Treatment of Depression and Effect ofAntidepression Treatment on Nutritional Statusin Chronic Hemodialysis Patients
JA-RYONG KOO, MD; JONG-YOO YOON, MD; MIN-HA JOO, MD; HYUNG-SEOK LEE, MD;JI-EUN OH, MD; SEONG-GYUN KIM, MD; JANG-WON SEO, MD; YOUNG-KI LEE, MD;HYUNG-JIK KIM, MD;JUNG-WOO NOH, MD; SANG-KYU LEE, MD; BONG-KI SON, MD
: Depression, which is the most
malized protein catabolic rate, serum albumin and
common psychological complication in patients with
blood urea nitrogen level. Results
: All patients success-
end-stage renal disease (ESRD), has an impact on the
fully completed 8 weeks of antidepression treatment.
clinical outcome and is associated with malnutrition in
Antidepression treatment decreased the severity of de-
chronic hemodialysis patients. This study evaluated the
pressive symptoms (Hamilton Depression Rating Scale
effect of antidepression treatment on nutritional status in
score: 16.6 Ϯ 7.0 versus 15.1 Ϯ 6.6, P
Ͻ 0.01) and
depressed chronic hemodialysis patients. Methods
increased normalized protein catabolic rate (1.04 Ϯ
ty-two ESRD patients who underwent dialysis for more
0.24 versus 1.17 Ϯ 0.29 g/kg/day, P
Ͻ 0.05), serum
than 6 months were interviewed and completed a Beck
albumin (37.3 Ϯ 2.0 versus 38.7 Ϯ 3.2 g/l, P
Depression Inventory assessment. Thirty-four patients
and prehemodialysis blood urea nitrogen level (24.3 Ϯ
who had scores greater than 18 on the Beck Depression
5.6 versus 30.2 Ϯ 7.9 mmol/L, P
Ͻ 0.001). In the control
Inventory score and met Diagnostic and Statistical Man-
group, no change was noted during the study period.
ual of Mental Disorders, 4th Edition criteria for major
: This study suggests that antidepressant
depressive disorder were selected to receive paroxetine
medication with supportive psychotherapy can success-
10 mg/day and psychotherapy for 8 weeks. The remain-
fully treat depression and improve nutritional status in
ing 28 patients were assigned to the control group.
chronic hemodialysis patients with depression.
Change in the severity of depressive symptoms was
Antidepressant; Depression; Hemo-
ascertained by administering the Hamilton Depression
dialysis; Malnutrition; Nutrition; ESRD. [Am J Med Sci
Rating Scale. Nutritional status was evaluated by nor-
epression is the most commonly encountered depression in chronic dialysis patients presents
psychological complication of chronic dialysis
challenging problems.9 Antidepression treatment in
patients.1,2 Its prevalence varies widely across stud-
hemodialysis patients is complicated by difficulty in
ies, which may reflect the different criteria and
determining the impact of chronic disease on the
methodology utilized to diagnose depression.2,3 De-
symptoms and the patient’s response to antidepres-
pression has been shown to be associated with ex-
sant medication. The pharmacokinetics and safety
cess mortality in a variety of medical conditions.4,5
of antidepressants also have not been extensively
Studies on maintenance dialysis patients have also
documented in hemodialysis patients.
showed a significant association of depression with
Depending in part on the method used and the
mortality.6–8 However, the effective treatment of
population studied, 40% to 70% of patients with end-stage renal disease (ESRD) are malnourished,10,11 acomplication that appears to be associated with in-
From the Division of Nephrology, Department of Internal Med-
creased mortality.12 In our earlier study,13 we showed
icine (J-RK, J-YY, M-HJ, H-SL, J-EO, S-GK, J-WS, Y-KL, H-JK, J-WN) and
that depression is closely related to nutritional status
Department of Psychiatry (S-KL, B-KS), College of Medicine, Hal-
and could be an independent risk factor for malnutri-
lym University, Chunchon, Kangwon Do, South Korea.
tion, which could partially explain the causal relation
Submitted March 8, 2004; accepted July 24, 2004.
This work was supported by a research grant from Hallym
between depression and increased mortality in chronic
University, Chunchon, South Korea.
