**3. Depression**

Depression is a common mental disorder worldwide. According to the American Psychiatric Association, depression is a common illness that negatively affects feelings, thinking, and responses [12]. It is an emotional state marked by somatic and cognitive symptoms [13]. Depression is often known as major depressive disorder or clinical depression, which is widely underreported and underdiagnosed in many chronic illnesses.

The National institute of Mental Health indicates that depression has various types [14]. These are major depression, persistent depressive disorder, perinatal depression, seasonal affective disorder, and depression with symptoms of psychosis. The major depression is defined by symptoms that last at least 2 weeks and interfere with daily activities. More specifically, the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) in its latest version indicates that the diagnosis of a major depressive disorder should have two criteria. First, the symptoms should continue for a period of at least 2 weeks. Second, depressed mood should be experienced almost daily or be accompanied by a loss of interest in routine activities, as well as at least four of the additional symptoms listed below: (a) significant change in weight (either loss or gain) or change in appetite, (b) alteration in sleep pattern (e.g., insomnia), (c) psychomotor changes (i.e., agitation or retardation), (d) fatigue and loss of energy, (e) feelings of worthlessness or extreme guilt, (f) decreased concentration, or (g) thoughts of death or suicide [15] Cohen et al. noted that many of these symptoms that are associated with major depression could overlap with uremic symptoms in ESKD [16]. However, death and suicidal thoughts are more likely to be related to major depression. It is therefore important that clinicians be careful when they assess depression in this specific population.

The other type of depression is persistent depressive disorder, which is also called dysthymia, and is characterized by a lower severity of the depressive symptoms but a longer duration, typically at least 2 years. Perinatal depression is experienced by women and associated with specific times such as pregnancy and the postpartum period. Seasonal affective disorder has been linked to particular seasons. The last type is depression with symptoms of psychosis, which is the most severe type of depression in which psychosis symptoms also occur.

Depression in hemodialysis is contributed by numerous changes in the personal, social, and professional aspects, such as job loss, dietary changes, and sexual dysfunction, in addition to the frequent stressful experience of dialysis, the invasive procedure of dialysis, issues related to dialysis access, uncertainty about the future,

and anxiety regarding mortality. The adverse outcomes of depression among hemodialysis have been widely examined. Previous studies indicate that depression among dialysis patients is associated with poor treatment adherence [17, 18], high hospitalization rates [19], and lower quality of life [20, 21]. There is growing evidence that the depression is correlated with increased risk of mortality rates in hemodialysis [19, 21–24]. Cheng et al. found that cognitive symptoms of depression have a better predictive value of long-term mortality in people undergoing hemodialysis than somatic symptoms [25]. Collectively, the adverse effects of depression make it an important subject to address.

Globally, depression affects approximately 5% of adults and is the principal cause of disability [26]. Moreover, it is one of the most common mental disorders among hemodialysis patients. The prevalence of depression varies among countries. However, a large body of literature shows that depression affects about one-quarter of dialysis patients [27–29]. In the USA, the prevalence of depression among hemodialysis patients ranges between 14 and 44% [30, 31], and in Australia, it was found to be about 13.3% [32]. A multinational European study conducted in Portugal, Turkey, Italy, and France that examined depression among 2278 people with hemodialysis reported a prevalence as 46% [33]. Depression rates in Saudi Arabia ranged from 5.62% to 44.7% [34, 35]. Depression in hemodialysis was much higher in Africa, as it ranged between 45 and 76.3% [36]. The variation across these studies was due to the potential for variation in methodological designs applied and assessment measures utilized, in addition to other factors such as sex, race, educational level, and economic status.

#### **3.1 Screening and diagnostic measures**

There are several measures available to diagnose and screen for depression in hemodialysis units. The semistructured interviews are considered the goldstandard method of diagnosis for depression. These include the Mini International Neuropsychiatric Interview and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-1) [37]. These types of interviews should be conducted by wellskilled healthcare professionals who are familiar with the criteria for the diagnosis of major depression mentioned previously.

Given the dramatic changes in all aspects of life for people undergoing hemodialysis, it is recommended to screen for depression at the time of initiation, after 6 months, and then yearly [38]. It is also supported by prior evidence demonstrating that there is no correlation between any specific time since the commencement of dialysis and the occurrence of depression [39]. This requires ongoing examination of depression in hemodialysis patients throughout their treatment trajectory. Currently, the Beck Depression Inventory, Patient Health Questionnaire (PHQ-9), Center for Epidemiologic Studies Depression Scale (CES-D), and Hospital Anxiety and Depression Scale (HADS) are valid and reliable measures for screening of depression the dialysis population. Although the best one to use remains uncertain. These measures differ in their lengths and items, which make some of them more efficient for initial screening of depression.

