REVIEW

CURRENT
OPINION Depression in dialysis
Na Tian a, Na Chen a, and Philip Kam-Tao Li b

Purpose of review
The aim of this study was to examine updated prevalence rates, risk factors and the prognosis, diagnosis
and treatments for depression among dialysis patients.
Recent findings
Depression influences prognosis, complications, quality of life (QOL), treatment and costs for dialysis
patients worldwide. Reported prevalence of depression is 13.1–76.3%; it is higher for dialysis than
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transplant and higher post than predialysis. Reported depression rates with peritoneal dialysis (PD)
compared with in-centre haemodialysis (HD) are inconsistent. Related medical factors are known, but
suspected associated patient characteristics including gender and race remain unexplored. Associations
between depression in dialysis and QOL, mortality, pathophysiological mechanisms of increased mortality,
infection and pathways of inflammation-mediated and psychosocial factors require clarification. Several
depression screening instruments are validated for dialysis patients – the Structured Clinical Interview for
DSM disorders (SCID) remains the gold standard – but authors suggest the diagnostic standard should be
higher than for the general population. Short-term studies indicate nonpharmacological therapy achieves
clinical effects for depression in dialysis patients, but research on long-term effects is needed.
Summary
Depression management through early screening and continuous care models emphasizing dynamic
relationships between healthcare teams, patients and families should be encouraged. Large-scale studies of
short-term and long-term benefits of pharmacological and nonpharmacological depression management are
warranted.
Keywords
cognitive dysfunction, depression, dialysis, lifestyle, renal replacement therapy

INTRODUCTION Regional differences

Patients undergoing renal replacement therapy face Depressive disorder prevalence estimates are
qualitative lifestyle changes in addition to medical between 13.1 and 76.3% for patients on dialysis,
problems and socioeconomic pressures, and depres- much higher than for the general population. Most
sion is common in this population. The WHO-pre- studies employ single-centre surveys but include
dicted depression would be the second leading relatively large samples. Depression prevalence data
noncommunicable cause of disability of the global for dialysis patients vary by continent and within
population by 2020. Levy introduced ‘psychoneph- individual countries, partially due to differences in
rology’ to refer to patients’ psychiatric issues related sample sizes and assessment tools and lack of
to kidney disease, particularly those undergoing
maintenance dialysis or transplants [1]. Depression
has various impacts on prognoses, complications, a
Department of Nephrology, General Hospital of Ningxia Medical Univer-
quality of life (QOL), treatment effects and medical sity, Yinchuan, Ningxia and bDepartment of Medicine and Therapeutics,
costs. Although depression in dialysis is common Carol and Richard Yu Peritoneal Dialysis Research Centre, Prince of
and recently has been studied more widely, more Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong
Kong, SAR, China
treatment breakthroughs and standardized guide-
Correspondence to Philip Kam-Tao Li, Honorary Professor, Department
lines for diagnosis and treatment are needed.
of Medicine and Therapeutics, Carol and Richard Yu PD Research
Centre, Prince of Wales Hospital, Chinese University of Hong Kong,
30–32 Ngan Shing Street, Shatin, New Territories, Hong Kong. E-mail:
EPIDEMIOLOGY [email protected]
There are various approaches to the epidemiology Curr Opin Nephrol Hypertens 2021, 30:600–612
and treatment of depression for patients on dialysis. DOI:10.1097/MNH.0000000000000741

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 Depression in dialysis Tian et al.

cross-sectional design compared different patients

KEY POINTS in predialysis and HD group. As to haemodialysis vs.
 Reported prevalence of depression is 13.1–76.3%; it is transplantation, conclusions were relatively consis-
higher for dialysis than transplant and higher post tent on depression being more prevalent in a hae-
than predialysis. modialysis cohort than a transplant group [6,25],
which is mostly due to the significant improvement
 Several depression screening instruments are validated
of kidney-related symptoms, QOL and cumbersome
for dialysis patients – the Structured Clinical Interview
for DSM disorders (SCID) remains the gold standard – treatment after transplantation.
but the diagnostic standard for dialysis patients should Home PD and in-centre HD are the most com-
be higher than for the general population. monly used modalities in dialysis population. One
observational study comparing QOL and physical
 Short-term studies indicate nonpharmacological therapy
function of older patients (> 60 years) between
achieves clinical effects for depression in dialysis
patients, but research on long-term effects is needed. recipients of home-assisted PD and in-centre HD
found no difference in their odds of HADS, while
assisted PD was associated with higher treatment
satisfaction (P ¼ 0.04) compared with HD [26].
multivariate analysis to adjust for confounders (see Another well matched demographic group of older
representative data by continent in Table 1 [2– dialysis patients on PD vs. in-centre HD showed that
& & &
7,8 ,9,10 ,11–17,18 ,19–22] and reported preva- those on PD scored better on Short Form-12 Mental
lence of depression in dialysis populations by conti- and Physical Component Summary scales (SF-12
nent in Fig. 1. Table 2 compares the representative MCS) with significantly less possible depression
studies in different countries from the perspectives [27], strongly supporting offering PD to all suitable
of nation, research design, study population, sample older people. In recent years, assisted PD is becom-
size and diagnostic methods. It can be seen that in ing increasingly available as a model of care for older
addition to the differences of above factors, the patients in many countries involving the use of
underlying diseases, complications, economic sta- overnight cyclers (automated PD), which are set
tus, medical insurance, family support, drug factors up by family members or healthcare assistants
and so on may be contributing factors to the wide who visit once daily. This is more convenient for
variation of incidence rate of depression. Neverthe- patients and their families. In general, trials on the
less, depression prevalence among dialysis popula- relationship of prevalence of depression and dialysis
tions is considerably higher than for the general modality are sparse and specially warranted.
population, which was estimated to be 264 million
people – 3.38% of the world’s population – accord-
ing to a 2020 WHO report. RELATED RISK FACTORS