Correspondence: Ja-Ryong Koo, MD, Division of Nephrology,
The present study was undertaken to examine
Department of Internal Medicine, Chunchon Sacred Heart Hospi-
the feasibility of treating hemodialysis patients
tal, Hallym University, Kyo-Dong, Chunchon, Kangwon Do, 200-704, South Korea (E-mail address: firstname.lastname@example.org).
for depression and then to evaluate the effect of
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Antidepression Treatment and Malnutrition in Hemodialysis Patients
antidepression treatment on nutritional status in
calculator (Hypertension Dialysis Clinical Nephrology, http://
a subgroup of patients who were diagnosed with
www.hdcn.com/).16 The contribution of residual renal functionwas included in the calculation. Urea, albumin, hematocrit, and
bicarbonate were measured by standard techniques. Sampleswere taken with the subject in a nonfasting state and were
collected immediately after initiation of hemodialysis.
Multifrequency Segmental Bioimpedance Analysis
Our previous study13 investigated the relationship between
It is possible by multifrequency segmental bioimpedance anal-
depression and nutritional status in 76 ESRD patients who un-
ysis (BIA) to distinguish total body water and extracellular fluid
derwent dialysis for more than 6 months at the outpatient hemo-
(ECF) by using the resistance of cell membranes to relatively
dialysis unit of Hallym University Hospital (Chunchon, South
low-frequency currents.17 At high frequencies, currents flow
Korea). The patient characteristics, study design, measure of
across both intra- and extracellular spaces, but at low frequen-
depression, and nutritional status have been published.13
cies, currents flow mainly through extracellular space, allowing
Among 62 patients who completed our previous study, 34 pa-
the assessment of ECF alone. Segmental BIA can measure the
tients with depression who had a score greater than 18 on the
resistance of the trunk or each limb separately. The results of
Beck Depression Inventory (BDI) assessment and met the criteria
segmental BIA of the trunk and extremity are then summed up to
of the Diagnostic and Statistical Manual of Mental Disorders, 4th
produce whole-body BIA. It is a more appropriate approach to
Edition (DSM-IV) for major depressive disorder were assigned to
monitor body water during hemodialysis than whole-body BIA,
the treatment group and received the selective serotonin re-
because changes in local resistance can be allocated to segments
uptake inhibitor paroxetine at 10 mg/day and supportive psycho-
with uniform geometry and resistivity.18 Water volumes are cal-
therapy conducted by independent psychiatrists for a total of 8
culated by means of a population-based regression equation using
weeks. Patients were contacted every dialysis session during the
impedance index (height squared/resistance). Lean body mass
treatment period to ascertain whether they had taken the anti-
that contains 73.4% of total body water is determined and fat
depressant medication and to discuss possible side effects of
mass can be calculated by subtracting lean body mass from body
paroxetine. Individual supportive psychotherapy and psycholog-
ical counseling were done at intervals of 2 weeks. Group therapy
Eight stainless steel tactile electrodes were used to measure
was also done twice, at the start of treatment and after 4 weeks
the impedance of the trunk and extremity (Inbody 2.0, Biospace
of treatment. The study was terminated after 8 weeks, but pa-
Co, Seoul, South Korea), as in another study.19 The hand elec-
tients willing to continue treatment were offered follow-up care
trode consisted of thumb pipe and palm cylinder electrodes, and
by a psychiatrist. The remaining 28 patients without depression
the foot electrode consisted of frontal and rear sole plate elec-
were assigned to the control group of patients who received
trodes. Impedance was measured at frequencies of 5, 50, 250, and
neither medication nor psychotherapy. During the course of this
500 kHz. The validation of the method has been reported using a
study, dry weight, hemodialysis session length, and dialyzer were
sodium bromide dilution and a deuterium oxide dilution.17 The
not changed. The study protocol was approved by the Hallym
water volume in the trunk measured by BIA was compared with
University Hospital Institutional Review Board, and all patients
the water volume measured by dual energy x-ray absorptiometry
as the reference in 171 healthy subjects, giving a correlationcoefficient of 0.982 and a standard error of estimation of 0.695 L.
