Antidepressant Medication Plus Donepezil for Treating Late-life Depression

NCT00177671 | Completed Phase 4 Results DMC

• 4 other identifiers: R01MH043832-03R01MH0438320312018DATR A4-GPS
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Dementia

Keywords

Depression; Dementia; Alzheimer's Disease; Cognitive; Donepezil; Memory; Function; Elderly; Late-Life

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Study Arms (2)

1

EXPERIMENTAL

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; Drug: Donepezil; Drug: Venlafaxine; Drug: Duloxetine

2

PLACEBO COMPARATOR

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; Drug: Venlafaxine; Drug: Placebo; Drug: Duloxetine

Interventions

Escitalopram DRUG

Escitalopram, 10mg to 20mg daily.

Also known as: Lexapro

1; 2

Donepezil DRUG

Donepezil, 5mg to 10mg daily.

Also known as: aricept

1

Venlafaxine DRUG

Venlafaxine, 150mg to 300mg daily.

Also known as: effexor XR

1; 2

Placebo DRUG

2

Duloxetine DRUG

Also known as: cymbalta

1; 2

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (5)

• 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.

  PMID: 21199965 BACKGROUND

• 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.

  PMID: 24290367 DERIVED

• 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.

  PMID: 24144505 DERIVED

• 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.

  PMID: 19210951 DERIVED

• 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.

  PMID: 18251622 DERIVED

MeSH Terms

Conditions

Depression; Dementia; Alzheimer Disease

Interventions

Escitalopram; Donepezil; Venlafaxine Hydrochloride; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperidines; Heterocyclic Compounds, 1-Ring; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Lipids; Thiophenes; Sulfur Compounds

Limitations and Caveats

Observations about dementia conversion rates were obtained from post hoc subgroup analyses of participants with mild cognitive impairment (N=57) and participants with normal cognition at time of randomization (N=63).

Results Point of Contact

• Title: Charles F. Reynolds III, MD
• Organization: University of Pittsburgh

reynoldscf@upmc.edu

412-246-6414

Study Officials

• Bruce G. Pollock, MD, PhD

  University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: December 1, 2003
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: February 6, 2013
• Results First Posted: June 8, 2011

Record last verified: 2013-01

Locations

US (1)