Antidepressant Treatment Increases Quality of Life in Patients with Chronic Renal Failure

Abstract

To evaluate the effect of citalopram treatment on quality of life (QoL) and depression in 141 patients with chronic renal failure (CRF), QoL was measured by means of the Short Form 36 (SF-36). Patients diagnosed with depression were treated with citalopram for eight weeks and evaluated for the effect of treatment on depressive symptoms and QoL. Thirty-four of 141 patients (24.1%) had depression and treatment with citalopram decreased Beck Depression Inventory Scores and increased the emotional role limitation and the mental health subscale scores of SF-36. This study suggests that citalopram can treat depression and improve QoL in patients with CRF.

Keywords:

• antidepressant treatment
• depression
• quality of life
• chronic renal failure
• citalopram

INTRODUCTION

It is known that psychosocial problems can be accompanied by organic disorders in patients with chronic renal failure (CRF). These, in turn, decrease quality of life (QoL) as well as compliance with treatment and prognosis.[1–3] It has been shown that the most common psychiatric disorder in CRF patients is depression.[4–6]

Chronic kidney disease (CKD) can cause significant changes in daily lives of the patients and affect the self-perceived QoL of the patients. In many studies, it has been shown that QoL of dialysis patients is worse than the healthy controls.[7],[8] The impairment in QoL can be related to CKD and its associated diseases as well as to the treatment.[9],[10] The impairment of the QoL in continuous ambulatory peritoneal dialysis (CAPD) patients might be explained by factors such as being primarily responsible for the management of the disease, the need to be dialyzed daily, and associated medical complications such as peritonitis. The QoL is lower in hemodialysis (HD) patients, presumably due to the factors such as being dependent on a dialysis unit, witnessing deaths at HD units, and associated medical illnesses. The obligation to make monthly outpatient visits and anxiety of being bound to HD machine in the near future may have a negative effect on QoL in patients with CKD in predialysis phase. In chronic renal failure patients, age, anaemia, physical symptoms (e.g., fatigue, loss of energy), erectile dysfunction, and limitation of social life are the main factors that affect QoL.[11]

During all stages of CKD, it is crucial to keep the QoL of the patients at the highest possible level. It has been reported in dialysis patients that QoL is an important factor that predicts morbidity and mortality,[12] and it was emphasized in many studies that depression was a significant factor that influences QoL in dialysis patients.[13],[14]

Several cross-sectional studies have reported the association between depression and QoL in dialysis patients. However there is no sufficient data about the effect of antidepressant treatment on quality of life in such patients.[15–17]

The objective of this study is to evaluate the effect of citalopram treatment on quality of life in depressed chronic kidney disease patients in predialysis phase or undergoing treatment either by HD or CAPD in the Nephrology Department of Kocaeli University Medical Faculty.

MATERIALS AND METHODS

Patients

Sixty-eight patients on hemodialysis (HD), 47 patients on continuous ambulatory peritoneal dialysis (CAPD), 26 patients with chronic kidney disease (CKD) on conservative management (total: 141 patients) and 66 healthy controls were enrolled in the study. These patients were followed up for more than six months at the Dialysis Centre and outpatient clinic of the Medical Faculty of Kocaeli University in Kocaeli, Turkey. Patients with acute illness; are older than 65 years; have an organic mental, psychotic, or bipolar disorder, or are pregnant were excluded from the study. Four patients with major depressive disorder who refused to complete the depression scale inventory were also excluded. Healthy control group was comprised of the staff from the Department of Internal Medicine, Medical Faculty of Kocaeli University, and the relatives of the patients.

This prospective study, approved by the ethics committee of the Medical Faculty of Kocaeli University, was conducted between October 2002 and June 2003. Written informed consent was obtained from each participant.

Causes of chronic renal failure were diabetic nephropathy in 24.8%, chronic glomerulonephritis in 10.1%, polycystic kidney disease in 9.2%, stone disease in 8.3%, hypertension in 5.5%, chronic pyelonephritis in 3.7%, amyloidosis in 3.7%, vesicoureteral reflux in 2.8%, miscellaneous in 5.4%, and unknown in 24.8% of the patients.

All the patients on HD received four hours of HD treatment three times per week, used bicarbonate-containing dialysis solutions, and were dialyzed with a cellulose acetate membrane. Most CAPD patients were prescribed two liters of exchanges 4–5 times daily. All patients received peritoneal dialysis via a Tenckhoff coil catheter. CAPD patients used a Baxter's Ultra Bag system (Baxter Healthcare Co., Deerfield, Illinois, USA) or Fresenius's Freedom Y set system (Fresenius Medical Care, Bad Homburg, Germany).

