A Phase 4 interventional study of Escitalopram and Donepezil in Depression and Dementia, sponsored by University of Pittsburgh. Completed at 1 site in United States. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2013-02-06.
Sponsored by University of Pittsburgh · Phase 4, Interventional, and Treatment
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.
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
2,172 studies on the registry are indexed under Dementia; 540 are open to participants now.
This study's enrollment of 220 is above the median of 83 across 1,629 interventional studies indexed under Dementia.
Browse Dementia studies →University of Pittsburgh is the lead sponsor of 1,385 studies on the registry; 167 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 4 (50%) have results posted.
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Exclusion Criteria:
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
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
Escitalopram, 10mg to 20mg daily.
Also known as: Lexapro
Donepezil, 5mg to 10mg daily.
Also known as: aricept
Venlafaxine, 150mg to 300mg daily.
Also known as: effexor XR
Also known as: cymbalta
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.
Time frame: 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).
Time frame: 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.
Time frame: 2 years
220 signed consent; 158 participants completed pre-randomization testing; 130 participants were randomized. Of these 130, 67 randomized to donepezil augmentation and 63 to placebo.
| Milestone | Donepezil | Placebo |
|---|---|---|
| Started | 67 | 63 |
| Month 12 | 45 | 57 |
| Month 24 | 42 | 49 |
| Completed | 42 | 49 |
| Not completed | 25 | 14 |
| Withdrew: Withdrawal by subject | 5 | 6 |
| Withdrew: Medical complications | 2 | 0 |
| Withdrew: Adverse event | 6 | 0 |
| Withdrew: Physician decision | 12 | 8 |
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.
| Z-score | Donepezil | Placebo |
|---|---|---|
| Baseline (N=67;N=63) | -0.47 ± 0.88 | -0.47 ± 0.76 |
| Year 1 (N=45; N=57) | -0.23 ± 0.79 | -0.65 ± 0.81 |
| Year 2 N=42; N=49) | -0.31 ± 0.92 | -0.56 ± 0.90 |
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).
| Percentage of participants | Donepezil | Placebo |
|---|---|---|
| Baseline (N=33; N=34) | 54.10 | 61.82 |
| Year 1 (N=23; N=25) | 62.16 | 54.35 |
| Year 2 (N=11; N=17) | 36.67 | 47.22 |
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.
| participants | Donepezil | Placebo |
|---|---|---|
| Number of Participants With Recurrence of Major Depression | 19 (16 to 31) | 11 (6 to 18) |
Conversion to dementia was ascertained by the University of Pittsburgh Alzheimer Disease Research Center (ADRC), using data on neuropsychological performance and IADL functioning, as well as other relevant clinical data. Diagnoses were made according to National Alzheimer Coordinating Center criteria.
| Percent of Participants | Donepezil | Placebo |
|---|---|---|
| Percentage of Participants With Mild Cognitive Impairment Converting to Dementia. | 10 | 33 |
Collected over 2 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Donepezil | — | 3/67 (4.5%) | 0/67 (0%) |
| Placebo | — | 1/63 (1.6%) | 0/63 (0%) |
| Event | Donepezil | Placebo |
|---|---|---|
| Death due to heart attack in person with history of coronary heart disease and hypertension.Cardiac disorders | 0/67 | 1/63 |
| Suicide AttemptPsychiatric disorders | 1/67 | 0/63 |
| strokeNervous system disorders | 1/67 | 0/63 |
| Myocardial infarcation with congestive heart failureCardiac disorders | 1/67 | 0/63 |
| Age, Categorical(Participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 67 | 63 | 130 |
| Age Continuous(years) | Donepezil | Placebo | Total |
|---|---|---|---|
| Mean | 73.1 ± 6.5 | 73.9 ± 5.8 | 73.5 ± 6.2 |
| Sex: Female, Male(Participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| Female | 49 | 51 | 100 |
| Male | 18 | 12 | 30 |
| Region of Enrollment(participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| United States | 67 | 63 | 130 |
This study is completed, as verified in Jan 2013. You cannot join it, but the record below documents what was studied.
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