Variations in dialysis modality Medical factors

As peritoneal dialysis is less common, most of the Primary diseases such as diabetes, cardiovascular
research studies examine depression in haemodial- disease (CVD) [28], malnutrition [29] and their com-
ysis and transplant patients. Actually, many patients plications are closely related to depression. In addi-
experience anxiety or depression before the dialysis tion, neuropsychiatric symptoms and organ
stage and the reports on changes of depression status dysfunction due to end-stage kidney disease (ESKD)
after dialysis were inconsistent. Bezerra et al. [23] are often difficult to distinguish from depressive
reported decreased depression, anxiety and stress symptoms. The symptoms of inadequate dialysis
scores after patients start dialysis, both peritoneal and depression may overlap, so that patients who
dialysis (PD) and haemodialysis (HD) modality. are in fact depressed may be misdiagnosed as having
However, a cross-sectional survey from Pakistan inadequate dialysis and conversely, those who are
showed that significant depression risk was 2.26 diagnosed with depression may in fact be under-
times greater in HD patients than predialysis dialyzed and not depressed. This reminds us that we
patients after adjusting for variables [24]. Although should first control medical factors to make patients
both of these two studies used hospital anxiety and achieve dialysis adequacy. The Dialysis Outcomes
depression scale (HADS) to screen depression, study and Practice Patterns Study (DOPPS) reported
by Bezerra et al. [23] has excluded somatic symptoms reduced health-related QOL (HRQoL) scores in
to prevent bias from physical disorders. In addition, patients undergoing in-centre HD three times
study by Bezerra et al. [23] with a prospective cohort weekly [30], and Frequent Hemodialysis Network
design compared pre and after dialysis in the same trial patients randomized to in-centre short daily
study participants, while the Pakistan study with a HD six times/week experienced significant

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 602
Table 1. Prevalence of depression in patients from different continents undergoing dialysis

Publication Sample
First author Year Type of study size Prevalence Dialysis modality Country Depression Scale

NORTH AMERICA Feroze et al. [2] 2012 cross-sectional Study 170 36% haemodialysis and US Beck Depression Inventory
peritoneal dialysis
Lacson et al. [3] 2012 cohort study 6415 14.1% haemodialysis US Two items of SF-36
Haverkamp et al. [4] 2019 observational, prospective 513 44% haemodialysis US Beck Depression InventoryII
cohort study (BDI-II)
Sy et al. [5] 2019 cohort study 746 13.1% dialysis US CES-D scale
Dialysis and transplantation

patients
SOUTH AMERICA Brito et al. [6] 2019 cross-sectional study 130 41.7% dialysis patients Brazil Beck Depression Inventory
Stasiak et al. [7] 2014 observational cross- 155 29.6% haemodialysis Brazil BDI
sectional study 14.8% peritoneal dialysis HADS
&
ASIA Chan et al. [8 ] 2020 prospective observational 267 58.8% peritoneal dialysis (PD) China, Hong Kong Patient Health Questionnaire

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study patients. (PHQ-9)
Ibrahim et al. [9] 2013 cross-sectional study 274 21.1% 183 haemodialysis Malaysia Beck Depression Inventory-II
91 PD patient (BDI-II)
&
Lin et al. [10 ] 2020 prospective cohort study 275 31.3% PD China Beck Depression Inventory-II
(BDI-II)
Mosleh et al. [11] 2020 cross-sectional, single- 122 24.6% CKD and haemodialysis Saudi Arabia Hospital Anxiety and
centre study Depression Scale (HADS)
OCEANIA Bautovich et al. [12] 2018 observational study 45 13.3% haemodialysis Australia Beck Depression Inventory
(BDI) and Cognitive
Depression Index (CDI)
Kwan et al. [13] 2019 cross-sectional study 110 40.6% haemodialysis and Australia Hospital Anxiety and
peritoneal dialysis Depression Scale (HADS)
EUROPE Cirillo et al. [14] 2018 monocentric cross- 145 46% haemodialysis (HD) and Italy Patient Health
sectional study peritoneal dialysis (PD) Questionnaire-9 (PHQ-9)
population
Saglimbene et al. [15] 2017 prospective multinational 2278 46% haemodialysis Portugal, Turkey, Beck Depression Inventory
cohort study Italy and France (BDI) II questionnaire
Simic et al. [16] 2009 prospective follow-up 128 45.3% haemodialysis (HD) and Serbia Beck Depression Inventory-
study peritoneal dialysis (PD) BDI-II score
population
Riezebos et al. [17] 2010 a prospective, single- 101 41.6% haemodialysis and Netherlands Hospital Anxiety and
centre cohort study peritoneal dialysis Depression Scale (HADS)
&
Isik et al. [18 ] 2019 cross-sectional study 117 22.2% haemodialysis Turkey Beck Depression Inventory
Brekke et al. [19] 2013 observational study 237 29.5% haemodialysis and Norwegian Beck Depression

