Literature

Issue 1, April-June 2015, Literature Review

Psychosocial Intervention Improves Depression, Quality of Life, and Fluid Adherence in Hemodialysis
Pubmed ID: 24115478

Depression is a common yet frequently overlooked condition impacting a significant proportion of end stage renal disease (ESRD) patients. Depressive affect is a modifiable risk factor for increased morbidity and mortality among ESRD patients. There is a paucity of randomized controlled trials to evaluate interventions that may decrease rates of depression among patients with chronic kidney disease.

Cukor et al1 studied the impact of cognitive behavioral therapy (CBT) on patients with ESRD treated with hemodialysis (HD). 59 patients on HD from 2 New York City hemodialysis units were randomized to CBT (n=33) or a wait list control group (n=26). The patients in the CBT group had significant reductions in depressive affect scores as measured by the Beck Depression Inventory II and Hamilton Depression Rating Scale. Almost 90% of the HD patients who received CBT had resolution of their depression symptoms following therapy. The patients who received CBT also had improvements in quality of life scores and a reduction in inter-dialytic weight gains.

Our intervention builds on the experience of Cukor and colleagues to compare the impact of CBT vs. sertraline on depressive symptoms in patients with ESRD.

1 Cukor D, Halen NV, Asher DR, Coplan JD, Weedon J, Wyka KE, Saggi SJ, Kimmel PL. Psychosocial intervention improves depression, quality of Life, and fluid adherence in hemodialysis. J Am Soc Nephrol 25: 196-206, 2014

Issue 2, July-September 2015, Literature Review

Depressive Affect and Hospitalization Risk in Incident Hemodialysis Patients
Pubmed ID 25278546

Depression is an important, yet overlooked, 'modifiable risk factor' for adverse outcomes in patients with end stage renal disease on hemodialysis. Lacson et al1 recently evaluated 8776 patients new to hemodialysis in the Fresenius Database for 'depressive affect' (low mood), using Medical Outcomes Study 'Short Form 36 Survey (SF-36)'. 41% of these incident hemodialysis patients (tracked over one year) were found to have "high" depressive affect scores. Depression was assessed based on 2 questions:

   1. Have you felt so down I the dumps that nothing could cheer you up?
   2. Have you felt downhearted and blue?

Patients rated their level of depression on a scale from 1 ('all of the time') to 6 ('none of the time').

Hospitalization rates and hospital length of stay was assessed for one year after completion of the SF-36 survey in these patients. It was found that patients with higher depressive affect scores had:

   • Significantly higher rates of hospitalization,
   • Shorter time to initial hospitalization, and
   • Increased hospital lengths of stay.

The results of this study support our effort to evaluate the impact of a randomized controlled intervention to treat depression in the hemodialysis patient population. Treatment of depression may lead to improved outcomes for end stage renal disease patients including increased survival and decreased hospitalization rates.

1Lacson E Jr, Bruce L, Li NC, Mooney A, Maddux FW. Depressive affect and hospitalization risk in incident hemodialysis patients. Clin J Am Soc Nephrol 9: 1713-1719, 2014

Issue 3, October-December 2015, Literature Review

Associations of Depressive Symptoms and Pain with Dialysis Adherence, Health Resource Utilization, and Mortality in Patients Receiving Chronic Hemodialysis
Pubmed ID: 25081360

Weisbord et al1 evaluated the effect of depressive symptoms and perception of pain on adherence with dialysis regimen, use of healthcare resources and probability of death in patients treated with hemodialysis. The study analyzed data from 286 hemodialysis patients enrolled in the Symptom Management Involving End-Stage Renal Disease (SMILE) trial conducted between 2009 and 2011. Depressive symptoms and pain were assessed at multiple time points using the Patient Health Questionnaire 9 (PHQ-9) and Short-Form McGill Pain Questionnaire (SF-MPQ). As in previous studies, approximately 25% of patients reported moderate to severe depression at baseline and almost 50% of all patients experienced moderate to severe depression at least at one point in time during the course of the study. Patients with depressive symptoms were less likely to adhere to dialysis prescription, were hospitalized more often, and a higher risk for death. The perception of severe pain was also associated with these outcomes however there was no link with higher death risk. The authors conclude that while there is 'no evidence at present that treating depressive symptoms or pain decrease health care resource utilization or mortality, treatment can alleviate these bothersome symptoms'. The results of this significant study support our efforts to undertake a randomized controlled trial to assess the effect of anti-depressant medications versus cognitive behavioral therapy on the treatment of depression in hemodialysis patients. The study will test the effect of different approaches of treatment on a wide range of patient-reported outcomes. It is our hope that the results of this study will inform future interventional trials to see if treatment of depressive symptoms reduces hospitalizations and risk for death among patients undergoing hemodialysis.

