Quality of Life and Depression in CKD: Improving Hope and Health Related Articles, pp. 424 and 433
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ife on dialysis is difficult. Dialysis patients are burdened with a part-time job they never applied for and cannot quit unless they undergo transplantation or withdraw from care. Their income from this “profession” is nil at best. In comparison to healthier counterparts, they carry a 5- to 500-fold greater risk of death, cannot eat what they please, can take pleasure trips only with extensive advanced planning, have a poor sex life, and must work all major holidays except Thanksgiving and Christmas.1,2 It is no wonder that the quality of life on dialysis therapy is poor and depression rates are high.3,4 In comparison, one might hypothesize a much brighter outlook for patients with chronic kidney disease (CKD) who are not burdened with the job of dialysis therapy. However, they also are treated to colorless diets, complementary comorbid conditions, curtailed life spans, and clear socioeconomic disadvantage versus the general population.5,6 Previously unaware of their relatively silent affliction, many are surprised to find that their kidney function is less than half of what is considered normal. Nonetheless, these patients have not been well known to experience high rates of depression or lack of quality in their lives because few descriptive data previously existed. In this issue of the American Journal of Kidney Diseases, Hedayati et al7 offer new insights in the area of depression, a major component in quality-of-life assessment, in non–dialysis-dependent patients with CKD. The article beginning on page 433 validates simple instruments to assess depression in veterans with CKD against goldstandard tools.7 The article beginning on page 424 determines the prevalence of major depression in patients with CKD and describes factors associated with major depression in this population.8 Thus, these articles establish trunks from which fruitful branches of further understanding can grow. Interestingly, the first known medical use of the term “quality of life” originated in a 1966 article about patients on maintenance dialysis therapy. The procedure was life saving, but the investigators questioned whether the patient’s quality of life was acceptable.9,10 The accompa-
nying editorial mentioned that quality of life is difficult to define. They borrow Sir Francis Bacon’s definition, which is “the harmony within a man, and between a man and world”11; the quantification of such harmony poses measurement difficulties.10 More than 40 years later, our profession still struggles with the challenges created when trying to generate hypotheses regarding quality of life and depression as a cause or result of an intervention. Even the current definition of health-related quality of life put forth by the World Health Organization (“A complete state of physical, mental, and social well-being and not merely the absence of disease and infirmity”12) is difficult to translate into readily measured entities (ie, metrics of depression). Tools to assess factors impacting on corollaries of quality of life, such as depression, have since been used and validated, primarily in dialysis patients. Early assessments in the late 1960s and early 1970s showed rates of depression of 0% to 100%, questioning the true validity of the instruments available at the time.3,13-15 Since then, many other instruments have been used. Rates of depressive disorder are as high as 26% to 29% in recent cohorts of patients with CKD, with rates of major depressive disorder ranging from 17% to 19% in comparison to 4% to 6% in the general and 6% to 10% in primary care clinic populations.7,16 Major depression is defined as lasting for 2 weeks or more, during which time patients experience anhedonia or depressed mood and at least 5 of the 9 Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria symptom domains, which include weight loss, sleep disturbances, psychomotor abnormalities, fatigue, feelings of worthlessness or guilt, inability to concentrate, and thoughts of death. These symptoms are not supposed to be attributable to a general medical condition, which Address correspondence to Suzanne Watnick, MD, Oregon Health and Science University, Portland Veterans Affairs Medical Center, Portland, OR. E-mail: watnicks@ ohsu.edu Published by Elsevier Inc on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. 0272-6386/09/5403-0002$0.00/0 doi:10.1053/j.ajkd.2009.06.009
American Journal of Kidney Diseases, Vol 54, No 3 (September), 2009: pp 399-402
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Suzanne Watnick Box 1. Components of the Quick Inventory of Depressive Symptomatology (Self Report)
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
Falling asleep Sleeping during the night Waking up too early Sleeping too much Feeling sad Decreased appetite Increased appetite Decreased weight Increased weight Concentration/decision making View of self Thoughts of death or suicide General interest Energy level Feeling slowed down Feeling restless
Note: The 16 questions are self-reported on a scale of 0 to 3 based on the past 7 days, with higher scores indicating greater severity of symptoms. Reproduced with permission.18
makes the diagnosis very difficult in patients with CKD.17 Not everyone with CKD is depressed; thus, robust screening tools are essential to focus resources. Hedayati’s group validates 2 of these screening tools against gold-standard criteria in the nondialysis CKD population: the Quick Inventory of Depressive Symptomatology and SelfReport (QIDS-SR16) and Beck Depression Inventory (BDI).18,19 The Patient Health Questionnaire, which has been validated in dialysis patients, also has been used in patients with non–dialysisdependent CKD16,20 (Boxes 1 and 2). Using the QIDS-SR16 and BDI alongside gold-standard assessments for depression, Hedayati et al7 report the incidence of major depressive disorder to be 21% in this population, although there was no control group. Others looking at rates of depressive symptoms in the CKD population have shown rates similar to either a general medical population22 or dialysis patients in their systems; however, gold-standard evaluations of depression were not included.20 Given this limitation, the relative contribution of nondialysis CKD to the diagnosis of major depression previously was unclear. The use of gold-standard assessments identified the relatively high prevalence of depression in Dr Hedayati’s target population; this moves the field forward by validating short easily administered instruments to assess depressive symptoms.
