INTRODUCTION
Depression is a common mental disorder that is characterized by persistent sadness and lack of interest or pleasure in previously enjoyable activities [1]. Anxiety disorders are by definition a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear [2]. These two mental disorders are common problems, with an estimated prevalence of about 20% of cases among hemodialyzed patients [3], and they significantly contribute to the morbidity and mortality among them [4]. The symptoms of psychiatric diseases in this context were often overlooked in the past [3], however in recent years the subject has gained more scientific attention. One of the main reasons is the fact that depression co-occurring with chronic diseases may be more resistant to treatment [5, 6], also it might have negative correlation with patients’ quality of life [7]. Furthermore, it has been reported that depression among patients with end-stage renal disease, including patients undergoing hemodialysis, correlates with decreased survival rate [8] and adherence to dialysis-connected medication [9]. The main factors that contribute to the development of depressive symptoms are reduced well-being through the need of medication, reduction of physical function, and dietary restrictions [10], all of which are aspects of daily struggles of hemodialyzed (HD) patients and may explain high prevalence of depression among them. All of this indicates the importance of identifying and treating depressive disorders and symptoms of anxiety. In order to screen patients, physicians may use one of the validated tools such as the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMS). Although they are not substitutes for psychiatric examination, these clinician-rated scales may prove to be useful in identifying the first symptoms of psychiatric disorders [4]. The purpose of this literature review is to shed more light on this matter by increasing the awareness of clinicians in these matters, as well as to demonstrate some of the proposed methods of treatment. The search included all available English-language articles reporting on depression and anxiety among hemodialyzed patients. The following databases were searched: Medline, Scopus and Web of science. In order to be included they had to meet following criteria: a) patients had been undergoing hemodialysis, b) were over 18 years old, and c) experienced clinical depression or anxiety disorders including generalized anxiety disorder and panic disorder. The exclusion criteria were a) studies were not reported in English, and b) peritoneal dialysis was included.
PHARMACOLOGICAL METHODS
There are many possible causes as to why it is difficult to recognize and deal with depression and anxiety among patients undergoing hemodialysis [11]. Although there are many scales which physicians can use to estimate the prevalence of major depressive disorder, there is no consensus as to which tool is the most accurate [11, 12]. In fact, studies show that the findings on prevalence of this disorder are highly depended on the method used [12]. Another problem faced by clinicians is the treatment of depression and anxiety among patients with chronic kidney disease (CKD). There are a few studies discussing psychotherapeutic and pharmacological interventions and their effectiveness [13]. Unfortunately, the data on the effectiveness of antidepressants is limited due to the lack of randomized studies on larger populations [14]. However, there are ongoing trials of sertraline, bupropion and fluoxetine treatment among dialyzed patients, which will evaluate effectiveness and adverse events, the findings of which are highly anticipated [15, 16]. Another reason for the lack of data is the fact that patients with end-stage renal disease are often excluded from the clinical trials due to safety concerns [17]. Selective serotonin re-uptake inhibitors (SSRIs) are mostly excreted by the liver and are not influenced by renal dysfunction [18]; however, the elimination half-life is prolonged and the clearance after oral intake is reduced for many antidepressants such as selegiline [19], amitriptylinoxide [20], venlafaxine [21], desvenlafaxine [22], milnacipran [23], bupropion [24] and reboxetine [25, 26]. This may contribute to the higher prevalence of mild adverse effects of the treatment, though no study reported discontinuation as a consequence of side-effects of the therapy [14, 26]. The results of those reports suggest that the risk-benefit ratio may be different in comparison to the general population [27] and should be calculated individually. Another important matter is the challenge of adherence to treatment, as the majority of patients do not make a regular use of the treatment prescribed [18, 28]. Apart from the treatment of depressive symptoms, studies show that some SSRIs such as sertraline have anti-inflammatory effects and decrease C-reactive protein (CRP) levels [29]. It is worth noting that long-term hemodialysis treatment might be connected to increased levels of interleukin 1 (IL-1), IL-6 and CRP, which in turn contribute to negative nitrogen balance due to the catabolism of body protein, causing malnutrition and decreased appetite [30]. Since malnutrition is an important factor contributing to morbidity and mortality it is crucial to regularly assess the nutritional status of hemodialyzed patients [31, 32]. The European Renal Best Practice statement from 2014 recommends the use of selective SSRIs for 8 to 12 weeks and reevaluation after 12 weeks of therapy [11, 26].
Another matter is the treatment of anxiety disorders, which is complex and varies depending on the characteristics of the patient. The current guidelines recommend the use of SSRIs and serotonin and norephinephrine reuptake inhibitors (SNRIs) as the first-line treatment [33]. The examples of medications commonly used in clinical practice with their indications, contraindications and side-effects are listed in Table 1. Benzodiazepines are considered to be second-line treatment for anxiety disorders, especially in generalized anxiety disorders and patients with specific phobias [34], though they should not be use in the treatment of chronic conditions due to their addictive potential [35, 36]. Anxiety treatment among hemodialyzed patients poses challenges as there are no randomized studies regarding this topic. Pharmacological treatment may be carefully implemented following individual evaluation, with consideration to dose reduction to avoid medication-dosage errors and their consequences [3].