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peritoneal dialysis Inventory (BDI)
AFRICA Donia et al. [20] 2015 cross-sectional study from 76 76.3% haemodialysis Egypt Beck Depression Inventory II
single center
Ganu et al. [21] 2018 cross-sectional, two renal 106 45% haemodialysis Ghana Patient Health Questionnaire
dialysis units (PHQ-9)
Elkheir et al. [22] 2020 descriptive cross- 75 68% haemodialysis Sudan Diagnostic and Statistical
sectional, hospital- Manual of Mental
based study Disorders, Fourth Edition

Volume 30  Number 6  November 2021

(DSM-IV)
 Depression in dialysis Tian et al.

FIGURE 1. Prevalence rates of depression in dialysis population in different continents as reported in the literature.

improvement in physical-health composite scores patients, and sleep disorders (obstructive sleep
but not self-reported depression [31]. Further, apnoea, restless legs) and fatigue can be caused by
although FREEDOM, a prospective cohort study mea- or be the cause of clinical depressive symptoms [34].
suring the potential benefits of at-home short daily However, the causal relationship between sleep dis-
(six times/week) haemodialysis reported an associa- orders and depression remains controversial.
tion between long-term improvements in physical Other symptoms in CKD populations are also
&
and mental HRQoL [32], the Nocturnal Trial partic- associated with depression. Sukul et al. [35 ]
ipants’ mean BDI scores decreased with nocturnal HD reported that 3780 CKD patients in the USA, Brazil
(six times per week, n ¼ 45) and conventional HD and France who answered the pruritus question
(three times per week, n ¼ 42) (from 11.8 to 9.7 and demonstrated a high prevalence of pruritus in no-
11.7 to 11.1, respectively) after 12 months, with no dialysis CKD and strong associations of pruritus
significant difference in the change between groups with poor HRQoL, self-reported depression symp-
with covariate adjustment for age, diabetic status, toms and self-reported poor sleep. The prevalence
baseline level of the glomerular filtration rate and ratio of patient-reported depression was 1.8 times
&
the baseline variable under analysis and the interac- higher for moderate pruritus than no pruritus [36 ].
tions of these factors with time. [31]. Thus, frequent
haemodialysis may benefit patients’ physical and
mental wellbeing but cannot be considered a depres-
Nonmedical factors
sion treatment because economic evaluations and
side effect assessments are lacking. Sex
In addition, physical frailty, depression and cog- Epidemiological studies in general population show
nitive impairment are interlinked, and depression is that women experience more sleep problems and
sometimes difficult to discern from frailty in older depressive symptoms around times when sex hor-
adults. For example, Chinese PD patients’ nutri- mones change, such as puberty and menopause.
tional status and clinical outcomes were reportedly Many studies have compared depression incidence
adversely influenced by physical frailty and depres- rates between male and female dialysis patients. The
sive symptoms [33]. Meanwhile, a study reported odds of depression are 5.9 times higher for women
poor sleep quality for more than 70% of HD than for men in dialysis patients [27]. Sex has a

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Dialysis and transplantation

Table 2. Brief introduction of depression assessment scales commonly used in population on dialysis treatment

