Antidepressant Medication Plus Donepezil for Treating Late-life Depression

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00177671
First received: September 13, 2005
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Depression
Dementia
Drug: Escitalopram
Drug: Donepezil
Drug: Venlafaxine
Drug: Placebo
Drug: Duloxetine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Maintenance Therapies in Late-Life Depression: MTLD III

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Global Cognitive Performance [ Time Frame: Measured at baseline and Years 1 and 2 in maintenance ] [ Designated as safety issue: No ]
    Cognitive performance was assessed with 17 well established and validated individual tests measuring multiple domains. We transformed raw scores for individual tests into Z-scores using the baseline distribution of a non-depressed, cognitively normal, older adult comparison group (N=36)of similar age, education, and medical health recruited concurrently with the depressed participants. These Z-scores were averaged within each neuropsychological area to produce domain scores and then averaged over all 17 tests to calculate a global cognition performance score.

  • Cognitive Instrumental Activities of Daily Living (IADL) [ Time Frame: baseline, year 1 and year 2 ] [ Designated as safety issue: No ]
    The PASS (a performance-based assessment of instrumental activities of daily living)generates a composite measure of 13 cognitive IADL items capturing performance on activities such as shopping, bill paying, medication management, and home safety. We report the percentage of subjects at each assessment point adjudged to have independent functioning. This was determined by a clinician rater observing subjects perform each task and rating them according to predetermined criteria on a 4 point scale, ranging from 0 (unable) to 3 (independent).

  • Number of Participants With Recurrence of Major Depression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Recurrence of major depressive episodes as determined by SCID/DSM IV: two weeks of low mood and/or anhedonia, together with at least five of the following symptoms: suicidal ideation, low energy, sleep disturbance, appetite disturbance, psychic anxiety or somatic anxiety. In addition, a diagnosis of major depression requires evidence of distress or impairment.


Enrollment: 220
Study Start Date: December 2003
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

escitalopram plus donepezil (DNP)in the experimental maintenance phase of the study.

For subjects failing to respond to escitalopram during the initial open phase of acute treatment we allowed the use of duloxetine or venlafaxine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation donepezil.

Participants remained on the same antidepressant medication and dosage throughout the 2 year maintenance phase of the study. In the event of a recurrence of major depression during maintenance treatment, dosages of antidepressant medication were raised, or the antidepressant was switched to venlafaxine or duloxetine.

For subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of duloxetine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.

Drug: Escitalopram
Escitalopram, 10mg to 20mg daily.
Other Name: Lexapro
Drug: Donepezil
Donepezil, 5mg to 10mg daily.
Other Name: aricept
Drug: Venlafaxine
Venlafaxine, 150mg to 300mg daily.
Other Name: effexor XR
Drug: Duloxetine
Other Name: cymbalta
Placebo Comparator: 2

escitalopram plus placebo (PBO) in the experimental maintenance phase of the study.

For subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of duloxetine or venlafaxine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.

Participants remained on the same antidepressant medication and dosage throughout the 2 year maintenance phase of the study. In the event of a recurrence of major depression during maintenance treatment, dosages of antidepressant medication were raised, or the antidepressant was switched to venlafaxine or duloxetine.

For subjects failing to respond to escitalopram during the initial open phase of acute treatment, we allowed the use of venlafaxine or duloxetine to bring about remission and establish eligibility for randomized assignment to maintenance treatment with augmentation placebo.

Drug: Escitalopram
Escitalopram, 10mg to 20mg daily.
Other Name: Lexapro
Drug: Venlafaxine
Venlafaxine, 150mg to 300mg daily.
Other Name: effexor XR
Drug: Placebo
Other Name: placebo
Drug: Duloxetine
Other Name: cymbalta

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00177671

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Bruce G. Pollock, MD, PhD University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00177671     History of Changes
Other Study ID Numbers: R01 MH043832-03, R01MH043832, 0312018, DATR A4-GPS
Study First Received: September 13, 2005
Results First Received: February 18, 2011
Last Updated: January 31, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Pittsburgh:
Depression
Dementia
Alzheimer's Disease
Cognitive
Donepezil
Memory
Function
Elderly
Late-Life

Additional relevant MeSH terms:
Dementia
Depression
Depressive Disorder
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Behavioral Symptoms
Mood Disorders
Antidepressive Agents
Citalopram
Venlafaxine
Duloxetine
Dexetimide
Donepezil
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on August 19, 2014