1Weisbord SD, Mor MK, Sevick MA, et al. Associations of Depressive Symptoms and Pain with Dialysis Adherence, Health Resource Utilization, and Mortality in Patients Receiving Chronic Hemodialysis. Clin J Am Soc Nephrol 9: 1594-1602, 2014

Issue 4, January-March 2016, Literature Review

A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomized controlled trial of drug treatment for depression in patients undergoing hemodialysis
Pubmed ID: 26503099

Many patients undergoing dialysis suffer from depression. Even though it is so common, there are very few high-quality studies that have evaluated if it can be effectively treated and if so, how. ASCEND, the trial we are doing, is one such study. However, it is gratifying to note that there are other studies that are also looking at different treatment options for depression. Friedli et al1 plan to conduct a study to evaluate the feasibility of a randomized controlled clinical trial of using sertraline versus placebo in hemodialysis patients who meet the formal criteria for Major Depressive Disorder (MDD). The study will be conducted in four dialysis facilities in the United Kingdom. The study has two phases - a screening phase and a trial phase. Patients will be screened using a depression questionnaire, the BDI-II, the same as is being used in ASCEND. The patients with scores suggesting depressive symptoms will then be referred to a psychiatrist for a diagnostic interview. Patients diagnosed with MDD will then enter the trial phase where they will be randomized to either sertraline initial dose of 50 mg versus placebo for a duration of six months. This clinical trial will no doubt complement our study which compares the impact of sertraline and cognitive behavioral therapy in hemodialysis patients with depression. We eagerly await the results of this important trial.

1Friedli K, Almond M, Day C, et al. A study of sertraline in dialysis (ASSertID): a protocol for a pilot randomized controlled trial of drug treatment for depression in patients undergoing hemodialysis. BMC Nephrol 16: 172, 2015

Issue 5, April-June 2016, Literature Review

Clinical Practice Guidelines for treatment of depression
Pubmed ID: 26857948

Clinical Practice Guidelines for the treatment of adults with major depressive disorder have recently been published by the American College of Physicians1. The guideline was based on a systematic review of randomized controlled trials of patients with major depressive disorder from 1990-2015. The review evaluated the impact of psychotherapy, complementary and alternative medicine, cognitive behavioral therapy, exercise, and second generation anti-depressant therapy. For the majority of studies reviewed, there was no difference in the effect of using antidepressant medication versus nonpharmacologic approaches such as cognitive behavioral therapy. The ACP concluded that cognitive behavioral therapy or antidepressant treatment can be used to treat patients with major depressive disorder after thorough discussion of the risks and benefits with the patient. This ACP guideline underlines the importance of our randomized controlled trial to compare the effect of cognitive behavioral therapy versus sertraline for the treatment of major depressive disorder in patients on hemodialysis. The results of our randomized controlled trial have the potential to change clinical practice guidelines which currently report equivalence between the various treatment options for depression.

1Qaseem A, Barry MJ, Kansagara D. Nonpharmacologic versus pharmacologic treatment of adults patients with major depressive disorder: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine, 2016

Issue 6, July-September 2016, Literature Review

A randomized clinical trial (MOOD-HF): treating depression amongst those with congestive heart failure
Pubmed ID: 27367876

Weisbord et al1 There is limited data evaluating the impact of treating depression in patients that have other long-standing medical conditions; this is the rationale for the ongoing clinical trial, ASCEND, to determine the benefits in patients with end-stage renal disease. The MOOD-HF1 is a clinical trial that was recently completed for patients with another chronic condition, congestive heart failure. This randomized controlled clinical trial was designed to determine if 2 years of treatment with escitalopram, a drug like sertraline that is being used in ASCEND, improves morbidity, mortality, and mood in patients diagnosed with congestive heart failure and depression. Patients were screened for depression based on the Patient Health Questionnaire (PHQ-9) and the diagnosis was confirmed with the use of Structured Clinical Interview. Patients with depression were randomized to escitalopram 10-20 mg daily or placebo. Primary outcomes included death or hospitalization from any cause. Secondary outcomes included patient safety and severity of depression at 12 weeks of therapy as measured by the Montgomery-Asberg Depression Rating Scale. 12-week treatment with escitalopram had no significant effect on the severity of depression, risk for death or hospitalization.

While our group is studying a different patient population, congestive heart failure and end stage renal disease are both chronic medical conditions with significant morbidity and mortality. The MOOD-HF randomized controlled trial did not show benefit with treatment of depression with anti-depressant drugs compared to placebo in patients with heart failure. It remains to be determined whether the benefit from anti-depressant drugs, if any, is different from that with cognitive behavioral therapy on depressive symptoms in patients undergoing dialysis. ASCEND will fill this gap in our knowledge and we eagerly await the completion of the study.

1Angermann CE, Gelbrich G, Stork S, et al. Effect of escitalopram on all-cause mortality and hospitalization in patients with heart failure and depression. The MOOD-HF Randomized Clinical Trial. JAMA 315: 2683-2693, 2016