoke English or French
 Tsay et al. (48); N=108; Yr NRAcupressure versus TEAS versus control4 sites; hospital dialysis centers; Northern TaiwanDuration HD (SD), 50.06 (44.15) mo; 66% female; age (SD), 58.16 (12.19) yr; employment, 76% retired or unemployed; race/education, NRCutoff for inclusion: BDI-II score ≥10BDI-IIAcupressure 20.37 (10.65) versus TEAS 18.20 (11.11) versus C 21.61 (11.69)
Other inclusion criteria: ESKD diagnosis, age ≥18, HD for ≥3 mo, fatigue, PSQI score ≥5
 Widyaningrum and Djarwoto (51); N=36; 2012Latihan Pasrah Diri versus controlSingle site; hospital HD unit; Java, IndonesiaHD 2× per wk; 61% female; age (SD), 50.06 (7.39) yr; education, 78% ≤ high school; insurance, 6% uninsured; employment/race, NRCutoff for inclusion: BDI-II ≥16BDI-II23 (5.34) versus 23.39 (5.02)
Other inclusion criteria: aged 18–60 yr, CKD adults on 2× per wk HD for ≥3 mo
Harms-only studies
 Assimon et al. (57); N=65,654; 2007–2014SSRIs with higher QT-prolonging potentialb versus SSRIs with lower QT-prolonging potentialcUS Renal Data System Database53% Female; age (SD), 67.0 (17.2) yr; race, 36% Black; ethnicity, 19% HispanicInclusion: new SSRI users who received HD during the 180 d before SSRI initiation and had continuous Medicare Part A, B, and D coverage.NANA
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); N=41; 2013–2015aSSRI observationalMultisite; NR; England37% Female; age (SD), 62 (16) yr; race, 27% non-WhiteASSertID study participants who were excluded from the RCT (33) phase because they were already on SSRIsBDI-II, PHQ-9BDI-II: 26
PHQ-9: 12
 Vangala et al. (58); N=54,032; 2009–2015SSRI versus no SSRIUS Renal Data System DatabasePatients versus controls:female, 58% versus 52%; age (SD), 71 (12) versus 61 (14) yr; 29% versus 49% Black; 22% versus 19% Hispanic; 39% versus 25% non-Hispanic WhiteInclusion: Medicare Part D, receipt of a low-income subsidy, RRT start date, demographic data, a Medical Evidence Report from 1995 or later, >90 d HDNANA
  • 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.

  • a Part of the larger ASSertID study.

  • b Citalopram and escitalopram.

  • c Fluoxetine, fluvoxamine, paroxetine, and sertraline.