Table 2.

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

Author (Reference); Year; N Randomized (T versus C); Duration of Treatment and Follow-UpTreatmentComparatorFindings, Treatment versus ComparatorQuality
DepressionOther outcomes
Pharmacologic
 SSRIs versus control
  Blumenfield et al. (30); 1997; 7 versus 7; Tx=8 wk, F/U=8 wkFluoxetine: 20 mg/d for 8 wkMatched placeboMean change from baseline (at 4 wk; at 8 wk):NAPoor
BDI-II: −12 versus −4.17 (P=0.05); −9.57 versus −8.8 (P=0.91)
BSI: −6.29 versus 0.2 (P=0.04); −4.43 versus −3.2 (P=0.88)
HAM-D: no 4 wk assessment; −9.00 versus −7.5 (P=0.72)
MADRS: −7.20 versus −6.75 (P=0.93); −11.14 versus −6.67 (P=0.45)
VAS: −210.0 versus −58.3 (P=0.37); −303.0 versus −140 (P=0.45)
Electronic VAS: −262.4 versus 5.6 (P=0.05); −389.0 versus −87.8 (P=0.13)
  Friedli et al. (33); 2017; 15 versus 15; Tx=6 mo, F/U=6 moaSertraline: 100 mg/d (50 mg/d to start; dose could be increased to maximum at 2 and 4 mo)Matched placeboMADRS between-group difference at 6 mo: −0.67 (95% CI, −5.7 to 4.4)NAFair
Within-groups decrease significant for both groups
Mean change at study end:
MADRS: −14.5 (95% CI, −20.2 to −8.8) versus −14.9 (95% CI, −18.4 to −11.5)
BDI-II: −15.7 (95% CI, −24.3 to −7.1) versus −13.0 (95% CI, 19.6 to −6.4)
  Taraz et al. (46); 2013; 25 versus 25; Tx=12 wk, F/U=12 wkSertraline: 100 mg/d (50 mg/d for first 2 wk)Matched placeboBDI-II scores (SD) for baseline, 6 wk, 12 wk, Δ baseline to 12 wk:sertraline, 29 (13), 21 (11.5), 15 (5.5), −11.3 (5.8) versus placebo, 23 (11), 22.5 (8.5), 22.5 (9), −0.5 (5); comparison Δ baseline to 12 wk between groups, P=0.001NAFair
 SSRIs versus active comparator
  Hosseini et al. (38); 2012; 22 versus 22; Tx=3 mo, F/U=3 moCitalopram: 20 mg/dPsychologic training: six 1-h sessions on kidney-disease education, problem solving, stress management, and muscle-relaxation techniquesPostintervention HADS (SD): 6.26 (4.18) (P=0.001) versus 7.33 (4.80) after training (P=0.04); no difference between groups (P=0.16)NAPoor
Between-groups mean differences also NS (P=0.65)
  Mehrotra et al. (44); 2019; 60 versus 60; Tx=12 wk, F/U=12 wkSertraline: 200 mg/d unless limited by AEs (titration began at 25 mg/d and adjusted each visit)CBT: ten 60-min sessions during HD for 12 wk, adapted for maintenance HD populationQIDS-C scores (SD): 5.9 (4.5) versus 8.1 (5.1)NAFair
Effect estimate: −1.85 (95% CI, −3.55 to −0.16)
BDI-II scores: 14.1 (95% CI, 11.2 to 17.0) versus 18.7 (95% CI, 15.2 to 22.2)
Effect estimate: −2.9 (95% CI, −6.7 to 0.8)
 Supplements versus placebo
  Gharekhani et al. (35); 2014; 27 versus 27; Tx=4 mo, F/U=4 moΩ-3 Fatty acids: 1800 mg/d for 4 moMatched placebo: paraffin oil capsulesMean end of study BDI-II (SD): 13.44 (5.66) versus 20.33 (7.56)NAPoor
