Patients with end stage kidney disease (ESKD) are affected by numerous psychosocial stressors. These include effects of illness and treatment, functional limitations and sexual dysfunction, dietary restrictions, time constraints, and fear of death. In addition, there may be marital conflict, strained interpersonal relationships with family and administrative or medical personnel, and socioeconomic concerns regarding costs of treatment and unemployment.

Approximately 10% of ESKD patients who are hospitalized have an underlying psychiatric disorder. Hospitalization rates for psychiatric disorders are high relative to other chronically ill patients. Common problems include depression, dementia and delirium, psychosis, personality and anxiety disorders, and substance abuse.

I. DEPRESSION. Depression is the most common, as well as the most important, problem because of the risk of resulting noncompliance with the dialysis and/or medication regimen and the risk of suicide. Depression may be widely underdiagnosed and untreated. According to the most recent version of the Diagnostic and Statistical Manual for Mental Disorder (DSM 5), a major depressive disorder should be diagnosed if, during a period of at least 2 weeks, a patient experiences depressed mood nearly every day or loss of interest/pleasure in usual activities and at least four of the following additional symptoms: (a) significant weight loss or weight gain or appetite disturbance, (b) change in sleep pattern, including insomnia or hypersomnia, (c) psychomotor agitation or retardation, (d) fatigue, (e) feelings of worthlessness or excessive guilt, (f) decreased concentration, or (g) recurring thoughts of death or suicide. The last criterion, (g), is probably the most specific, as some of the others are associated with uremia per se.

Some investigators have estimated that depression occurs in as many as 10%-50% of dialysis patients. Screening tools include the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression. In patients with no underlying medical problems, a BDI score <9 suggests no or minimal depression, 10-18 indicates mild to moderate depression, 19-29 moderate
to severe depression, and ≥30 severe depression. In patients with ESKD, the recommended cutoff scores for depression are higher, with BDI scores ≥14-16 indicating significant disease.

Screening for underlying depression in the dialysis population is an important element of the treatment plan. Depressive affect can influence medical outcomes in several ways. In addition to the risk of suicide, depression may lead to poor compliance with the dialysis prescription, to abnormal immunologic function, or to anorexia and poor nutritional status. Depressive affect has also been linked to a higher incidence of peritonitis. Whether depression increases mortality risk is controversial. Some studies have suggested that baseline depressive symptomatology is associated with increased mortality, even after multiple medical risk factors have been accounted for in analyses.

ESKD patients can display suicidal behavior differently from patients with other chronic illnesses. Their rate of suicide is higher than in the general U.S. population. Important risk factors include a previous history of mental illness, recent hospitalization, age >75, male gender, white or Asian race, and alcohol or drug dependence. ESKD patients presumably can commit or attempt suicide more easily either through noncompliance with their medical regimen or by manipulating their dialysis access sites.

A. Treatment options. Treatment options for depression include pharmacotherapy, psychotherapy, including cognitive behavioral therapy, and electroconvulsive therapy. Unfortunately, there are limited data on the effects of antidepressants in patients with ESKD, since these patients are often excluded from many of the large clinical trials.

1. Pharmacotherapy

a. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Treatment with SSRIs should be continued for at least 4-6 weeks before deciding whether there has been a therapeutic benefit. If efficacy is not achieved, then a switch to another antidepressant of the same class or a different class is a reasonable step. SSRIs are advantageous because they typically cause fewer anticholinergic symptoms than TCAs, and are not associated with cardiac conduction abnormalities. Furthermore, TCAs can cause death if taken in large doses and hence pose a potential suicide risk. However, there is a potential for increased bleeding in patients taking SSRIs, which may be relevant to patients with ESKD and preexisting qualitative platelet defects from uremia. SSRIs may also worsen nausea and vomiting, which are common symptoms in the dialysis patient population.

Typically, SSRIs are cleared by the liver and are highly protein bound. It has been recommended that the dose of SSRI in patients with ESKD should be reduced to two-thirds of the usual amount. SSRIs may have an additional benefit of reducing postural and intradialytic
hypotension through effects on vascular tone. Fluoxetine, the first available SSRI, is the best studied drug in this family. A dose of 20 mg of fluoxetine daily is usually well tolerated, although data are limited to the short term. Other medications in this same family include paroxetine, sertraline, and citalopram.

b. Selective norepinephrine reuptake inhibitors (SNRIs). Venlafaxine and bupropion hydrochloride are examples of a different class of antidepressants called SNRIs. The SNRIs should be used with caution in ESKD patients, since these drugs are primarily renally excreted. Bupropion has active metabolites that are almost completely removed by the kidney. These metabolites may accumulate in dialysis patients, predisposing them to developing seizures.

c. Monoamine oxidase inhibitors (MAOIs). MAOIs have numerous side effects and should be avoided if possible in ESKD patients, because of their potential to cause hypotension.

2. Nonpharmacologic options. There are several forms of psychotherapy (cognitive behavioral therapy [CBT], interpersonal, supportive, and group therapy) that might be effective in managing psychological distress. There are few data on such treatments in patients with chronic kidney disease. Individual psychotherapy (cognitive-behavioral, interpersonal, and supportive) is useful when the patient has identified that there is a problem and has accepted encouragement by the clinician to seek treatment. A recent randomized crossover trial of 65 hemodialysis patients showed significant improvements in depression scores as measured by the Beck Depression Inventory II (BDI II) and the Hamilton Depression Rating Scale in those patients who received CBT. With CBT, there was also an improvement in quality-of-life scores and a reduction in interdialytic weight gain. Denial is common and is a way of coping with uncomfortable thoughts or feelings related to being a “dialysis patient.” When a patient is noncompliant with treatment, denial might play a part in such behavior. Such patients may benefit from psychiatric interventions. However, these patients may resist treatment, as the implication is that “there is something wrong” with them. Motivating a patient to accept these forms of therapy may be difficult. Introducing therapy as a stress management approach to living with ESKD might be one approach to ease the patient into appropriate treatment. Supportive psychotherapy in conjunction with pharmacologic treatment is important for decreasing the rate of relapse. Group therapy may also have a positive impact. One uncontrolled study showed participation in group therapy sessions at the dialysis unit was associated with improved patient survival. Finally, electroconvulsive therapy may be used for patients with
severe refractory depression, provided that there are no contraindications.

II. DEMENTIA/DELIRIUM. Neurocognitive disorders are common in ESKD patients. Cognitive deficits may be related to underlying uremia or other coexistent underlying medical conditions, as described in more detail in Chapter 40

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