The measurements were performed at 30 minutes after hemodi-alysis with the subject in standing position. BIA was done repeat-
In the treatment group, changes in the severity of depression
edly before and after antidepression treatment.
before and after treatment were ascertained by administering theHamilton Depression Rating Scale (HDRS) and Zung Self Rating
Depression Scale (SDS) assessments. In this longitudinal study,we did not use the BDI questionnaire because some patients were
Data analysis was performed using a statistical software pro-
reluctant to fill out the same BDI questionnaire that was admin-
gram (SPSS for Windows, version 10.0; SPSS, Chicago, IL). Data
istered in the previous cross-sectional study.
are presented as mean Ϯ standard abbreviation (SD). Differences
The HDRS is a 17-item scale that evaluates depressed mood,
between groups were assessed by unpaired Student t
test and 2
vegetative and cognitive symptoms of depression, and comorbid
test. To compare values obtained at baseline and 8 weeks of
treatment, a paired t
test was used. P
values less than 0.05 were
symptoms of depression, with the exceptions of hypersomnia,
increased appetite, and concentration/indecision. The 17 itemsare rated on either a five-point (0 – 4) or a three-point (0 –2) scale.
The total score ranges from 0 to 53 with normal (0 – 6), mild(7–17), moderate (18 –24), and severe (25–53) depression. A psy-
The principal clinical data of the subjects are
chiatrist who was not an investigator determined the HDRS
presented in Table 1. In the treatment group, mean
age and proportion of diabetic patients were higher
The SDS is a 20-question self-rating assessment for depression
that is much simpler than the BDI questionnaire.15 The 20 items
than in the control group. Table 2 shows the baseline
are answered on a four-point Likert scale with 1 representing a
characteristics and the changes in the severity of
minimal (none or only a little of the time) and 4 a severe (most or
depression, nutritional parameters, BIA, and other
all of the time) problem. The raw score is converted to a 100-point
clinical variables in the treatment and control
scale, and the total score ranges from 35 to 100, with normal(35– 49), mild (50 –59), moderate (60 – 69), and severe (70 –100)
groups. Antidepression treatment decreased HDRS
score and increased nPCR, serum albumin, andblood urea nitrogen concentration. Antidepression
Dialysis Adequacy and Biochemical Analyses
treatment also induced a slight but significant in-
crease in intracellular fluid (ICF) volume and a
clearance, mL/minute; T, hemodialysis session length, minute;
decrease in ECF volume as measured by BIA. There
and V, volume of urea distribution, mL) and normalized proteincatabolic rate (nPCR) as a marker of protein intake were calcu-
lated with a web-based variable-volume, single-pool urea kinetic
bonate, hematocrit, and interdialytic weight gain
January 2005 Volume 329 Number 1
Baseline Clinical Characteristics in the Treatment
of depressed patients (16%) were being treated for
depression. Wuerth et al9 reported that depressionis treatable with antidepressant medication in a
small but significant percentage of ESRD patients
on chronic peritoneal dialysis. In their study, 45%
(27 of 65) of the eligible patients with depression
agreed to further assessment with possible treat-
ment and 11 of 20 patients for whom antidepressant
medication was prescribed completed 12 weeks of
therapy. Treatment of depression is dictated by thepatient’s needs and acceptance for medication and
BDI, Beck Depression Inventory. Values are expressed as mean
psychiatric referral, as well as the nephrologist’s
comfort with prescribing antidepressants. In our
study, all of the eligible and enrolled patients com-pleted the antidepression treatment trial withoutdropout. Reasons may be ease of administration (one
during antidepression treatment. In the control
tablet per day), lack of side effects, combined psy-
group, no change was noted during the course of this
chosocial support, and nursing staff’s effort to in-
crease medication compliance. There may be also
All patients successfully completed 8 weeks of
supportive psychotherapy and antidepressant med-
cultural and racial differences in patients’ responses
ication. Paroxetine was well tolerated by study pa-
to medical recommendation. Because most of the
tients without evidence of major adverse events,
patients enrolled in this study reside in a rural area,
even though four patients (8.3%) had mild central
patients’ characteristics and response to medical
nervous symptoms (drowsiness, dizziness) during
recommendation could be different from those of
patients who undergo dialysis in urban hemodialy-sis units located in large cities.
Our earlier cross-sectional study13 showed posi-
tive correlations between the severity of depressive
There is a paucity of data relating to the effective-
symptoms and the degree of malnutrition in chronic
ness of therapeutic interventions in the treatment of
hemodialysis patients. In this prospective study, an-
depression occurring in patients with ESRD.20,21 A
tidepression treatment increased nPCR, blood urea
recent study22 showed that only a small percentage
nitrogen, and serum albumin concentrations, all of
Baseline Values and Changes in the Severity of Depression, Nutritional Status, and Other Clinical Variables in the
Values are expressed as mean
Ϯ SD unless otherwise noted.
a P Ͻ 0.05 versus baseline values of treatment group.