Difference (SD): −10.08 (8.07) versus −0.88 (8.41); P=0.001
Within groups: Significant decrease (P<0.001) versus no significant change
  Haghighat et al. (36); 2019; 16 versus 18 versus 15; Tx=12 wk, F/U=12 wkSynbiotic supplement: L. acidophilus strain T16, B. bifidum strain BIA-6, B. lactis strain BIA-7, B. longum strain BIA-8 (2.7×107 CFU/g each) per 5 g sachet + prebiotic (5 g FOS + 5 g GOS + 5 g inulin per three 5 g sachets); probiotic supplement same as above, except prebiotics replaced with placeboMatched placeboEnd-of-treatment HADS-D scores (SD): synbiotic 6.92 (1.27) versus placebo 9.40 (1.5); P<0.001;NAGood
Synbiotic (SD) 6.92 (1.27) versus probiotic 8.48 (1.61); P=0.011
Mean difference in HADS-D scores from baseline: symbiotic, −2.24 (95% CI, −3.29 to −1.38); probiotic, −1.28 (95% CI, −2.05 to −0.53); placebo, 0.20 (95% CI, −0.43 to0.76); P=0.001
Synbiotic versus placebo (post hoc): P<0.001
  Wang et al. (49); 2015; 80 versus 80; Tx and F/U=3 moRadix Bupleuri herbal supplement: 1 g root powder in capsule dailyPlaceboMean (SD) MADRS scores at 3 mo: 13.32 (8.25) versus 16.73 (9.46)QoL (RAND-36): change from baseline 14.21 versus −1.12; MD, −4.61 (95% CI, −11.32 and 2.75); P=0.04Poor
Change from baseline MADRS: −11.36 versus −2.24; Mean difference, 4.72 (95% CI, 0.69 to 9.12); P=0.02
  Wang et al. (50); 2019; 373 versus 373; Tx and F/U=52 wkHigh-dose oral vitamin D3: 52-wk treatment of 50,000 IU/wkMatched placeboNo between-groups difference in Δ valuesNAFair
Within-group BDI-II scores (SD), baseline to end of study: 22.7 (4.3) to 19.6 (3.7) (P=0.02) versus 21.9 (5.4) to 20.8 (5.1) (P=0.03)
Nonpharmacologic
 Cognitive behavioral therapy
  Al Saraireh et al. (27); 2018; 65 versus 65; Tx=12 wk, F/U=12 wkCBT: seven individual 1-h sessions following the traditional CBT sessions protocolPSE: 7 individual 1-h sessionsPost-test HAM-D scores (SD): 15.0 (5.5) versus 11.1 (2.3)NAPoor
Between-groups depression scores favored PSE (t=4.68; P<0.01) over CBT
  Cukor et al. (31) (crossover); 2014; 38 versus 27; Tx=3 mo, F/U=6 moCBT: individual 60-min CBT chairside during dialysis; modified for population; 10 sessions over 3 moWait-list controlBDI-II: mean change score (SD) during treatment:−11.7 (1.5) points (P<0.001) versus −4.8 (1.4) points (P<0.001)QoL: treatment effect, +12.0 (SD, 3.4; P=0.003) points versus +11.3 points (SD, 3.7; P=0.01)Fair
Raw mean (SD) change: 24.7 (9.8) to 11.7 (9.8) versus 14.5 (8.5) to 9.1 (6.5)Raw mean (SD) score change: 99.5 (27.9) to 115.3 (25.5) versus 110.6 (25.1) to 119.7 (24.7); P=0.04
Mean (SD) change in BDI-II score in untreated group during wait-list period: −6.7 (1.7) points; P<0.001 (raw mean change, 21.9 [8.9] to 14.5 [8.5]).
