Identifying and Treating Depression in Hemodialysis Patients

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.

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