Assessment
tool Brief introduction Reference

DSM-V Criteria A–C represent a major depressive episode Smith et al. [68] 1985
Five (or more) of the following symptoms (nine items) have been present during the same
2-week period and represent a change from previous functioning: at least one of the
symptoms is either (1) depressed mood or (2) loss of interest or pleasure
The symptoms cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning
The episode is not attributable to the physiological effects of a substance or to another medical
condition
The occurrence of the major depressive episode is not better explained by schizoaffective
disorder, schizophrenia, schizophreniform disorder, delusional disorder or other specified
and unspecified schizophrenia spectrum and other psychotic disorders
There has never been a manic episode or a hypomanic episode
SCID-II Semistructured interview. The following 10 disorders were assessed: First et al. [69] 1997
major depressive disorder (MDD), alcohol use disorder (AUD), substance use disorder (SUD),
posttraumatic stress disorder (PTSD), panic disorder (PD), agoraphobia, social anxiety
disorder (SAD), specific phobia, obsessive–compulsive disorder (OCD) and generalized
anxiety disorder (GAD)
HADS The HADS scale consists of 14 questions, of which seven evaluate the level of depression Zigmond et al. [70] 1983
(questions 2, 4, 6, 8, 10, 12 and 14) and the other seven evaluate the anxiety level
(questions 1, 3, 5, 7, 9, 11 and 13) of the respondents. The range of the total score of
anxiety and depression level is between 0 and 21. Classification: 0–7 indicating no
anxiety or depression, score 8–10 indicating moderate levels of anxiety or depression,
and score> 11 indicates high levels of anxiety / depression.
BDI series The BDI contains 21 items, where each item is scored on a four-point scale of 0 to 3, with a Beck et al. [71] 1961
assessment form total score of 0 to 63. A total score of 9 points suggests no depression, 10–15 suggests
mild depression, 16–23 suggests moderate depression and24 suggests severe depression.
BDI-IA contains 21 items, graded from 0 to 3; total scores range from 0 to 63. Classification: Beck et al. [72] 1987
minimal range 0–9, mild depression10–16, moderate depression 17–29, and severe
depression 30–63.
BDI-II contains 21 items, graded from 0 to 3; total scores range from 0 to 63. Classification: Beck et al. [73] 1996
minimal range 0–13, mild depression 14–19, moderate depression 20 -28, and severe
depression 29-63.
BDI-FS contains seven items, graded from 0 to 3; total scores range from 0 to 21. Beck et al. [74] 2000.
Classification: minimal 0–3, mild depression 4–8, moderate depression 9–12, and severe
depression 13–21.
PHQ-9 PHQ-9 consists of nine questions corresponding to the nine criteria for defining depression Kroenke et al. [75] 2001
according to Diagnostic and Statistical Manual Fourth Edition (DSM-IV). Scale: A 4-point
scale indicates degree of severity; items are rated from 0 (not at all) to 3 (nearly every day),
total scores range from 0 to 27. Severity: 1–4 no depression, 5–9 mild depression, 10–14
moderate depression, 15–19 moderately severe depression, and 20–27 severe depression.
CESD It includes 20 items that survey mood, somatic complaints, interactions with others, and motor Radloff et al. [76] 1977
functioning. The final score spans from 0 to 60, a higher score reflects greater symptoms of
depression. A cut-off value of 16 is used to signify depression.
GDS GDS consists of 15 items, the range is 0 (no depression) to 15 (severe depression). The total Marc et al. [77] 2008
score is calculated by summing responses that endorse depression. Negatively endorsing
items 1, 5, 7, 11 and 13 indicates depression, while positively endorsing the remaining
10 items indicates depression. The developer’s website reports scores 5 are suggestive of
depression and those with 10 indicate highly likely depression.
SF-36 The SF36 includes the two questions-’Have you felt downhearted and blue?’ (i.e. ‘Blue’). and’ Lopes et al. [42] 2002
Have you felt so down in the dumps nothing could cheer you up?’ (i.e. ‘dumps’). Patients
rated each question, choosing a number between 1 and 6 to best describe their response.
A response of 6 means that the patient feels this way ‘none of the time’. A response of 3
means that patient feels this way ‘a good bit of the time’; a 2, ‘most of the time’; and a 1,
‘all of the time’. SF-36 response  3 on the two questions at issue were accepted as
suggesting the presence of depressive symptomatology.
BDI, Beck Depression Inventory; BDI-FS, Beck Depression Inventory-Fast Screen; BDI-IA, Beck Depression Inventory IA; BDI-II, Beck Depression Inventory-II; CESD,
Center for Epidemiological Study of Depression; DSM-V, Diagnostic and Statistical Manual of Mental Disorders V (DSM-V); GDS, Geriatric Depression Scale;
HADS, Hospital Anxiety and Depression Scale; PHQ-9, 9-item Patient Health Questionnaire; SCID, Structured Clinical Interview for DSM disorders (SCID); SF-36,
Short Form – 36.

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 Depression in dialysis Tian et al.