The most commonly used measure to assess depression is the Beck Depression Inventory (BDI). It has been extensively used in screening patients with ESKD [40]. The BDI was developed in 1961 and consisted of 21 items [41]. Over time, the scale has been revised to be updated according to the new guidelines and diagnostic criteria for psychological disorders issued by the American Psychiatric Association. The

first version of BDI (BDI-I) was published in 1987. Then, the second version of BDI (BDI-II) was available in 1996 and included 21 items as well as a few items revised [41]. This scale evaluates responses on a 4-point Likert scale, where 0 means that no problem exists and 3 means that the problem is highly prevalent. The maximum score of the BDI-II is 63. The severity of the depression was classified based on the range of scores given. When the BDI-II score ranges from 0 to 13, it is considered minimal depression. When the score is between 14 and 19, it indicates mild depression. When a person's BDI-II score ranges from 20 to 28, they may be suffering from moderate depression. Severe depression is classified when the BDI-II score ranges from 29 to 63 [42]. In addition, a cutoff score of ≥11 was identified as sensitive point for determining the major depressive episode among patients with chronic kidney disease [43]. The BDI-II is a well-validated scale that has been used widely used to assess depression in people undergoing dialysis [44–49].

The latest version of BDI is known as BDI-FS, which is fast and short and includes only seven items. The scale of scoring is 0–3. The value of this version is to accelerate the screening for depression. This quick scale may be useful in identifying potential hemodialysis patients who are depressed [36, 50], and once identified, further testing should be performed to validate the diagnosis and initiate the appropriate intervention.

It was argued that developing a tool that focuses on non-somatic disturbances associated with depression while excluding somatic symptoms that could be caused by dialysis is critical. Accordingly, the Cognitive Depression Index (CDI) was developed by selecting a subset of 15 items from the BDI-II and excluding those related to somatic symptoms [37, 51]. The significance of this index was emphasized by both Kimmel et al. and Peterson et al., who found a correlation between high depression using CDI and increased mortality rates and lower survival rates in chronic kidney disease [52, 53].

Additional short and fast tool for screening of depression is the Patient Health Questionnaire (PHQ-9). It is a self-reported survey that includes nine items specific to depression. The responses are scored on a 4-point scale to indicate the severity of depression, with 0 for a statement indicating not at all and 3 indicating experience with a statement of nearly every day. A maximum score assumed for the PHQ-9 is 27. Using this measure, depression is classified into four categories. A score range between 1 and 4 indicates that there is no depression, a score range between 5 and 9 indicates a mild depression, a score range between 10 and 14 indicates a moderate depression, a score range between 15 and 19 indicates a moderately severe depression, and a score of 20 or more indicates a severe depression [54]. A previous study suggested that a cutoff point of 10 on the PHQ-9 is sensitive to detecting depressed patients [55]. As the PHQ-9 is also short, it is recommended to use it as a screening tool for depression in dialysis units.

Another well-known measure for assessing depression in hemodialysis is the Hospital Anxiety and Depression Scale (HADS). It was developed in 1983 by Zigmond and Snaith to evaluate both anxiety and depression levels in the outpatient units of the hospital [56]. HADS is a relatively short and quick instrument. It is a selfreported survey with 14 multiple-choice questions that have two subscales: anxiety (HADS-A) and depression (HADS-D). Each subscale includes seven items rated on a four-point scale (from 0 to 3), where 0 indicates the absence of the problem and 3 indicates the presence and severity of the problem. The maximum score given is 21. A score of 7 or less means absence of anxiety or depression; a score between 8 and 10 represents moderate levels of anxiety or depression; and score more than 11 reveals

high levels of anxiety or depression. The HADS is a valid tool, and extensive studies show that HADS is practical in the assessment of anxiety and depression among people undergoing hemodialysis [57–61].

Center for Epidemiologic Studies Depression Scale (CES-D) is one of the most common instruments used to assess depression. The Center for Epidemiological Studies-Depression (CES-D) created this scale to assess depression in 1977 by Radloff [62]. It comprises 20 items that evaluate the mood and somatic symptoms, interpersonal relationships, and motor functioning in the past week. The total score of the scale ranges from 0 to 60, with a higher score revealing worse psychological status. A cutoff value of ≥16 was approved to indicate depression. The scale was validated and used in many studies for patient undergoing hemodialysis [37, 63]. Other screening measures have been used to assess depression among hemodialysis patients using non-specific tools and parts of other tools, such as the Kidney Disease Quality of Life Questionnaire (KDQOL-SF), the SF-36, the Mental Health Inventory 5, and the Edmonton Symptom Assessment System.

It is important to notice that using self-reporting scales could result in overdiagnosis, especially among patients on dialysis. The daily symptoms experienced by those patients (e.g., fatigue, sleep disturbance, and difficult concentration) can overlap with the somatic symptoms of depression. Besides the symptom burden, the occurrence of other comorbid conditions may add to the complexity of the depression diagnosis in a patient on dialysis.

