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Antidepressant Medication Plus Donepezil for Treating Late-life Depression

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ClinicalTrials.gov Identifier: NCT00177671
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : June 8, 2011
Last Update Posted : February 6, 2013
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Depression
Dementia
Interventions Drug: Escitalopram
Drug: Donepezil
Drug: Venlafaxine
Drug: Placebo
Drug: Duloxetine
Enrollment 220
Recruitment Details 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.
Pre-assignment Details 28 enrolled participants were not randomized due to the following reasons: dementia (19), consent withdrawal (4), con-compliance with research procedures (3), supervening medical problems that precluded participation (2).
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily) Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Period Title: Overall Study
Started 67 63
Month 12 45 57
Month 24 42 49
Completed 42 49
Not Completed 25 14
Reason Not Completed
Withdrawal by Subject             5             6
medical complications             2             0
Adverse Event             6             0
Physician Decision             12             8
Arm/Group Title Donepezil Placebo Total
Hide Arm/Group Description Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily) Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo Total of all reporting groups
Overall Number of Baseline Participants 67 63 130
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 63 participants 130 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
67
 100.0%
63
 100.0%
130
 100.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 63 participants 130 participants
73.1  (6.5) 73.9  (5.8) 73.5  (6.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 63 participants 130 participants
Female
49
  73.1%
51
  81.0%
100
  76.9%
Male
18
  26.9%
12
  19.0%
30
  23.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 67 participants 63 participants 130 participants
67 63 130
1.Primary Outcome
Title Global Cognitive Performance
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Number of Participants Analyzed 67 63
Mean (Standard Deviation)
Unit of Measure: Z-score
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)
2.Primary Outcome
Title Cognitive Instrumental Activities of Daily Living (IADL)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Some participants refused this testing.
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Number of Participants Analyzed 33 34
Measure Type: Number
Unit of Measure: Percentage of participants
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
3.Primary Outcome
Title Number of Participants With Recurrence of Major Depression
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Number of Participants Analyzed 67 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
19
(16 to 31)
11
(6 to 18)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil, Placebo
Comments We followed the intention to treat principle. We used Kaplan-Meier curves to quantify the percentage of participants who were free of depression recurrence over time. Cox proportional hazard models quantified hazard ratios comparing the 2 treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .05
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.97
Confidence Interval (2-Sided) 95%
1.00 to 4.41
Parameter Dispersion
Type: Standard Deviation
Value: 2.09
Estimation Comments [Not Specified]
4.Post-Hoc Outcome
Title Percentage of Participants With Mild Cognitive Impairment Converting to Dementia.
Hide Description 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.
Time Frame 2 year
Hide Outcome Measure Data
Hide Analysis Population Description
This is the percent of participants with mild cognitive impairment (MCI) in each arm of the study.
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description:
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)
Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Number of Participants Analyzed 30 27
Measure Type: Number
Unit of Measure: Percent of Participants
10 33
Time Frame 2 years
Adverse Event Reporting Description We determined adverse events by structured clinical interview.
 
Arm/Group Title Donepezil Placebo
Hide Arm/Group Description Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily) Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
All-Cause Mortality
Donepezil Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Donepezil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/67 (4.48%)      1/63 (1.59%)    
Cardiac disorders     
Myocardial infarcation with congestive heart failure  1  1/67 (1.49%)  1 0/63 (0.00%)  0
Death due to heart attack in person with history of coronary heart disease and hypertension.  1  0/67 (0.00%)  0 1/63 (1.59%)  1
Nervous system disorders     
stroke  1  1/67 (1.49%)  1 0/63 (0.00%)  0
Psychiatric disorders     
Suicide Attempt  1  1/67 (1.49%)  1 0/63 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, standard terminology
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Donepezil Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/67 (0.00%)      0/63 (0.00%)    
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).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Charles F. Reynolds III, MD
Organization: University of Pittsburgh
Phone: 412-246-6414
EMail: reynoldscf@upmc.edu
Layout table for additonal information
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 Submitted: September 13, 2005
First Posted: September 15, 2005
Results First Submitted: February 18, 2011
Results First Posted: June 8, 2011
Last Update Posted: February 6, 2013