b P Ͻ 0.05 versus control group.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Antidepression Treatment and Malnutrition in Hemodialysis Patients
which are well-known markers of dietary protein
This study is limited by its small sample size and
intake and body protein stores in steady-state
lack of an appropriate control group. Our study
chronic hemodialysis patients. Antidepression treat-
population was recruited from the single outpatient
ment also significantly increased ICF volume mea-
hemodialysis unit in which all patients had intimate
sured by BIA. The hydration state of the ICF reflects
relationships with each other and most of the pa-
water volume occupying the body cell mass, and the
tients who were diagnosed as having depression
changes occur because of changes in the anabolic-
wanted antidepression treatment. Because psychos-
catabolic state due to nutritional factors or illness.23
ocial support and compliance are associated with
Therefore, the rise in ICF volume shown in this
reduced mortality in chronic hemodialysis pa-
study could reflect an increased anabolic state.
tients,30 our antidepression treatment included sup-
Overall, these findings suggest that antidepression
portive group psychotherapy as well as antidepres-
treatment has therapeutic potential for the manage-
sant medication. Therefore, we could not assign
ment of malnutrition in chronic hemodialysis pa-
patients with depression to a placebo-treated control
There is some evidence that major depression is
accompanied by activation of the inflammatory re-
sponse system and that proinflammatory cytokinesmay play a role in the etiology of depression.24,25
Our study suggests that antidepressant medica-
Proinflammatory cytokines, which are commonly in-
tion with supportive psychotherapy can successfully
creased in ESRD patients, are responsible for the
treat depression and improve nutritional status in
increased protein catabolism, poor oral intake, and
chronic hemodialysis patients with depression.
malnutrition in maintenance hemodialysis pa-
Greater attention to the screening of depressive
tients.12 Accordingly, proinflammatory cytokine-in-
symptoms in chronic hemodialysis patients and the
duced chronic inflammation could be a common
initiation of appropriate antidepression treatment
cause of both depression and malnutrition in chronic
may be needed. A large, controlled multicenter
study to evaluate the effect of this therapeutic ap-
It is also known that different classes of antidepres-
proach on the mortality and morbidity in chronic
sants, including selective serotonin reuptake inhibi-
hemodialysis patients is required. To clarify the
tors, reduce the release of proinflammatory cytokines
exact role of depression and antidepressant treat-
from activated macrophages and increase the release
ment in the pathogenesis and management of mal-
of endogenous cytokine antagonists such as interleu-
nutrition in chronic hemodialysis patients, further
kin-1 receptor antagonist and interleukin-10.26–28
confirmatory studies, including measurement of in-
Therefore, antidepressants could reduce cytokine-
flammatory markers and cytokine levels, are also
induced protein catabolism, which will result in im-
provement of nutritional status in chronic hemodialy-sis patients. Because improvement of depressive
symptoms is usually accompanied by increased oralintake, both decreased protein catabolism and in-
creased protein intake could be possible mechanisms
Seung-Nam Cho, RN, of Hallym University Hospital
of the beneficial effect of antidepression treatment
for their assistance with the study.
shown in this study. Unfortunately, indicators of in-flammation such as serum high sensitivity C-reactive
protein level and change in dietary habits were notmeasured, and the authors wish to acknowledge the
1. Kimmel PL, Weihs K, Peterson RA.
Survival in hemodi-
speculative nature of this statement.
alysis patients: the role of depression. J Am Soc Nephrol
Paroxetine is a selective serotonin reuptake inhib-
itor that was chosen because of its ease of adminis-
2. Finkelstein FO, Finkelstein SH.
Depression in chronic
tration (once-daily dosing), absence of active metab-
dialysis patients: assessment and treatment. Nephrol DialTransplant 2000;15:1911–3.
olites, and favorable side-effect profile, including
3. Kimmel PL.
Psychosocial factors in adult end-stage renal
lower levels of cardiotoxicity than tricyclic antide-
disease patients treated with hemodialysis: correlates and
pressants.29 However, the initial dose of 10 mg was
outcomes. Am J Kidney Dis 2000;35(Suppl 1):132– 40.
maintained without dose modification during the
4. Ruberman W, Weinblatt E, Goldberg JD, et al.
course of this study because of possible side effects
ocial influences on mortality after myocardial infarction.
and drug interactions. This relatively small dose
and the short duration of treatment might be causes
5. Covinsky KE, Kahana E, Chin MH, et al.
symptoms and 3-year mortality in older hospitalized patients.
of insignificant change in SDS score. If higher dose
and longer duration of paroxetine was used, more
6. Peterson RA, Kimmel PL, Sacks CR, et al.
significant changes in the severity of depression and
perception of illness and mortality in patients with end-stage
nutritional parameters could be expected.
renal disease. Int J Psychiatry Med 1991;21:343–54.
