Antidepressant Medication Plus Donepezil for Treating Late-life Depression

Depression Clinical Trial

Official title:

Maintenance Therapies in Late-Life Depression: MTLD III

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00177671
• Other study ID #: R01 MH043832-03
• Secondary ID: R01MH04383203120
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2005
• Last updated: January 31, 2013
• Start date: December 2003
• Est. completion date: September 2009

Study information

• Verified date: January 2013
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dementia
• Depression
• Depressive Disorder

Intervention

Drug:
• Escitalopram
Escitalopram, 10mg to 20mg daily.
• Donepezil
Donepezil, 5mg to 10mg daily.
• Venlafaxine
Venlafaxine, 150mg to 300mg daily.
• Placebo

• Duloxetine

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Cognitive Performance	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.	Measured at baseline and Years 1 and 2 in maintenance	No
Primary	Cognitive Instrumental Activities of Daily Living (IADL)	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).	baseline, year 1 and year 2	No
Primary	Number of Participants With Recurrence of Major Depression	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.	2 years	No