METHODS

Scales

Short Form-36 (SF-36)

The SF-36 instrument consists of 36 questions, 35 of which are compressed into eight multi-item scales:

1. Physical Functioning (PF) is a 10-question scale that captures abilities to deal with physical requirements of life, such as to attend to personal needs, walking, and flexibility.

2. Role—Physical (RP) is a four-item scale that evaluates to what extent the physical capabilities limit activity.

3. Bodily Pain (BP) is a two-item scale that evaluates the perceived amount of pain experienced during the most recent four weeks and to what extent the pain interfered with normal activities at work.

4. General Health (GH) is a five-item scale that evaluates general health in terms of personal perception.

5. Vitality (VT) is a four-item scale that evaluates feeling of pep, energy, and fatigue.

6. Social Functioning (SF) is a two-item scale that evaluates the extent and amount of time, if any, that physical health or emotional problems interfered with interactions with family, friends, and other social interactions during the most recent four weeks.

7. Role—Emotional (RE) is a three-item scale that evaluates the extent, if any, to what emotional factors interfere with work or other activities.

8. Mental Health (MH) is a five-item scale that evaluates principally feelings of anxiety and depression.

A Turkish version of SF-36 has been developed and reliability coefficients were found to be between 0.77–0.93.[18] The higher the scale, the better the QoL.

DSM-IV Structured Clinical Interview Scale (SCID-I) for Axis I Disorders

All patients were evaluated for the presence of depression using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Axis I DisordersClinician Version (SCID-CV).[19] The SCID-CV is partly semi-structured and based on clinical evaluation (not on simple yes/no answers to structured questions). The Turkish validation and reliability studies of the scale were performed by Corapcıoğlu et al.[20]

Beck Depression Inventory (BDI)

The severity of depressive symptoms was assessed using the Beck Depression Inventory (BDI). The BDI is a 21-item self-report rating inventory measuring characteristic attitudes and symptoms of depression. The 21 items are answered on a four-point Likert scale in which 0 represents the absence of a problem and 3 represents an extreme problem, with a total score range of 0–63 (normal score, 5–9; mild to moderate depression, 10–18; moderate to severe depression, 19–29; and severe depression, 30–63. The BDI is a well-validated index of depression and correlates well with the diagnostic criteria.[21] The validation and reliability study in a Turkish population was made by Hisli et al., and a BDI score of 17 or greater was used as a cutoff value for diagnosis of depression.[22]

Those patients diagnosed with Major Depressive Disorder according to the evaluations were informed of their diagnosis and the potential benefit of treatment as well as an eight-week treatment protocol. Citalopram 20 mg/day was given for eight weeks to patients who accepted the treatment protocol and gave informed consent. These patients were evaluated for the effect of antidepressant treatment on depressive symptoms and quality of life after the treatment period.

Statistics

All variables were summarized as mean ± standard deviation. The median values were also presented for the variables that showed non-normal distribution. The sociodemographic and clinical variables of patients were analyzed with descriptive statistics, chi-square test, Mann Whitney U test. Differences between the groups with and without depression were analyzed by Mann Whitney U test. For the comparison of more than two groups, we used Kruskal-Wallis nonparametric ANOVA. For the post-hoc test, we used Bonferroni corrected Mann Whitney U test. SF-36 subscales and BDI scores of patients at baseline were compared with scores after four and eight weeks of treatment by means of Wilcoxon signed ranks test. SPSS 11.0 program was used for statistical analysis, and a p value less than 0.05 was accepted as statistically significant.

RESULTS

Patient characteristics and differences in the Beck Depression Inventory (BDI) scores between patients with and without depression were summarized in Table 1. A total of 34 of 141 patients (24.1%) had depression. The distribution of mean age, gender, and other demographic variables were similar in patients with depression and without depression. The mean BDI scores were higher in patients with depression compared to those without depression (see Table 1).