#### **3.2 Management of depression in hemodialysis**

The diagnosis and treatment of depression in hemodialysis are crucial because untreated depression is associated with poor adherence to management, increased morbidity and mortality rates, and a low quality of life among people undergoing hemodialysis. Generally, the management of depression has been classified into pharmacological and nonpharmacological interventions. Management approaches should be adapted to the patient's unique needs (e.g., treatment history, concurrent illnesses, and preferences of the patients and their family) and consider the resources available in the dialysis facilities [38].

#### *3.2.1 Pharmacological treatment*

Antidepressant drugs have been shown to be effective in treating depression in the general population [64]. However, in dialysis, this is still ambiguous. For safety concerns and the possibility of serious adverse events, there are few antidepressant trials conducted among hemodialysis patients to support their efficiency. The pharmacokinetics of antidepressant drugs in hemodialysis are likely to be affected due to several factors. In fact, the metabolism of antidepressant drugs is such that these drugs frequently go through the liver, and the active metabolites are eliminated by the kidneys instead [38]. Impaired kidney functions negatively influence the excretion process, which causes buildup toxic concentrations of the drug in the body. In addition, since antidepressants are typically heavily protein bound, dialysis does not significantly eliminate them from the body [38, 64]. Moreover, there is a high risk of drug-drug interactions in dialysis patients due to the polypharmacy taken for the treatment of kidney failure and associated comorbidities [38].

The selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressant drugs to use [36]. In hemodialysis, the SSRIs are still under debate [36, 65].

#### *Psychosocial Aspects in Hemodialysis DOI: http://dx.doi.org/10.5772/intechopen.109592*

Both meta-analyses and a recent systematic review revealed that the evidence related to SSRIs is not sufficient, and the findings are contradictory [66, 67]. Some placebocontrolled trials show low or ungradable benefits [66, 67]. Among the SSRIs, fluoxetine is the most researched, with a daily dose of 20–60 mg considered tolerable [16, 68]. Another review has focused on the use of sertraline in hemodialysis and found that the use of sertraline appears to be safe but needs more investigation [69]. A double-blind randomized clinical trial found that sertraline has improved pruritis intensity in hemodialysis patients [70]. Other examples of drugs in the same class are citalopram, escitalopram, fluvoxamine, and paroxetine. Despite the fact that there is insufficient evidence to support the efficacy of SSRIs in hemodialysis patients, they have fewer anticholinergic and cardiac side effects than other drugs, such as tricyclic antidepressants (TCAs), which adds to their privilege [65]. Further, a recent systematic review found that side effects for SSRIs were minor, such as fatigue and nausea [66]. Another reported side effect of SSRIs is an increased risk of bleeding, which requires cautious use in patients with platelet dysfunction [16]. Importantly, patients should be observed for any suicide attempts, as a risk of suicide during the SSRI treatment may potentially occur during the initial administration [39]. The initial treatment should be started with a low dose, and the clinical effects should be monitored closely for at least 4–6 months [16]. If the result is suboptimal, the dose may be increased or the drug changed [16, 65].

Selective norepinephrine reuptake inhibitors, such as venlafaxine and bupropion hydrochloride, are examples of a different class of antidepressants that are also used with caution [16, 39]. Monoamine oxidase inhibitors are used, but not preferred as they have many side effects, especially hypotension [16]. **Table 1** summarizes the antidepressant drug classes and recommended dosing in patients undergoing hemodialysis [68].

We should notice that depression could happen due to multiple factors, including triggers of other symptoms such as fatigue, sleep disturbance, and sexual dysfunction [71–74]. Given this, clinicians should comprehensively assess the potential correlating factors before prescribing any antidepressant medications. The possible management of depression may be conducted indirectly through the management of the source of the issue.

#### *3.2.2 Nonpharmacological interventions*

The optimal care to enhance mental health includes nonpharmacological interventions as a key component to reduce stress, improve cognitive function, and enhance coping. Nonpharmacological interventions have been considered due to safety concerns and a lack of evidence about the efficacy of pharmacological regimens for depression in hemodialysis patients. In contrast, many studies have shown that using these alternative approaches has significant clinical outcomes in the treatment of depression in hemodialysis patients [75–79]. These include cognitive behavioral therapy (CBT), psychoeducation, exercise programmers, relaxation training, acupuncture therapy, self-management, problem-solving, meditation and laughter therapies, and mindfulness-based stress reduction [36, 38, 66, 68, 80].

Cognitive behavioral therapy (CBT) is a common psychotherapy approach to depression treatment. The main principle of CBT focuses on resolving the cognitive factors that lead to psychological distress, such as coping and acceptance. It is based on an organized approach to encourage the restructuring of negative ideas, improve mental status, and enhance behavioral adaptations [68]. A growing body of evidence supports

