Official Title: “Maintenance Therapies in Late-Life Depression: MTLD III”

This study will determine the effectiveness of combining escitalopram, venlafaxine, or duloxetine with donepezil, a medication used in Alzheimer's disease, in improving memory, concentration, attention, and problem solving abilities, and reducing the risk of depressive relapse in older individuals with depression.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2009

The purpose of this research study is to learn if combining an antidepressant medication (escitalopram, venlafaxine, or duloxetine) with a medication used in Alzheimer's Disease (donepezil), in elderly patients age 65 and older with major depression, will help to 1) improve and/or maintain memory, concentration, attention, and problem solving abilities such as ability to balance a checkbook, pay bills, use the telephone, and 2) reduce the risk of depressive symptoms from returning. Study participation will last up to two years.

We aim to investigate pharmacologic strategies for improving and stabilizing cognitive functioning in late-life depression and minimizing progression of cognitive and associated functional impairment. Cognitive impairment in late-life depression has not been adequately addressed in previous intervention research, is a core feature of the illness, contributes markedly to disability and impaired quality of life, and is an overlooked but potentially critical target of intervention. Data from the MTLD II study suggest that treating depression does not normalize cognitive functions and may not prevent their progression. We will test a pharmacologic strategy involving the cholinesterase inhibitor donepezil, in combination with maintenance antidepressant pharmacotherapy (escitalopram, venlafaxine, or duloxetine), to improve and to maintain cognitive functioning and functional competence in elderly patients with major depression.

We hypothesize that maintenance antidepressant pharmacotherapy combined with donepezil will be superior to maintenance antidepressant pharmacotherapy combined with placebo/clinical management in (1) improving cognitive performance; and (2) slowing progression of cognitive impairment and decline in functional competence. We plan to recruit 200 patients aged 65 and above in current episodes of major depression. Those who respond to antidepressant pharmacotherapy with citalopram, venlafaxine, or duloxetine will then be randomly assigned on a double-blind basis to one of two 24-month treatments:

1)antidepressant pharmacotherapy plus donepezil/clinical management; or 2)antidepressant pharmacotherapy plus placebo/clinical management.

For information on related studies, please follow these links:

http://clinicaltrials.gov/show/NCT00000377

http://clinicaltrials.gov/show/NCT00178100

Intervention(s) in this Clinical Trial

• Drug: Escitalopram, duloxetine, or venlafaxine plus donepezil
  • Dosage varies. Participant remains on an antidepressant throughout the study.
• Drug: Antidepressant medication plus placebo
  • Participant intially undergoes the same antidepressant treatment (escitalopram, venlafaxine, duloxetine) as the experimental group, but switches to placebo.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive treatment with antidepressants (escitalopram, venlafaxine, duloxetine) plus donepezil
• Placebo Comparator: 2
  • Participants will receive treatment with antidepressants (escitalopram, venlafaxine, duloxetine) plus placebo

Primary Measures

• Cognitive and functional performance measures: MATTIS Dementia Rating Scale, Folstein Mini-Mental, CDR, Apathy, EXIT, PASS, ISEL, SP-36, HAM-D, CIRS-G, NPI, McGill Pain Questionnaire, BSI, UKU, QWB, SCID
  • Time Frame: Measured at Month 3 and Years 1 and 2 in maintenance
    Safety Issue?: No

Secondary Measures

• Clinical measures: HRSD, Suicide Ideation Scale, UKU, PASS, SF-36, ISEL, NPI, McGill Pain Questionnaire, CIRS-G
  • Time Frame: Measured at each study visit
    Safety Issue?: No
• Functional status: PASS, Keitel Function Test; Late-Life Function and Disability Instrument, QWB
  • Time Frame: Measured at baseline, entry into maintenance, and Month 3 and Years 1 and 2 in maintenance
    Safety Issue?: No
• MRI, Antidepressant Treatment History Form
  • Time Frame: Measured once
    Safety Issue?: Yes

Inclusion Criteria:

• Current episode of major depression
• HRS-D 17-item score of 15 or higher
• Must be able to speak English
• Willing to discontinue other psychotropics
• Availability of family member/caregiver
• Hearing capacity adequate to respond to raised conversational voice
• Must have no formal diagnosis of dementia

Exclusion Criteria:

• Meets DSM-IV criteria for bipolar disorder, schizophrenia, schizoaffective disorder, or a psychotic disorders
• Alcohol/drug abuse within 12 months of study entry
• History of treatment non-adherence in other clinic protocols
• History of non-response to citalopram in other clinic protocols
• History of non-tolerance to SSRI therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 65 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Bruce G. Pollock, MD, PhD Principal Investigator University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00177671

Study ID Number: R01 MH043832-03

ClinicalTrials.gov Identifier: NCT00177671

Health Authority: United States: Federal Government

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