Table 1 Patient characteristics and differences in the BDI scores between patients with and without depression

	With depression (n = 34)	Without depression (n = 107)	p
Clinical variables
Age (years)	48.2 ± 14.9	50.3 ± 15.1	NS
Male (%)	44.1	61.7	NS
Duration of therapy (months)	35.2 ± 95.4 (15)	23.2 ± 29.5 (15)	NS
Severity of depression
BDI score	45.8 ± 10.8	32.0 ± 8.7	<0.001

Note. Values expressed as mean ± SD unless otherwise noted. For parameters with non-normal distribution, median values are shown in parentheses.

NS = not significant.

All dimensions of QoL were worse in the patient groups, as compared to the control subjects (see Table 2). The mean scores of all SF-36 subscales were also lower in the patients with depression than the patients without depression (see Table 2). The mean age and percent of male gender of controls is 51.7 ± 12.4 years, 54.5% respectively. Other demographic variables were similar in patients groups and controls.

Table 2 The SF-36 scores of patient groups and controls

	With depression (n = 34)	Without depression (n = 107)	Control (n = 66)	p
SF-36 subscales
Physical functioning	38.5 ± 26.2	64.4 ± 28.3	87.1 ± 16.6	<0.001
Role—physical	24.2 ± 37.2	55.7 ± 42.1	89.4 ± 22.0	<0.001
Bodily pain	42.7 ± 27.8	70.8 ± 28.1	75.7 ± 21.1	0.012
General health	26.4 ± 18.5	49.5 ± 22.4	69.8 ± 17.1	<0.001
Vitality	32.7 ± 18.8	58.9 ± 25.0	67.1 ± 18.1	<0.001
Social functioning	45.1 ± 31.6	69.3 ± 28.1	85.4 ± 16.1	0.004
Role—emotional	21.2 ± 34.2	60.0 ± 41.2	84.3 ± 29.9	0.003
Mental health	41.1 ± 19.4	67.6 ± 20.5	70.9 ± 15.6	0.007
Physical summary score	33.0 ± 18.1	60.1 ± 23.4	80.5 ± 14.3	<0.001
Mental summary score	35.0 ± 17.2	63.0 ± 23.9	77.0 ± 14.4	<0.001
Total summary score	34.0 ± 15.6	62.0 ± 22.5	78.7 ± 13.3	<0.001

All of the patients with depression accepted treatment, and antidepressant treatment was commenced after their consent. After eight weeks of citalopram treatment, the mean BDI score decreased (p = 0.030; see Table 3).

Table 3 Depression scores of patients undergoing citalopram treatment

	Week number	N	Mean	SD	p
Beck Depression Inventory	0	34	45.8	10.8	—
	4	24	42.8	9.1	0.079
	8	20	38.5	11.3	0.030

In patients taking citalopram treatment, scores of emotional role limitation and mental health subscales of SF-36 were higher in week 8. Physical role limitation and pain subscores of SF-36 also increased with treatment (p = 0.047 and p = 0.013, respectively; see Table 4). During the eight-week treatment, no adverse effect requiring drug cessation was seen in the study group.

Table 4 SF-36 Quality of Life Scale scores of patients undergoing citalopram treatment

	Week number	N	Mean	SD	p
Physical functioning	0	34	38.5	26.2	—
	4	24	38.5	27.1	0.22
	8	20	38.0	28.2	0.31
Physical role limitation	0	34	24.2	37.2	—
	4	24	40.6	43.5	0.25
	8	20	46.3	40.0	0.30
Pain	0	34	42.7	27.8	—
	4	24	53.0	31.6	0.64
	8	20	60.9	34.4	0.13
General health	0	34	26.4	18.5	—
	4	24	33.3	14.9	0.17
	8	20	36.7	26.0	0.3
Vitality	0	34	32.7	18.8	—
	4	24	38.1	18	0.54
	8	20	44.5	19.1	0.18
Social functioning	0	34	45.1	31.6	—
	4	24	47.9	25.5	0.28
	8	20	63.8	23.6	0.14
Emotional role limitation	0	34	21.2	34.2	—
	4	24	41.7	39.6	0.07
	8	20	50.0	42.6	0.047
Mental health	0	34	41.1	19.4	—
	4	24	52.5	17.9	0.05
	8	20	61.0	21.4	0.013

DISCUSSION

It is known that the most common psychiatric problem in dialysis patients is depression, which is estimated to be present in 20–30% of patients.[23],[24] Sagduyu and Erten investigated the prevalence of mental disorders in Turkish patients with chronic renal failure and confirmed that depression is the most common psychiatric disorder with a prevalence of 17.1%.[25] In our study, a total of 34 of 141 patients (24.1%) had depression.