Magnitude of improvement greater in the intervention-first group versus wait-list condition (P=0.03)Fluid adherence: model-estimated mean change score (SD) during treatment −1.3% (0.3) Δkg/d (P=0.001) versus −1.1% (0.3) Δkg/d (P=0.001)
HAM-D: the difference in mean change score between treated and untreated groups was highly significant (P<0.001)Raw mean (SD) change: 4.0 (2.0) to 2.8 (1.6) versus 3.6 (2.0) to 2.5 (2.0); P=0.002
SCID-I: between groups not reported
  Duarte et al. (32); 2009; 46 versus 44; Tx=12 wk, F/U=9 moCBT: group CBT sessions, 90 min 1× per wk for 12 wk, followed by 6 mo maintenance with monthly meetingsIndividualized psychotherapy (routinely available in dialysis unit) 30–50 min 1× per wk for 12 wk; followed by as-needed psychologic care for 6 moBDI-II: after 3 mo, 14.1 (SD, 8.7) versus 21.2 (SD, 9.1); P=0.001; after 9 mo, 10.8 (SD, 8.8) versus 17.6 (SD, 11.2); P=0.002Suicide Risk Module (MINI): baseline 2.2 (SD, 5.1) versus 1.4 (SD, 3.5); P=0.23; after 3 mo, 1.2 (SD, 4.2) versus 0.7 (SD, 1.9); P=0.43; after 9 mo, 0.6 (SD, 1.2) versus 0.6 (SD, 2.0); P=0.95Fair
MINI: the mean change from baseline (SE) favored interventionOverall reduction, within-group comparison: significant reduction within T group (P=0.007) versus C (P=0.13)
After 3 mo: 4.5 (SE, 0.4) versus 2.1 (SE, 0.6); P<0.001QoL: CBT group significantly improved several dimensions of KDQOL. Between-groups significant improvement in burden of kidney disease, quality of social interaction, sleep, overall health, and mental component summary dimensions
After 9 mo: 4.4 (SE, 0.4) versus 2.9 (SE, 0.5); P=0.03
  Lerma et al. (41); 2017; 38 versus 22; Tx=5 wk, F/U=9 wkCBT: 5 group sessions (2 h), 1× per wk after HD sessionWaiting listEnd-of-treatment BDI-II, 10.2 (SD, 8.2) versus 15.0 (SD, 10.9); P=0.08Overall QoL (PLC): baseline, 99.4 (SD, 21.3) versus 91.5 (SD, 19.5); P=0.20Fair
Follow-up BDI-II: 7.1 (SD, 7.2) versus 14.7 (SD, 9.7); P=0.003After 5 wk, 109.6 (SD, 21.1) versus 94.0 (SD, 21.0); P=0.02
Within-group reduction in scores: P<0.001 versus P=0.87After 9 wk, 112.5 (SD, 23.8) versus 91.3 (SD, 22.5); P=0.004
RR of reducing depressive symptoms (between groups), 1.7Overall within-group P=0.001 versus P=0.663; Cohen d=0.93 (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); 2016; 30 versus 30; Tx=unclear, F/U=30 dTelenursing: 30-min telephone follow-up sessions 30 d after dialysis shiftTAUDASS-21 depression subscale after intervention (mean [SD]): 8.96 (1.17) versus 16.20 (1.60); P=0.05NAPoor
  Li et al. (42); 2020; 36 versus 36; Tx=6 mo, F/U=6 moHome nursing visits: care, guidance for patient and family, counseling, and dietary guidanceTelephone follow-up at 1, 3, and 6 mo after dischargeAfter intervention SDS: 36.48 (SD, 5.06) versus 48.80 (SD, 5.27); P<0.001QoL (KDQOL-36): both groups experienced significant improvement (P<0.001); scores in Tx group higher than C (P<0.001)Poor
Both groups experienced significant decline in scores (P<0.001)
  Liao et al. (43); 2020; 64 versus 64; Tx=unclear, during inpatient stay, F/U=3 moComprehensive nursing: health education 1–2× per wk; CBT; progressive relaxation, extended f/u careConventional careAfter intervention SDS: 51.02 (SD, 20.59) versus 60.06 (SD, 28.91); P=0.05QoL (KDQOL-36) at 3-mo f/u: greater improvements from baseline for physical activity, mental state, burden of kidney disease, symptoms of kidney disease, and effects of kidney disease in T compared with C (all P<0.05)Poor
Improvement in scores from baseline: 9.81 (SD, 19.32) versus 3.96 (SD, 10.79); P=0.04
 Acupressure
  Kalani et al. (39); 2019; 32 versus 32 versus 32; Tx=4 wk, F/U=4 wkAcupressure: applied during first 2 h of HD; 3× per wk for 4 wk; each session lasted 20 minSham: same as acupressure group except pressure applied 1 cm from acupressure pointsControl: TAUPost-test BDI-II: T 20.6 versus sham 25.5 versus C 24.9; significant difference T versus sham and C (P=0.001 for both); no difference between sham and C (P=0.22)NAFair
