Identifying and Treating Depression in Hemodialysis Patients

Study Overview
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Brief Summary
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Depression is present in about 20-30% of hemodialysis patients and is associated with morbidity and mortality. However, depression is inadequately diagnosed and treated among dialysis patients. This is due in part to the overlap between depressive symptoms (e.g. appetite change, trouble sleeping, feeling tired) and symptoms related to persistent metabolic derangements in hemodialysis patients (e.g. nausea, nocturnal cramps, feeling washed out after treatment). The overlap between depressive symptoms and dialysis-related complications makes it difficult to diagnose and therefore to treat depression. In addition, prescription of antidepressant medication may increase an already high pill burden and result in poor adherence. Moreover, the evidence base to guide depression treatment among hemodialysis patients is limited. In the investigators' previous work, they developed methods to use latent variables and structural equation modeling to isolate depressive symptoms. Other investigators have demonstrated that directly observed treatment enhances the effectiveness of tuberculosis and HIV treatment. Investigators now propose a cross-sectional study (Phase 1) followed by a single-arm clinical trial (Phase 2) at 17 dialysis facilities. The cross-sectional study will involve assessments of depressive symptoms (using the PHQ-9 screening instrument) as well as dialysis-related complications, anxiety, and quality of life (Quality of Life Questionnaire) in about 1083 patients. Investigators will then use structural equation modeling to develop and validate a hemodialysis-specific PHQ-9 (hdPHQ-9) that will isolate depressive symptoms. The trial will involve 96 patients with confirmed depression who will be assigned to directly observed weekly antidepressant treatment with fluoxetine. The primary outcome of the trial will be remission of depression at 12 weeks. The trial results will also be used to compare the responsiveness of the PHQ-9 and the hdPHQ-9. Investigators anticipate that the hdPHQ-9 will be a valid and responsive instrument that will isolate depressive symptoms in hemodialysis patients and ultimately improve the screening and diagnosis of depression. Investigators also expect that directly observed weekly fluoxetine treatment will be an effective way to manage depression among hemodialysis patients.

Detailed Description
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Depression is present in about 20-30% of hemodialysis patients and is associated with morbidity and mortality. However, depression is inadequately diagnosed and treated among dialysis patients. This is due in part to the overlap between depressive symptoms (e.g. appetite change, trouble sleeping, feeling tired) and symptoms related to persistent metabolic derangements in hemodialysis patients (e.g. nausea, nocturnal cramps, feeling washed out after treatment). The overlap between depressive symptoms and dialysis complications makes it difficult to diagnose and therefore to treat depression. In addition, prescription of antidepressant medication may increase an already high pill burden and result in poor adherence. Moreover, the evidence base to guide depression treatment among hemodialysis patients is limited. In the investigators' previous work, they developed methods to use latent variables and structural equation modeling to isolate depressive symptoms. Other investigators have demonstrated that directly observed treatment enhances the effectiveness of tuberculosis and HIV treatment. Investigators now propose a cross-sectional study (Phase 1) followed by a single-arm clinical trial (Phase 2) at 17 dialysis facilities. The cross-sectional study will involve assessments of depressive symptoms (using the PHQ-9 screening instrument) as well as dialysis-related complications, anxiety, and quality of life (Quality of Life Questionnaire) in about 1083 patients. The investigators will then use structural equation modeling to develop and validate a hemodialysis-specific PHQ-9 (hdPHQ-9) that will isolate depressive symptoms. The trial will involve 96 patients with confirmed depression who will be assigned to directly observed weekly antidepressant treatment with fluoxetine. The primary outcome of the trial will be remission of depression at 12 weeks. The trial results will also be used to compare the responsiveness of the PHQ-9 and the hdPHQ-9. The investigators anticipate that the hdPHQ-9 will be a valid and responsive instrument that will isolate depressive symptoms from dialysis complications and ultimately improve the screening and diagnosis of depression. They also expect that directly observed weekly fluoxetine treatment will be an effective way to manage depression among hemodialysis patients. Innovative features of the proposed project include the use of latent variables to address overlap, administration of a long acting weekly antidepressant, and directly observed treatment. The project has the potential not only to improve the diagnosis and management of depression among hemodialysis patients but also to improve their morbidity and mortality. Furthermore, it may serve as a model for future studies to isolate symptoms among overlapping medical conditions. Aim A. To develop and validate a self-reported depression screening instrument that isolates depressive symptoms from hemodialysis-related complications. Hypothesis: A hemodialysis-specific PHQ-9 (hdPHQ-9) will isolate depressive symptoms from dialysis complications. Aim B. To determine the impact of directly observed weekly fluoxetine treatment on remission of depression among hemodialysis patients. Hypothesis: About half of patients who have directly observed fluoxetine treatment will have remission of depression. Aim C. To examine the responsiveness of the new depression screening instrument to depression treatment. Hypothesis: Fluoxetine treatment will be associated with larger improvements in hdPHQ-9 scores than in PHQ-9 scores.

Official Title
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Using Latent Variables and Directly Observed Treatment to Improve the Diagnosis and Management of Depression Among Hemodialysis Patients

Conditions
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Depression, Hemodialysis-Induced Symptom

Intervention / Treatment
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* Drug: Fluoxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: currently on hemodialysis at a CDC dialysis unit English speaking able to provide informed consent Exclusion Criteria: on hemodialysis for less than 3 months comorbid psychotic, bipolar, substance use dependence, Alzheimer's or dementia Not eligible for Phase II (intervention) if currently on antidepressant medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The cross-sectional study will involve assessments of depressive symptoms (PHQ-9) and quality of life for 1083 patients. These data will be used to address Aim A. The single arm trial will involve 96 patients with DSM5-confirmed depression.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluoxetine Group<br>Approximately 96 patients will be enrolled into the intervention (Phase II) over the duration of the entire study. | Drug: Fluoxetine<br>* Patients enrolled into Phase II will be prescribed 2 weeks of short-acting fluoxetine 20 mg and will be instructed to take the prescription daily for 2 weeks. Then patients will be prescribed 10 additional weeks of 90 mg (weekly) fluoxetine and will be observed taking it once weekly at the dialysis unit. At the end of the 12 week study period, participants will be provided 4 additional weeks of 90 mg fluoxetine in order to provide sufficient time to follow up with their primary care physician or nephrologist.<br>* Other names: Prozac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To develop and validate a self-reported depression screening instrument that isolates depressive symptoms from hemodialysis-related complications. | baseline scores on measures of depression (PHQ-9) baseline scores of dialysis complications (KDQOL) factor analysis of the nine PHQ-9 items structural equation modeling of overlap of depressive symptoms and dialysis complications | 5 years | 
| To determine the impact of directly observed weekly fluoxetine treatment on remission of depression among hemodialysis patients. | remission of depression, defined as a week 12 PHQ-9 score of <5 | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the responsiveness of the new depression screening instrument to depression treatment. | change in hdPHQ-9 scores (delta hdPHQf) | 5 years |