certain impact on the relationship between depres- Malaysia found that dialysis patients having religion
sion and mortality in the general population. One was associated with lower depression scores [44]. A
general population-based survey in north-east of positive correlation between hope and religious
France, including 6043 individuals (2892 men) dem- beliefs was found in patients undergoing haemo-
onstrated that depressive mood is significantly asso- dialysis; in that study, 97% of patients attributed
&
ciated with cardiovascular mortality in men [hazard their hope to religious beliefs [45 ].
ratio ¼ 1.63; 95% confidence interval (95% CI):
1.00–2.65] and cancer mortality in women (hazard Family
ratio ¼ 1.71; 95% CI: 1.11–2.64) [37]. A study of The influence of family factors on depression is
patients waiting for organ transplants, with over bidirectional. Family support can partially reduce
83% of whom were kidney failure patients on dialy- patients’ psychological pressure and enhance phys-
sis, reported that women had more negative ical QOL; appraisal support mediates the relation-
thoughts than males (social isolation, 18.5 vs. ship between sleep disturbances and depressive
11.5%; ideas of impending death, 23.1 vs. 14.2%; symptoms [34]. However, family burdens related
suicidal thoughts, 8.3 vs. 5.3%, respectively) [38]. to a spouse [43] and number of children [29] are
However, a systematic review has analysed 13 stud- also risk factors for depression.
ies that investigated the relationship between sex
hormones, sleep and depression. It was unclear what Lifestyle change
effect sex hormones had on sleep problems and All dialysis modalities indicate major disruptions in
depression [39]. Sex role aspects are also reflected lifestyle due to treatment regimens (dialysis sched-
in endocrine stress reactions and possibly influence ules, ancillary treatments and hospitalizations).
associated neuropsychological processes. Patients also fear disability, morbidity and a short-
ened lifespan. HD groups reported less medication
Race adherence than transplant groups [25] and signifi-
Table 1 lists depression prevalence in different global cantly less adherence among individuals likely to be
areas, which may entail racial or ethnic differences. clinically depressed (BDI 3 15). Nonadherence in
Early studies showed no difference between African– dialysis patients was associated with increased
Americans and whites in dialysis populations [40,41]. depression and mortality [46], and other studies
A small sample of HD patients from the USA in strongly suggest that depressive affect is a primary
African–Americans vs. whites showed no significant contributor to low medication adherence in patients
difference in the reported BDI Scores (11.2 vs. 10.9, with ESKD or haemodialysis or kidney transplant
P ¼ 0.6) or Cognitive Depression Index (CDI) scores recipients [25,46].
(6.0 vs. 6.0, P ¼ 0.9) [34]. However, in exploratory
analyses, spiritual and religious beliefs appear to be of
greater importance to African–Americans [41]. Ran- ASSOCIATIONS BETWEEN DEPRESSION
domly selected HD patients from the DOPPS study in AND PROGNOSIS
the USA (2855 patients) vs. five European countries Several associations have been identified between
(2401 patients) showed that depression was statisti- prognosis and patient depression.
cally significantly associated with being white [42].
The interaction between racial and ethnic character-
istics of patients on maintenance dialysis with Mortality
depression and anxiety needs to be studied more The Reasons for Geographic and Racial Differences
extensively to assess better approaches to healthcare in Stroke (REGARDS) study showed a significant
for these individuals. correlation between time-varying depressive symp-
toms and increased risk of all-cause mortality, CVD
Socioeconomic factors and non-CVD death in the general population [47].
Studies from Asia reported higher frequencies of Dialysis is often accompanied by various complica-
depression in patients with ESRD in urban than in tions, such as diabetes, which also has a high inci-
rural areas [24]. Low income [43], unemployment dence of depression and is independently associated
[2] and low education levels [29] are risk factors for with all-cause mortality [48]. Farhat et al. [49] con-
depression of CKD or dialysis patients. However, in ducted a meta-analysis to detect the relationship
the reportings of prevalence of depression, adjust- between depression and death from the perspectives
ment of socioeconomic factors is usually not made. of depression symptoms and diagnosis. In the 12
These factors should be considered in future studies included studies, depressive symptoms significantly
for comparison across different groups. A study from increased death risk (þ51%). In the nine that

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Dialysis and transplantation

