Trial Outcomes & Findings for Antidepressant Medication Plus Donepezil for Treating Late-life Depression (NCT NCT00177671)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

220 participants

Primary outcome timeframe

Measured at baseline and Years 1 and 2 in maintenance

Results posted on

2013-02-06

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	Donepezil Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Study STARTED	67	63
Overall Study Month 12	45	57
Overall Study Month 24	42	49
Overall Study COMPLETED	42	49
Overall Study NOT COMPLETED	25	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Overall Study Withdrawal by Subject	5	6
Overall Study medical complications	2	0
Overall Study Adverse Event	6	0
Overall Study Physician Decision	12	8

Baseline Characteristics

Antidepressant Medication Plus Donepezil for Treating Late-life Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil n=67 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=63 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	67 Participants n=5 Participants	63 Participants n=7 Participants	130 Participants n=5 Participants
Age Continuous	73.1 years STANDARD_DEVIATION 6.5 • n=5 Participants	73.9 years STANDARD_DEVIATION 5.8 • n=7 Participants	73.5 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	51 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment United States	67 participants n=5 Participants	63 participants n=7 Participants	130 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Donepezil n=67 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=63 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Global Cognitive Performance Baseline (N=67;N=63)	-0.47 Z-score Standard Deviation 0.88	-0.47 Z-score Standard Deviation 0.76
Global Cognitive Performance Year 1 (N=45; N=57)	-0.23 Z-score Standard Deviation 0.79	-0.65 Z-score Standard Deviation 0.81
Global Cognitive Performance Year 2 N=42; N=49)	-0.31 Z-score Standard Deviation 0.92	-0.56 Z-score Standard Deviation 0.90

PRIMARY outcome

Timeframe: baseline, year 1 and year 2

Population: Some participants refused this testing.

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).

Outcome measures

Outcome measures
Measure	Donepezil n=33 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=34 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Cognitive Instrumental Activities of Daily Living (IADL) Year 1 (N=23; N=25)	62.16 Percentage of participants	54.35 Percentage of participants
Cognitive Instrumental Activities of Daily Living (IADL) Baseline (N=33; N=34)	54.10 Percentage of participants	61.82 Percentage of participants
Cognitive Instrumental Activities of Daily Living (IADL) Year 2 (N=11; N=17)	36.67 Percentage of participants	47.22 Percentage of participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Donepezil n=67 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=63 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Number of Participants With Recurrence of Major Depression	19 participants Interval 16.0 to 31.0	11 participants Interval 6.0 to 18.0

POST_HOC outcome

Timeframe: 2 year

Population: This is the percent of participants with mild cognitive impairment (MCI) in each arm of the study.

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.

Outcome measures

Outcome measures
Measure	Donepezil n=30 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=27 Participants Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Percentage of Participants With Mild Cognitive Impairment Converting to Dementia.	10 Percent of Participants	33 Percent of Participants

Adverse Events

Donepezil

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Donepezil n=67 participants at risk Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus donepezil (5mg to 10mg daily)	Placebo n=63 participants at risk Treatment with antidepressants (escitalopram (10mg to 20mg daily), venlafaxine (150mg to 300mg daily), duloxetine(20mg to 120mg daily) plus placebo
Psychiatric disorders Suicide Attempt	1.5% 1/67 • Number of events 1 • 2 years We determined adverse events by structured clinical interview.	0.00% 0/63 • 2 years We determined adverse events by structured clinical interview.
Nervous system disorders stroke	1.5% 1/67 • Number of events 1 • 2 years We determined adverse events by structured clinical interview.	0.00% 0/63 • 2 years We determined adverse events by structured clinical interview.
Cardiac disorders Myocardial infarcation with congestive heart failure	1.5% 1/67 • Number of events 1 • 2 years We determined adverse events by structured clinical interview.	0.00% 0/63 • 2 years We determined adverse events by structured clinical interview.
Cardiac disorders Death due to heart attack in person with history of coronary heart disease and hypertension.	0.00% 0/67 • 2 years We determined adverse events by structured clinical interview.	1.6% 1/63 • Number of events 1 • 2 years We determined adverse events by structured clinical interview.

Other adverse events

Adverse event data not reported

Additional Information

Charles F. Reynolds III, MD

University of Pittsburgh

Phone: 412-246-6414

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place