Table 1
Antidepressants commonly used in medical practice with their indications, contraindications, adverse effects and the need of adjustment of dosages in case of renal dysfunction
NON-PHARMACOLOGICAL INTERVENTIONS
Pharmacological methods seem to be important means of treatment of depression among HD patients; however, due to the lack of randomized studies and concerns arising from using antidepressants among those patients, non-pharmacological ways of treatment have been taken into consideration. There are a small number of reports investigating psychosocial interventions, which are described as non-medical interventions that are psychologically, socially, behaviorally or educationally oriented, among patients with CKD [37]. One of the most popular and well-documented non-pharmacological treatment methods is cognitive-behavioral therapy (CBT), which helps to reorganize negative thoughts and support behavioral adjustments and logical thinking [38, 39]. A study conducted in Brazil showed that CBT is an effective method of treatment among HD patients, causing a significant decrease of depressive symptoms and contributing to increased quality of life among them [40]. CBT also contributes to deceased anxiety levels. Different studies suggest that cognitive-behavioral therapy is effective after at least 6 to 9 months of treatment. A decrease in symptoms of depression here is probably achieved by encouraging patients to talk about their thoughts, and reorganizing those thoughts that might be interfering with their mood and daily behaviors, as well as creating coping strategies to deal with kidney disease, dialysis treatment, and depression [40]. A large study assessed different non-pharmacological interventions such as acupuncture, acupressure, physical exercises or relaxation techniques including progressive muscle relaxation, breathing exercises, visualizations and autogenic training. It was reported that these relaxation techniques and physical exercises showed, to some extent, an improvement in depressive symptoms and anxiety levels [41]; however, the evidence produced by this study was insufficient for the determination, with high level of certainty, of the impact of the interventions concerned. The findings of this study match the results of another meta-analysis, in which authors showed the positive impact of psychosocial interventions on the treatment of both depression and anxiety among patients with CKD [42]. The outcomes were matched by yet another meta-analysis in regard of anxiety and depression, where there was no significant difference between HD patients receiving psychological interventions and the control group [43]. The assessment of the impact of psychosocial interventions is challenging, as studies on this topic are scarce. All of the studies have small sample groups and in most of them the adverse effects of some of methods were not included in the analysis. Neither was the change in suicide rate [42]. Thus, the outcomes of those reports should be treated with caution. Another interesting topic that is generally not reported is the usage of both pharmacological and psychological methods of treatment combined. Studies show that the effects of the combination of these two methods of treatment are superior to each strategy alone in the general population [41]. However, there are no reports of the efficacy of such combined treatment among hemodialyzed patients.
There are only a few reports about non-pharmacological forms of anxiety treatment among HD patients. According to some studies, psychosocial interventions are an effective tool in reducing anxiety levels in the general population [44]. Moreover, some of the analyses suggest that CBT is the most effective method after comparing the long-term results of different interventions [45]. There are also only a small number of studies that investigate the efficacy of non-pharmacological methods in reducing anxiety levels among hemodialyzed patients, though these also underline the suggestion that CBT is probably the most effective form of treatment [46]. There is also one study that compares the efficacy of CBT versus sertraline usage in anxiety treatment among HD patients, though the results of the study have not yet been published [47]. These results must be regarded with caution, as there are no randomized trials on psychosocial interventions among HD patients and additional studies are needed. However, considering their positive effect on depressive symptoms they may be useful in increasing patients’ quality of life.
CONCLUSIONS
Even though the number of studies on this topic is gradually increasing, depression and anxiety are still largely under-recognized in hemodialyzed patients. It must be remembered that both of those problems contribute to decreased quality of life, poorer adherence to the treatment programs, and thus to higher rates of morbidity and mortality among those patients. This is why it is essential to evaluate hemodialyzed patients, so as to recognize the presence of alarming symptoms. Moreover, it is crucial to implement effective measures in reducing anxiety levels and manifestations of depression. Due to the lack of randomized studies and absence clear guidelines, however, this may prove difficult. That is why the purpose of this review was to present both pharmacological and non-pharmacological methods of treatment of depression and anxiety among hemodialyzed patients. The results of the studies discussed should be treated with caution, and the methods suggested should only be employed after the individual examination of each patient. Moreover, in the case of pharmacological treatments dose reduction may be considered due to decreased renal function found among this group of patients [48]. This study, like the limited number of studies that have preceded it, demonstrates the urgent need for randomized clinical trials of both psychosocial and pharmacological interventions in the treatment of depressive and anxiety disorders.