reported depression scores, the unadjusted hazard reduce involvement in social, occupational and rec-
ratio for depressive scores showed a significant reational activities [59], resulting in considerably
increase in mortality per unit of change; when reduced QOL [58]. Depression is associated with
combined with six reports of corrected hazard ratio, poor QOL for patients with progressive CKD [60]
depressive scores were significantly associated with and those on haemodialysis [61]. QOL impairment
mortality (adjusted hazard ratio, 1.04; 95% CI: 1.01– is reportedly a crucial predictor of prognosis in older
1.06). Larger studies also identified an independent patients on HD and may have more prognostic value
&
association between depression and mortality than depression [62 ]. Nevertheless, depression and
[17,50,51]. In studies examining physician-diag- reduced QOL are closely related.
nosed depression [42,52], there were significant
links between depression and mortality in univari-
ate and multivariate analysis. Strong evidence of the Other outcomes
close association between depression in dialysis and High depressive symptoms increased the risk of first
mortality had been previously reported, but causal- hospitalization (hazard ratio, 1.59; 95% CI: 1.03–2.47)
ity has only recently been identified. for in-centre HD patients [60]. A cohort study of 275
Inflammation is another pathophysiological CAPD patients found that the long-term technique
mechanism of increased depression-related mortal- survival was significantly reduced in the depressive
ity. In animal models, both stress and administra- group compared with the nondepressive group after
&
tion of epinephrine elevate plasma IL-6, consistent adjustment for confounders [10 ].
with evidence that IL-6 production is stimulated
through b-adrenergic receptors, among other path-
ways [53]. Thus, production of IL-6 and other proin-
Screening and diagnosis
flammatory cytokines can be directly stimulated by
negative emotions and stressful experiences, provid- Screening methods
ing a direct pathway [54]. In addition, depression The Structured Clinical Interview for DSM disorders
can down-regulate the cellular immune response, (SCID) remains the gold standard for definitively
consequently promoting processes that fuel diagnosing major depressive disorder in dialysis
sustained 7proinflammatory cytokine production patients [63]. The Beck Depression Inventory
like prolonged infection and delayed wound healing (BDI), the most used depression assessment, has
[54]. been widely validated for screening patients with
ESKD [41,64]. First used by Beck in 1961, the BDI was
revised in 1987, 1996 and 2000. The latest is the fast-
Infection screen version (BDI-FS), with fewer items (seven
A survey from Taiwan identified increased risks of rather than 21); grading remains 0–3, expediting
severe infections (þ14%; primarily sepsis and pneu- the questionnaire process without reducing diag-
monia) and fatal infections (þ22%) in dialysis (HD nostic value. Self-reporting scales may lead to over-
and PD) patients with previous depression diagnoses diagnosis by assigning symptoms commonly
[55]. Studies from the USA [56] and Asia [57] sug- experienced in ESKD (such as fatigue, sleep distur-
gested patients on peritoneal dialysis treatment with bance and poor appetite) as indicative of the somatic
depression had increased risks of peritonitis. Mech- symptoms of depression [65]. Competing factors of
anisms of the association between depression and high symptom burden, intercurrent events (CVD,
infection risk are not clear, but biological pathways infection, hospitalization for any reason) and kid-
such as inflammation-mediated and psychosocial ney disease related losses do add to the complexity
pathways such as attitude to disease are speculated. of identifying a pure depression.
Liu et al. [44] used the Short-Form Depression,
Anxiety and Stress Scale (DASS21) to measure the
Quality of life psychological states of HD or PD individuals, find-
QOL measures can be subjective or objective. Kim- ing it corresponds closely to the DSM-IV symptom
mel and Patel [58] have suggested that factors such criteria for generalized anxiety disorder (GAD). The
as age, ethnic or national background, stage of CKD, Hospital Anxiety and Depression Scale has been
modality of dialytic therapy, exercise interventions, validated in the general population. However, some
sleep disturbances, pain, erectile dysfunction, believe it is not effective for anxiety disorder screen-
patient satisfaction with care, depressive affect, ing in patients on dialysis [66]. Chilcot et al. [67]
symptom burden and perception of intrusiveness validated the Patient Health Questionnaire Anxiety
of illness may be associated with differential QOL and Depression Scale (PHQ-ADS) factor structure, a
perceptions. Patients with depression significantly composite measure of depression and anxiety using

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 Depression in dialysis Tian et al.

the Patient Health Questionnaire-9 and Generalized still investigative research and not yet into clinical
Anxiety Disorder Scale (GAD-7) in a 182-case sample applications yet.
of haemodialysis patients. They concluded that it
has good structural validity with haemodialysis
patients and sufficient uni-dimensionality to war- TREATMENT
rant using the total distress score. The depression Depression treatments for dialysis patients can be
assessment scales commonly used for patients on classified as pharmacological or nonpharmacological.
dialysis treatment are summarized in Table 2
[42,68–77]. Generally speaking, depression screen-
ing tools were developed in general populations and Pharmacological intervention
were not designed to identify the cause of symp- There are few high-quality studies on the effective-
toms. The gold standard diagnostic method is not ness and safety of antidepressant medication in
accessible in most nonmental health clinical envi- adults with ESKD on dialysis. The proportion of
ronments, wherein simple and quick self or clini- kidney failure patients on drug treatment for depres-
cian-administered depression screening tools are sion is lower than that of the overall population [28],
often used. Currently, the BDI, Patient Health Ques- and approximately 50% of those patients take insuf-
tionnaire (PHQ-9), Hospital Anxiety and Depression ficient dosage [78]. Depression treatments’ benefits
Scale (HADS) and Center for Epidemiologic Studies and side effects may differ for dialysis patients com-
Depression Scale (CSED) are all validated and most pared with the general population due to altered
commonly used questionnaires. clearances of antidepressant medication and the
severity of somatic symptoms of ESKD.
Diagnostic criteria Selective serotonin reuptake inhibitors (SSRIs)
In patients with ESKD, the symptoms of depression are currently the most popular medications for treat-
may be like those occurring with kidney failure or ing depression. In the general population, they
uraemia per se. Therefore, depression and anxiety effectively treat depression and obsessive-compul-
diagnosis and treatment are often delayed or missed sive disorder with a high degree of safety and few
with these patients. Over 70% of patients on main- side effects, toxic effects on the heart and sedative
tenance haemodialysis with symptoms of depres- effects. However, for patients with CKD, the clinical
sion or anxiety and described barriers to mental benefits are still under discussion. In the CAST
health treatment reportedly did not recognize their 12-week randomized clinical trial, 201 patients with
symptoms or perceive a need for therapy for their nondialysis-dependent CKD and moderate/severe
mental health. Considering the baseline kidney dis- depressive symptoms, treatment with sertraline
ease, some scholars suggest that the diagnostic stan- compared with placebo did not significantly
dard of depression in dialysis patients should be improve depressive symptoms [82]. Another ran-
higher than for the general population [78,79]. Pre- domized study of sertraline vs. placebo with 30
viously, the diagnosis of depression in dialysis patients with major depressive disorder undergoing
patients was based on a patient’s self-administered haemodialysis showed no benefits; depression
depression questionnaire score. Standard DSM-IV scores improved in both the treatment and control
criteria are accepted as a diagnostic standard, defin- groups [83]. The authors concluded that the small
ing a clinical syndrome as lasting for at least 2 weeks, sample size and the substantial dropout rendered
during which the patient experiences depressed benefit consideration inconclusive. However, sec-
mood or anhedonia as well as at least five DSM-IV ondary analyses of the CAST data showed that
symptom domains [80]. Some other questionnaires, patients with higher baseline high-sensitive C-reac-
such as the Patient Health Questionnaire and the tive protein may be more likely to benefit from
&& &&
Center for Epidemiological Studies Depression sertraline initiation [84 ]. Mehrotra et al. [85 ]
Scale (CES-D), have emphasized the reporting of conducted a multicentre comparison of cognitive
many depressive symptoms by patients with CKD. behavioural therapy (CBT) to sertraline for efficacy
Thus, rating scales may overestimate depression in with haemodialysis patients from the USA multi-
CKD patients [81]. Currently, existing diagnostic centres; sertraline treatment resulted in lower Quick
tools are mainly subjective scales with few objective Inventory of Depressive Symptoms-Clinician-Rated
indicators. Researchers have tried to look for objec- (QIDS-C) depression scores at 12 weeks [effect esti-
tive methods to focus on known physical cues mate, -1.84 (CI, -3.54 to -0.13); P ¼ 0.035].
(biomarkers) that correlate with depression, such Overall, for patients on chronic dialysis, well
as stress levels, head movements, psychomotor powered, placebo-controlled data are lacking. Two
symptoms and facial expressions and also affective small, randomized trials compared sertraline to
computing and social signal processing. These are placebo. The study by Taraz et al. [86] employed

