Clinical trial NCT00177671: Antidepressant Medication Plus Donepezil for Treating Late-life Depression
Official title: Maintenance Therapies in Late-Life Depression: MTLD III
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Dementia
Keywords: Depression
Dementia
Alzheimer's Disease
Cognitive
Donepezil
Memory
Function
Elderly
Late-Life
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-09-15
Enrollment: 220
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Global Cognitive Performance
timeFrame: Measured at baseline and Years 1 and 2 in maintenance
measure: Cognitive Instrumental Activities of Daily Living (IADL)
timeFrame: baseline, year 1 and year 2
measure: Number of Participants With Recurrence of Major Depression
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing
name: Bruce G. Pollock, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reynolds CF 3rd, Butters MA, Lopez O, Pollock BG, Dew MA, Mulsant BH, Lenze EJ, Holm M, Rogers JC, Mazumdar S, Houck PR, Begley A, Anderson S, Karp JF, Miller MD, Whyte EM, Stack J, Gildengers A, Szanto K, Bensasi S, Kaufer DI, Kamboh MI, DeKosky ST. Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Arch Gen Psychiatry. 2011 Jan;68(1):51-60. doi: 10.1001/archgenpsychiatry.2010.184.
citation: Diniz BS, Reynolds CF 3rd, Begley A, Dew MA, Anderson SJ, Lotrich F, Erickson KI, Lopez O, Aizenstein H, Sibille EL, Butters MA. Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. J Psychiatr Res. 2014 Feb;49:96-101. doi: 10.1016/j.jpsychires.2013.11.004. Epub 2013 Nov 20.
citation: Andreescu C, Tudorascu DL, Butters MA, Tamburo E, Patel M, Price J, Karp JF, Reynolds CF 3rd, Aizenstein H. Resting state functional connectivity and treatment response in late-life depression. Psychiatry Res. 2013 Dec 30;214(3):313-21. doi: 10.1016/j.pscychresns.2013.08.007. Epub 2013 Oct 18.
citation: Sheffrin M, Driscoll HC, Lenze EJ, Mulsant BH, Pollock BG, Miller MD, Butters MA, Dew MA, Reynolds CF 3rd. Pilot study of augmentation with aripiprazole for incomplete response in late-life depression: getting to remission. J Clin Psychiatry. 2009 Feb;70(2):208-13. doi: 10.4088/jcp.07m03805. Epub 2009 Feb 10.
citation: Karp JF, Whyte EM, Lenze EJ, Dew MA, Begley A, Miller MD, Reynolds CF 3rd. Rescue pharmacotherapy with duloxetine for selective serotonin reuptake inhibitor nonresponders in late-life depression: outcome and tolerability. J Clin Psychiatry. 2008 Mar;69(3):457-63. doi: 10.4088/jcp.v69n0317.