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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 ABSTRACT: Background: 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: Six- 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 Ͻ 0.005), 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 Conclusion: 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 INDEXING TERMS: 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- 2004;329(1):1–5.]
Depression 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: [email protected]). 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
Table 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 Ϯ 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.
Discussion
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 Table 2. 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- Conclusion
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 Acknowledgments
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 References
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