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 608
Table 3. Studies on nonpharmacological treatment in recent years

Study
Ref. population Types of therapy Specific methods
Follow-up time Conclusion
&&
Zegarow et al. [92 ] haemodialysis Cognitive- In total, four studies were included in the meta-analysis; 5 weeks to The use of psychological intervention
(meta-analysis) patients behavioural 226 patients were included, of whom 123 underwent 3 months based on cognitive-behavioural
therapy (CBT) psychological intervention based on the assumptions of therapy significantly reduces the
cognitive-behavioural therapy. level of depression among
haemodialyzed patients.
Dialysis and transplantation

Griva et al. [93] haemodialysis brief self- The experimental group received haemodialysis and self- 12 months HED-SMART intervention, despite
management management intervention. focusing primarily on behaviour
intervention change, yielded significant
benefits by reducing symptoms of
depression for both the low stable

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and high stable groups.
Rahimi et al. [94] haemodialysis eye movement The EMDR intervention was carried out in a private and 4 weeks The patients’ level of depression
patients desensitization quiet room for 30–45 min in each session by the primary period significantly reduced in the
(EMDR) investigator. During haemodialysis, three times a week intervention group.
over 2 weeks.
Bargiel et al. [95] dialysis patients psychological Experimental group 1 was subjected to cognitive 4 weeks Only the use of the expanded
intervention intervention, who listened to a psychological intervention version of the psychological
recorded on a CD twice a day for 4 weeks. The intervention (cognitive/narrative)
recording included background music and therapeutic resulted in a decrease in the level
metaphors based on the principles of cognitive and of depression.
Ericksonian therapy.
Experimental group 2 was subjected to cognitive/narrative
intervention, who listened to a CD with a recorded
intervention twice a day for 4 weeks. In addition, the
group 2 met a psychologist twice a week within those 4
weeks. Meetings lasted approximately an hour, and each
of them was dedicated to a different subject.
Kargar et al. [96] Haemodialysis Nurse-led telephone Intervention group received telephone follow-up 30 days 30 days Tele-nursing programme was
patients follow ups (Tele- after dialysis shift, in addition to conventional treatment. associated with lower depression,
nursing) Every session lasted 30 min, as possible. anxiety and stress in intervention
vs. control group.
Hagemann et al. [97] haemodialysis music therapy After the initial evaluations, the music therapy sessions 4 weeks The results of this study indicate that
patients commenced. Eight sessions of music therapy were music therapy has a beneficial

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conducted with two weekly sessions and an average effect in reducing depressive
duration of 75 min per session. The music therapy sessions symptoms and improving the QOL
were conducted by the music therapist researcher herself, of the studied population.
always during the first half of the HD session
Bahmani et al. [98] haemodialysis patients cognitive existential The experimental group received a combination of 6 weeks Cognitive-existential group therapy
group therapy treatment including some elements of ‘existentialism’ significantly changed the level of
philosophy and a ‘cognitive’ approach. The treatment depression and hope of the
protocol lasted for 12 sessions of 90 min twice per week patients who were women treated

Volume 30  Number 6  November 2021

session. by dialysis.
 Depression in dialysis Tian et al.