Depression in the CKD population is tightly correlated with poor quality of life,22,23 and it is an independent risk factor for a greater rate of illness and death in dialysis patients. However, research in the nondialysis CKD population, including the articles by Hedayati et al,7,8 is not longitudinally based and therefore is unable to draw such conclusions. Nonetheless, the article in this issue of AJKD shows that an association exists between depression and factors that may lead to poor outcomes, including diabetes, prior psychiatric illness, drug and alcohol use, and use of antidepressant medications.8 The biological rationale for poor outcomes with depressive symptoms is unclear. Depression results in abnormal hypothalamic-pituitary axis activity, with increased norepinephrine and cortisol secretion, which may have adverse consequences in a population with exorbitant rates of cardiovascular disease.24 Altered autonomic tone has been found in depressed patients after myocardial infarction.25 Additional abnormalities in serotonin levels lead to upregulation of platelet activation, with further potential for adverse cardiac events. The uremic milieu may cause a unique biological perturbation in patients with depression, with possible synergistic cardiac abnormalities. Uremia also may make patients more susceptible to mood disorders, but this is conjecture. The additional stressors faced by patients with CKD may both lead to depressive symptoms and hinder medical compliance, leading to worse care and outcomes.26 Research translating into improved care surrounding quality of life and depression is miniBox 2. Components of the Patient Health Questionnaire 1. 2. 3. 4. 5. 6. 7. 8.
Little interest or pleasure in doing things Feeling down, depressed, or hopeless Trouble falling or staying asleep or sleeping too much Feeling tired or having little energy Poor appetite or overeating Feeling bad about yourself Trouble concentrating on things Moving or speaking slowly or the opposite (restless or fidgety) 9. Thoughts that you would be better off dead or of hurting yourself Note: The 9 questions can be self-administered on a scale of 0 to 3 based on the past 2 weeks, with higher scores indicating greater severity of symptoms. Reproduced with permission.21
Editorial
mal, in part because of a paucity of outcome data for baseline issues.27 How this information translates to the 26 million non–dialysis-dependent patients with CKD in this country is unclear.28 Improvement in care is unlikely to occur until an entity is recognized, studied, and treated. In 1 group of patients initiating dialysis therapy with BDI scores of 15 or higher, only 16% were receiving therapy.29 In another group of dialysis patients, only half those offered treatment for depression accepted it.30 In prior large randomized controlled trials, such as the Sertaline Antidepressant Heart Attack Randomized Trial (SADHART), patients with kidney disease were excluded.31 Because our patients rarely are included in adequate trials of antidepressant therapy, we do not know the efficacy of treatment. Antidepressant trials of dialysis patients have had small sample sizes, lack of control groups, and inadequate followup. Side effects can compound symptoms and signs that our patients already experience. Central nervous system depression, increased bleeding risks, worsening nausea, sexual dysfunction, electrocardiogram abnormalities, and accumulation of toxic metabolites could be described in a brochure about either antidepressant side effects or advanced CKD. Other therapies, such as exercise and cognitive behavioral intervention, suggest a minimal positive effect.32,33 Sadly, as we wonder about improvement in outcomes after therapy for depression in patients with CKD, we remain blinded. The state of affairs regarding care for these patients, simply put, is depressing. Extensive guidelines have been established addressing many of the numbers that go awry for our patients with CKD. However, when a patient walks through the door of the dialysis unit or a provider’s office, the patient’s first thought is not whether he or she has met Kidney Disease Outcomes Quality Initiative guidelines. A first thought might be: How will I feel today? How is this impacting my life? This reminds us to consider such issues as depression and quality of life alongside the traditional guidelines. Our goal is the betterment of the lives of our patients, and depression as it impacts on quality of life clearly is a field that requires further exploration. Future studies must assess long-term outcomes in patients with CKD and depression so that we better understand the implication of such a diagnosis. Subsequently,
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randomized controlled trials need to address the efficacy and tolerability of therapy as it pertains to our patients. The articles by Hedayati et al7,8 are a first step toward the day when our patients can not only hope for, but also expect, treatments for their kidney disease that encompass their physical and mental well-being. Suzanne Watnick, MD Oregon Health and Science University Portland Veterans Affairs Medical Center Portland, Oregon
ACKNOWLEDGEMENTS Financial Disclosure: None.
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