Identifying and Treating Depression in Hemodialysis Patients

NCT ID: NCT03390933

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2023-02-28

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.

Conditions

Depression; Hemodialysis-Induced Symptom

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fluoxetine Group

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

Group Type: EXPERIMENTAL

Fluoxetine

Intervention Type: DRUG

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.

Interventions

Fluoxetine

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.

Intervention Type: DRUG

Other Intervention Names

Prozac

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MetroHealth Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ash Sehgal

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ash Seghal, MD

Role: PRINCIPAL_INVESTIGATOR

MetroHealth Medical Center

Locations

MetroHealth Medical Center

Cleveland, Ohio, United States

Countries

United States

References

Cohen SD, Norris L, Acquaviva K, Peterson RA, Kimmel PL. Screening, diagnosis, and treatment of depression in patients with end-stage renal disease. Clin J Am Soc Nephrol. 2007 Nov;2(6):1332-42. doi: 10.2215/CJN.03951106. Epub 2007 Oct 17.

Reference Type: BACKGROUND

PMID: 17942763 (View on PubMed)

Hedayati SS, Bosworth HB, Kuchibhatla M, Kimmel PL, Szczech LA. The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients. Kidney Int. 2006 May;69(9):1662-8. doi: 10.1038/sj.ki.5000308.

Reference Type: BACKGROUND

PMID: 16598203 (View on PubMed)

Watnick S, Wang PL, Demadura T, Ganzini L. Validation of 2 depression screening tools in dialysis patients. Am J Kidney Dis. 2005 Nov;46(5):919-24. doi: 10.1053/j.ajkd.2005.08.006.

Reference Type: BACKGROUND

PMID: 16253733 (View on PubMed)

Cohen SD, Kimmel PL. Nutritional status, psychological issues and survival in hemodialysis patients. Contrib Nephrol. 2007;155:1-17. doi: 10.1159/000100952.

Reference Type: BACKGROUND

PMID: 17369709 (View on PubMed)

Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz I, Veis JH. Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients. Kidney Int. 2000 May;57(5):2093-8. doi: 10.1046/j.1523-1755.2000.00059.x.

Reference Type: BACKGROUND

PMID: 10792629 (View on PubMed)

Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Boyle DH, Verme D, Umana WO, Veis JH, Alleyne S, Cruz I. Behavioral compliance with dialysis prescription in hemodialysis patients. J Am Soc Nephrol. 1995 Apr;5(10):1826-34. doi: 10.1681/ASN.V5101826.

Reference Type: BACKGROUND

PMID: 7787151 (View on PubMed)

Lacson E Jr, Bruce L, Li NC, Mooney A, Maddux FW. Depressive affect and hospitalization risk in incident hemodialysis patients. Clin J Am Soc Nephrol. 2014 Oct 7;9(10):1713-9. doi: 10.2215/CJN.01340214. Epub 2014 Oct 2.

Reference Type: BACKGROUND

PMID: 25278546 (View on PubMed)

Lopes AA, Albert JM, Young EW, Satayathum S, Pisoni RL, Andreucci VE, Mapes DL, Mason NA, Fukuhara S, Wikstrom B, Saito A, Port FK. Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS. Kidney Int. 2004 Nov;66(5):2047-53. doi: 10.1111/j.1523-1755.2004.00977.x.

Reference Type: BACKGROUND

PMID: 15496178 (View on PubMed)

Chiu YW, Teitelbaum I, Misra M, de Leon EM, Adzize T, Mehrotra R. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin J Am Soc Nephrol. 2009 Jun;4(6):1089-96. doi: 10.2215/CJN.00290109. Epub 2009 May 7.

Reference Type: BACKGROUND

PMID: 19423571 (View on PubMed)

Kauffman KM, Dolata J, Figueroa M, Gunzler D, Huml A, Pencak J, Sajatovic M, Sehgal AR. Directly Observed Weekly Fluoxetine for Major Depressive Disorder Among Hemodialysis Patients: A Single-Arm Feasibility Trial. Kidney Med. 2022 Jan 17;4(3):100413. doi: 10.1016/j.xkme.2022.100413. eCollection 2022 Mar.

Reference Type: DERIVED

PMID: 35386606 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

IRB17-00768

Identifier Type: -

Identifier Source: org_study_id