Identifying and Treating Depression in Hemodialysis Patients

Phase 4

Completed

Conditions: Depression
Hemodialysis-Induced Symptom

Interventions: Drug: Fluoxetine

Registration Number: NCT03390933

Lead Sponsor: MetroHealth Medical Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fluoxetine Group	Fluoxetine	Approximately 96 patients will be enrolled into the intervention (Phase II) over the duration of the entire study.

Primary Outcome Measures

Name	Time	Method
To Determine the Impact of Directly Observed Weekly Fluoxetine Treatment on Remission of Depression Among Hemodialysis Patients.	3 years	remission of depression, defined as a week 12 Patient Health Questionnaire 9 (PHQ-9) total score of \<5. The survey consists of 9 questions to gauge depression/depressive symptoms. Each question asks - Over the last 2 weeks, how often have you been bothered by any of the following problems: Each questions 0-3 scale (0=not at all 1= several days 2= more than half the days 3=nearly every day ). Range =0min to 27max. A TOTAL SCORE OF ≥10 IS AN ESTABLISHED THRESHOLD FOR CLINICALLY RELEVANT DEPRESSIVE SYMPTOMS. Less than 5 is total remission of depressive symptoms.

Secondary Outcome Measures