January 2005 Volume 329 Number 1
7. Kimmel PL, Peterson RA, Weihs KL, et al.
19. Song JH, Lee SW, Kim GA, et al.
Measurement of fluid
measurements of depression predict mortality in a longitudi-
shift in CAPD patients using segmental bioelectrical imped-
nal study of chronic hemodialysis patients. Kidney Int 2000;
ance analysis. Perit Dial Int 1999;19:386 –90.
20. Kennedy SH, Craven JL, Rodin GM, et al.
8. Lopes AA, Bragg J, Young E, et al.
Dialysis Outcomes and
sion in renal dialysis patients: an open trial of antidepressant
Practice Patterns Study (DOPPS). Depression as a predictor
therapy. J Clin Psychiatry 1989;50:60 –3.
of mortality and hospitalization among hemodialysis patients
21. Blumenfield M, Levy NB, Spinowitz B, et al.
in the United States and Europe. Kidney Int 2002;62:199 –
in depressed patients on dialysis. Int J Psychiatry Med 1997;
9. Wuerth D, Finkelstein SH, Ciarcia J, et al.
22. Watnick S, Kirwin P, Mahnensmith R, et al.
and treatment of depression in a cohort of patients main-
lence and treatment of depression among patients starting
tained on chronic peritoneal dialysis. Am J Kidney Dis 2001;
dialysis. Am J Kidney Dis 2003;41:105–10.
23. Mehta RL, Jaeger JQ.
Dry weight and body composition in
10. Chertow GM, Johansen KL, Lew N, et al.
hemodialysis: a proposal for an index of fluid removal. Semin
tional status, and survival in hemodialysis patients. Kidney
24. Maes M.
Major depression and activation of the inflamma-
11. Rocco MV, Paranandi L, Burrowes JD, et al.
tory response system. Adv Exp Med Biol 1999;461:25– 46.
status in the HEMO Study cohort at baseline. Hemodialysis.
25. Seidel A, Arolt V, Hunstiger M, et al.
and serum proteins in depression. Scand J Immunol 1995;41:
12. Owen WF Jr, Lew NL, Liu Y, et al.
The urea reduction
ratio and serum albumin concentration as predictors of mor-
26. Leonard BE.
The immune system, depression and the action
tality in patients undergoing hemodialysis. N Engl J Med
of antidepressants. Prog Neuropsychopharmacol Biol Psychi-
13. Koo JR, Yoon JW, Kim SG, et al.
Association of depression
27. Xia Z, De Poere JW, Nassberger L.
TCA’s inhibit IL-1,
with malnutrition in chronic hemodialysis patients. Am J
IL-6 and TNF release in human blood monocytes and IL-2
and interferon in T-cells. Immunopharmacology 1996;34:27–
14. Hamilton M.
A rating scale for depression. J Neurol Neuro-
15. Zung W.
A self-rated depression scale. Arch Gen Psychiatry
28. Suzuko E, Shintani F, Kamba S, et al.
Induction of inter-
leukin-1 beta and intedeukin-1 receptor antagonist mRNA by
16. Zoccali C, Postorino M.
Electronic publishing: now and
chronic treatment with various psychotropics in widespread
tomorrow. Nephrol Dial Transplant 1998;13(Suppl 1):25–9.
areas of rat brain. Neurosci Lett 1996;215:201– 4.
17. Cha K, Chertow GM, Gonzalez J, et al.
29. Leonard BE.
Pharmacological differences of serotonin re-
bioelectrical impedance estimates the distribution of body
uptake inhibitors and possible clinical relevance. Drugs 1992;
water. J Appl Physiol 1995;79:1316 –9.
18. Zhu F, Schneditz D, Wang E, et al.
Validation of changes in
30. Kimmel PL, Peterson RA, Weihs KL, et al.
extracellular volume measured during hemodialysis using a
factors, behavioral compliance and survival in urban hemo-
segmental bioimpedance technique. ASAIO J 1998;44:541–5.
dialysis patients. Kidney Int 1998;54:245–54.
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