50 patients on haemodialysis with depression taking

depressive symptoms compared to

anxiety and depression in patients

barriers and depressive symptoms

intervention directed at reducing
Laughter therapy can decrease the
number of dialysis patients with
sertraline 100 mg/day for 12 weeks; Friedli et al. [83]

while improving overall health-

patients allows for an effective
Guided imagery could reduce
included 30 HD patients using 50–100 mg/day of

PST provided to older dialysis

undergoing haemodialysis
sertraline, as tolerated, for 6 months. The results

related quality of life.

showed significant decreases in depressive symp-
toms from baseline in both the SSRI and placebo

a control group
groups but were underpowered to detect any benefit
of sertraline over placebo. These studies suggest that
Conclusion

placebo-treated individuals with ESKD demonstrate

a decrease in depressive symptoms over time that
parallels improvements in those treated with SSRIs,
but any potential benefits of these treatments have
Follow-up time

&&
not been robustly investigated [87 ].
A large retrospective analysis found that hae-
4 weeks

8 weeks

6 weeks

modialysis patients who initiated SSRIs with higher

QT-prolonging potential (citalopram, escitalo-
pram) had a significantly increased risk of sudden
cardiac death [adjusted hazard ratio 1.18 (95% CI:
The experimental group received Problem-Solving Therapy

1.05–1.31)] compared with those with lower QT-

The intervention group received a once weekly, 30-min
alongside their routine care, assisted by a certified

prolonging potential (fluoxetine, fluvoxamine,

intervention three times per week over four weeks,
The intervention group received the guided imagery

&
paroxetine, sertraline) [88]. Chilcot et al. [89 ] rean-
group laughter therapy session for 8 weeks.

alysed the survival data of a large sample of

haemodialysis patients (n ¼ 707), finding that anti-
depressant use was significantly associated with
mortality, increasing the hazard of death two-fold
when controlling for depression severity (PHQ-9).
A meta-analysis revealed that the benefits from the
SSRIs fluoxetine, sertraline, citalopram and escita-
lopram had generally very low or ungradable evi-
Specific methods

dence compared with placebos; antidepressant

psychologist.

therapy had no evidence of QOL benefit and uncer-

tain effects on risks for hypotension, headache,
(PST).

sexual dysfunction and increased nausea [90].

No study reported hospitalization, suicide or
attempted suicide, withdrawal from dialysis or
nonadherence to the recommended dialysis treat-
Types of therapy

ment as study endpoints. Although the data from

Guided imagery

laughter therapy

Problem-Solving

current evidence do not provide a guidance on the

Therapy

timing, dose, long-term benefit and safety of phar-

macologic treatment, it is reasonable to initiate a
cautious trial of a short course of antidepression
drugs while closely monitoring for depressive
symptom improvement and adverse effects.
Drug dosages also affect their therapeutic ben-
dialysis patients
haemodialysis

haemodialysis

efit. Benzodiazepines (e.g. diazepam) have been

population

used for acute episodes of panic and anxiety. Tri-

cyclic antidepressants and monoamine oxidase
Study

inhibitors are other treatment options but have

higher side effect profiles that limit their use.
Table 3 (Continued)

Tricyclic antidepressants should be used cautiously

Bennett et al. [100 ]
&
Beizaee et al. [99]

due to the risks of long QT syndrome and torsade de

Erdley et al. [101]

pointes, particularly when combined with antihist-

amines, antiarrhythmics and macrolides. Tricyclic
antidepressants do not require dose adjustment for
glomerular filtration rate, as they are metabolized
Ref.

in the liver. However, midazolam dosing should be

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Dialysis and transplantation

adjusted cautiously because the conjugate of its Financial support and sponsorship
main metabolite (alpha-hydroxy midazolam) causes None.
prolonged sedation in patients with kidney failure.
Commonly used antidepressants, dosage adjust- Conflicts of interest
ments and class side effects are summarized in the P.K.T.L. received speaker honorarium from FibroGen,
previous literature review [65]. AstraZeneca and Baxter.

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selective serotonin reuptake inhibitors among individuals receiving mainte- everywhere. Nephrol Dial Transplant 2021; 36:197–201.
nance hemodialysis. J Am Soc Nephrol 2019; 30:611–623. Patients with kidney disease and their care-partners should feel supported to live
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& patients is associated with increased mortality independent of concurrent pandemics. In the overall wellness programme for kidney disease patients, the
depression severity. Clin Kidney J 2020; 13:1109–1110. need for prevention should be reiterated. Early detection with prolonged course of
This study suggests that the association between antidepressant use and mortality in wellness despite kidney disease, after effective secondary and tertiary prevention
haemodialysis patients may well be independent of concurrent depression severity. programmes, should be promoted.

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