There has been growing interest in the QoL in chronically ill patients in recent years. It was emphasized in many studies that depression was a significant factor that influences QoL in dialysis patients.[13],[14] We found that the mean scores of all SF-36 subscales were lower in patients with depression than in those without it.

The results of this study demonstrate that citalopram at a daily dose of 20 mg is effective in treating CRF patients with depression. Spigset et al. showed that severe renal failure did not affect the pharmacokinetics of citalopram, and they suggested that modification of the usual citalopram dose did not seem to be necessary.[26] In the same study, the contribution of hemodialysis to the total elimination of citalopram was found to be negligible. In their review about drugs that could be used in transplant patients for depression and anxiety, Crone and Gabriel note that citalopram and escitalopram carried the lowest risk for drug-drug interactions and thus could be used in this population.[27]

Studies indicated that the psychiatric evaluation and follow-up of dialysis patients includes several difficulties. In a study by Wuerth and colleagues, the prevalence of depression in 136 CAPD patients was investigated by using BDI.[28] In 67 of the patients, BDI scores indicated possible depression, and these patients were suggested psychiatric evaluation. However, only 25 of these patients accepted psychiatric evaluation. In 22 of the 25 patients (85%), clinical depression was diagnosed. Again, only 12 of these patients accepted antidepressant treatment. Eleven of the original 12 patients completed the 12-week antidepressant trial, and all had significant decreases in their BDI scores. Another study by the same group had similar results, with 134 of the 320 patients having BDI scores indicating possible depression, 69 of these agreeing for further evaluation, and 60 of these being diagnosed with depression.[29] However, only 44 of these agreed to treatment, and only 23 of these 44 successfully completed a 12-week antidepressant trial. The reasons for high rate of noncompliance and dropout was subsequently reviewed, and the authors have proposed that refusal for further psychiatric evaluation in patients undergoing dialysis may be due to denial of depression, unwillingness to use additional drugs, regarding depression as a sign of mental illness or weakness, and fearing stigmatization.[26] Similar to the studies done in the United States, four patients refused the psychiatric evaluation in our sample. The refusal of the psychiatric evaluation in these four patients is probably due to a fear of stigmatization, regarding depression as a sign of mental illness. Contrary to the studies done in the United States, all depressive patients in our sample accepted antidepressant treatment. We feel that this may be due to the cultural profile of the sample as well as perceiving the physician as a higher authority. Although all depressive patients were started on antidepressant treatment, fourteen of these patients could not complete the antidepressant trial (41.27%), indicating a dropout rate similar to the other studies. Wuerth and colleagues suggested that noncompliance may be due to acute medical problems, active substance abuse, drug side effects, and axis II personality disorders.[29] Reasons for noncompliance in our sample may be due to an unwillingness of additional drug usage, acute medical problems, and axis II personality disorders. Because only SCID-I-CV was applied to patients, we refrain from making inferences about the prevalence of axis II disorders.

Level of depression decreased and quality of life was increased in the patients who completed treatment after eight weeks. In those patients completing treatment, BDI scores decreased significantly after eight weeks of treatment. This finding is similar to previous reports.[17],[27],[28] We also showed that antidepressant treatment increased the quality of life of dialysis patients in our sample. In the SF-36 scale, scores of emotional role limitation and mental health subscales were significantly increased in week 8. Other scores showed increase with treatment, although these were nonsignificant. The physical role limitation scores were unchanged as expected, due to the psychiatric nature of treatment.

Although the association between depression and QoL in dialysis patients is investigated in several studies, to our knowledge there is only one report in which the effect of antidepressant treatment on QoL is determined.[14–16] That study's conclusions were similar to ours: it was found that the QoL parameters were improved after antidepressant treatment with sertraline.[30]

The main limitation of our study is the lack of a control group in the treatment period. Because the number of patients with depression in our study group was small, we did not attempt to have subgroups treated with antidepressants other than citalopram. Further studies with different control groups consisting of patients without renal diseases treated with citalopram and patients with a renal disease treated with other antidepressants may shed light on this subject.

In conclusion, chronic renal failure causes psychiatric problems and impairs quality of life. This study suggests that antidepressant therapy with citalopram can treat depression and improve QoL in patients with chronic renal failure.

ACKNOWLEDGMENTS

The authors would like to thank Assoc. Prof. Dr. Oktay Ozdemir from Omega Contract Research Organization for performing the statistical analyses.