Antidepressant Medication Plus Donepezil for Treating Late-life Depression
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| ClinicalTrials.gov Identifier: NCT00177671 |
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Recruitment Status :
Completed
First Posted : September 15, 2005
Results First Posted : June 8, 2011
Last Update Posted : February 6, 2013
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Depression Dementia | Drug: Escitalopram Drug: Donepezil Drug: Venlafaxine Drug: Placebo Drug: Duloxetine | Phase 4 |
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
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 220 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Maintenance Therapies in Late-Life Depression: MTLD III |
| Study Start Date : | December 2003 |
| Actual Primary Completion Date : | September 2009 |
| Actual Study Completion Date : | September 2009 |
| Arm | Intervention/treatment |
|---|---|
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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 |
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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 Drug: Duloxetine Other Name: cymbalta |
- Global Cognitive Performance [ Time Frame: Measured at baseline and Years 1 and 2 in maintenance ]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 ]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 ]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.
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| Ages Eligible for Study: | 65 Years and older (Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00177671
| United States, Pennsylvania | |
| University of Pittsburgh Medical Center | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Principal Investigator: | Bruce G. Pollock, MD, PhD | University of Pittsburgh Professor of Psychiatry, Pharmacology, and Nursing |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT00177671 |
| Other Study ID Numbers: |
R01MH043832-03 ( U.S. NIH Grant/Contract ) R01MH043832 ( U.S. NIH Grant/Contract ) 0312018 DATR A4-GPS |
| First Posted: | September 15, 2005 Key Record Dates |
| Results First Posted: | June 8, 2011 |
| Last Update Posted: | February 6, 2013 |
| Last Verified: | January 2013 |
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Depression Dementia Alzheimer's Disease Cognitive Donepezil |
Memory Function Elderly Late-Life |
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Dementia Depression Depressive Disorder Behavioral Symptoms Mood Disorders Mental Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Duloxetine Hydrochloride Donepezil Citalopram Venlafaxine Hydrochloride Serotonin Uptake Inhibitors |
Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents Psychotropic Drugs Peripheral Nervous System Agents Cholinergic Agents Serotonin and Noradrenaline Reuptake Inhibitors Analgesics Sensory System Agents Dopamine Agents |