  Tsay et al. (48); 2014; 36 versus 36 versus 36; Tx=4 wk, F/U=4 wkAcupressure: applied for 15 min 3× per wk for 4 wkTEAS: applied for 15 min 3× per wk for 4 wkControl group (not described)Acupressure and TEAS are similarly effective, and significantly more effective than no intervention (P=0.009 and P=0.008, respectively); no difference between acupressure and TEAS (P=0.95)Fatigue (PFS): baseline T 5.92 (SD, 1.39) versus TEAS 5.60 (SD, 1.30) versus C 6.01 (SD, 1.60); follow-up T 4.61 (SD, 1.72) versus TEAS 4.70 (SD, 1.50) versus C 5.70 (SD, 1.80);post-hoc analysis found significantly lower levels in T (P=0.006) and TEAS (P=0.02) versus C. No difference between T and TEASPoor
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 (P=0.05) and TEAS (P=0.016); no difference between T and TEAS
 Exercise
  Frih et al. (34); 2017; 28 versus 22; Tx=4 mo, F/U=4 moExercise (endurance-resistance) training: 60 min, 4× per wk on nondialysis daysSedentary controls; no interventionFavors exercise: T HADS depression scores were not different than C before intervention, but significantly lower than C after intervention (P<0.01). Within-group decrease also significant for T, but not CSF-36 PCS: T significantly improved (P<0.01) from baseline; no difference for C; no difference between groups at either time pointPoor
Significant group × period interaction effect for HADS depression scores: F(1, 39)=43.91, P<0.001SF-36 MCS: T improved significantly, but not C; no difference before, but T significantly better than C after (P<0.01)
  Kouidi et al. (40); 2010; 25 versus 25; Tx=1 yr, F/U=1 yrET program (intradialytic): warm-up, cycling, strengthening, cooldown, 3× per wk, 60–90 min during first 2 h of HD sessionSedentary controlFavors ET in both BDI-II and HADS scores (P<0.001)Heart rate variability indices: Standard deviation of all RR intervals, mean square successive differences, 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<0.001Poor
 Other interventions
  Babamohamadi et al. (28); 2017; 30 versus 30; Tx=1 mo, F/U=1 moQuran: listen to audio of Quran recitation on headphones for 20 min, beginning 5 min before dialysisTAUPost-test BDI-II scores: 14.5 (SD, 4.8) versus 31.6 (SD, 9.2); P<0.001NAPoor
Significant between-subjects treatment effect, independent of age (F=9.3, P=0.004, Cohen d=0.85).
  Beizaee et al. (29); 2018; 40 versus 40; Tx=4 wk, F/U=4 wkGuided imagery: 3× per wk for 4 wk, in-person with psychologist; 30 mins before HD session; includes audio recording of nature soundsTAU, nearly silent environmentPost-test HADS scores: 10.02 (SD, 2.58) versus 11.65 (SD, 2.33)SBP: mean (SD) before, 129.22 (12.70) versus 132.85 (13.22); mean (SD) after, 121.75 (12.73) versus 134.87 (12.68)Fair
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; 35 versus 34; Tx=1 mo, F/U=1 moBenson relaxation technique: performed 20 min 2× per d for 1 moTAUOnly T group scores decreased; the difference between groups was significant (P=0.01)NAPoor
  Rahimipour et al. (45); 2015; 25 versus 25; Tx=8 wk, F/U=12 wkHope therapy: sessions using Schneider hope therapy theory, 1× per wk for 8 wk, 1–1.5 h during first 2 h of dialysisControl: listening session in which patients could talk about their disease and problems, 1× per wk for 8 wkImmediately after 8-wk intervention (t=12.75; P<0.001), and at 1-mo follow-up (t=13.83; P<0.001)NAPoor
  Thomas et al. (47); 2017; 21 versus 20; Tx=8 wk, F/U=8 wkMBSRa: guided, chairside meditative practices, 10–15 min, 3× per wk during hemodialysis sessionsTAUaChange in PHQ-9: −3.0 (SD, 3.9) versus 2.0 (SD, 4.7); P=0.45NAFair
  Widyaningrum and Djarwoto (51); 2013; 18 versus 18; Tx=3 wk, F/U=3 wkLPD relaxation technique and repetitive prayer practice, 2× per d for 21 dControl group (not described)Significantly decreased BDI-II scores within both groups, and greater in LPD, but between group difference NS (P=0.20)QoL (KDQOL-SF36): significantly greater change in sleep and overall health associated with LPD versus control; no other differences were significantPoor
  • 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; Δ, 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.

  • a Both treatment and control groups also received psychoeducational literature on anxiety and depression.