Antidepressant Response in the Treatment of Depressive Symptoms and Frailty Characteristics in Older Adults

Sponsor
New York State Psychiatric Institute (Other)
Overall Status
Completed
CT.gov ID
NCT01973283
Collaborator
National Institute of Mental Health (NIMH) (NIH)
100
Enrollment
1
Location
1
Arm
81.5
Actual Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this open-administration treatment study of citalopram (or duloxetine) is to evaluate the effect of antidepressant medication on treating the syndrome of "frailty" in older adults with depressive symptoms. Patients with significant depressive symptoms (defined as CES-D (Center for Epidemiological Studies - Depression scale) > 10) and 1 or more symptoms of the frailty syndrome (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) will be evaluated and treated with citalopram (or duloxetine) for 8 weeks to test whether antidepressant medication improves both the syndrome of frailty and depressive symptoms. Patients evaluated at the Adult and Late Life Depression clinic and eligible to participate in the study will be treated with an antidepressant medication and assessed on the primary outcome variables (characteristics of frailty, depressive symptoms) as well as on secondary variables which include cognition (global cognition, episodic memory, executive function), and function (physical mobility, instrumental activities of daily living, and social functioning) prior to treatment initiation and following 8-weeks of treatment. The hypotheses for this protocol predict that we will discover a significant improvement on both frailty characteristics and depressive symptoms in this clinical population when treated with antidepressant medication (citalopram or duloxetine).

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Antidepressant Medication
Phase 4

Detailed Description

Frailty, "a syndrome of decreased resiliency and reserves", is defined by five characteristics: 1)"shrinking" (definition: unintentional weight loss of > 10 lbs in prior year, or > 5% loss of body weight in prior year at follow-up), 2) weakness (definition: grip strength in lowest 20% at baseline, adjusted for gender and BMI), 3) poor endurance/energy (definition: self-report of exhaustion on 2 items on the CES-D), 4) slowness (definition: slowest 20% on timed 4 meter or 15 foot walk, adjusted for gender and standing height), and 5) low physical activity (definition: weighted score of kilocalories expended per week as calculated from the Minnesota Leisure Time Activity questionnaire). Frailty is associated with poor prognosis including hospitalization, falls, worsening disability and mobility, and death.

Data from the Cardiovascular Health Study document the rate of comorbid depressive symptoms in frail older adults (16.2% of older adults with at least 1 frailty characteristic had a CES-D > 10, including 31% of older adults with 3 or more frailty characteristics, compared to 2.6% of nonfrail older adults) despite study exclusion of individuals who were taking an antidepressant (this is in part why we chose to include patients with a CES-D of > 10, rather than requiring a diagnosis of a depressive disorder such as major depression or dysthymia for this study). The relationship between frailty and depression however goes beyond this association; the five defining characteristics of frailty (exhaustion, decreased energy, weight loss, decreased grip strength, and slow/unsteady gait) overlap significantly with symptoms of geriatric depression (decreased energy and motivation, psychomotor slowing, weight loss, decreased participation in leisure activities).

The proposed study is innovative in that it is focuses on a group of older adults who have been unrepresented (via exclusion criteria) in previous clinical studies (frail older adults with comorbid depressive symptoms), and it treats the comorbid depressive symptoms and targets characteristics of the frailty syndrome in the hopes of altering the prognostic trajectory of this clinical sample. This protocol serves two purposes: 1. It tests the feasibility of recruiting and retaining frail older adults with depressive symptoms in a treatment trial, and 2. It provides pilot data for the effectiveness of an antidepressant medication on treating the characteristics of frailty and the comorbid depressive symptoms.

Study Design

Study Type:
Interventional
Actual Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Antidepressant Response in the Treatment of Depressive Symptoms and Frailty Characteristics in Older Adults
Actual Study Start Date :
Feb 19, 2014
Actual Primary Completion Date :
Dec 5, 2019
Actual Study Completion Date :
Dec 5, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Medication Treatment

Participants are treated with a flexible-dose antidepressant medication for a period of 8 weeks.

Drug: Antidepressant Medication
If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
Other Names:
  • Escitalopram
  • Duloxetine
  • Open treatment
  • Outcome Measures

    Primary Outcome Measures

    1. Hamilton Rating Scale for Depression (HRSD) [Week 8]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    2. Hamilton Rating Scale for Depression (HRSD) [6 Months]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    3. Hamilton Depression Rating Scale (HRSD) [12 Months]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    4. Hamilton Depression Rating Scale: Stratified by Baseline Frailty [Baseline (Week 0)]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    5. Hamilton Depression Rating Scale: Stratified by Baseline Frailty [Week 8]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    6. Hamilton Depression Rating Scale: Stratified by Baseline Frailty [Month 6]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    7. Hamilton Depression Rating Scale: Stratified by Baseline Frailty [Month 12]

      Measure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

    Secondary Outcome Measures

    1. World Health Organization Disability Assessment 2.0 (36-item) [Baseline (Week 0)]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    2. World Health Organization Disability Assessment 2.0 (36-item) [Week 8]

      Assesses the level of functioning of patients, a component of the frailty evaluation. Simple: the scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. This approach is practical to use as a hand-scoring approach and may be the method of choice in busy clinical settings or in paper-pencil interview situations. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    3. World Health Organization Disability Assessment 2.0 (36-item) [6 Months]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    4. World Health Organization Disability Assessment 2.0 (36-item) [12 Months]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    5. World Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty [Baseline (Week 0)]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    6. World Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty [Week 8]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    7. World Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty [Month 6]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    8. World Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty [Month 12]

      Assesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 95 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Anyone with 1 or more characteristics of frailty

    • HRSD>16 and a DSM-IV depressive disorder (e.g. MDD, Dysthymia)

    • Capable of providing informed consent

    • Currently followed by a PCP (had an eval in last 6-months)

    Exclusion Criteria:
    • Acute cancer treatment

    • Acute, severe or unstable medical illness

    • End stage medical illness (e.g. liver, kidney, pulmonary)

    • Mini Mental Exam < 24 or a diagnosis of dementia

    • Individuals who do not have capacity to consent

    • Diagnosis of substance abuse or dependence (last 12 months), excluding Nicotine dependence

    • History of psychosis or psychotic disorder or bipolar disorder

    • Patient is considered a significant risk of suicide

    • Subject is considered based on history to be unlikely to respond to the single agent antidepressant (i.e., subjects with treatment resistant depression, including subjects with previous treatment with ECT)

    • History of allergic or adverse reaction to escitalopram or duloxetine, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20 mg) or duloxetine (at least 4 weeks at dose of 90mg).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1New York State Psychiatric InstituteNew YorkNew YorkUnited States10032

    Sponsors and Collaborators

    • New York State Psychiatric Institute
    • National Institute of Mental Health (NIMH)

    Investigators

    • Principal Investigator: Patrick Brown, PhD, New York State Psychiatric Institute

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Patrick J. Brown, Associate Professor of Clinical Psychology (in Psychiatry), New York State Psychiatric Institute
    ClinicalTrials.gov Identifier:
    NCT01973283
    Other Study ID Numbers:
    • #6470/7289R
    • K23MH099097-01A1
    First Posted:
    Oct 31, 2013
    Last Update Posted:
    Jan 29, 2021
    Last Verified:
    Jan 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleMedication Treatment-8 Weeks
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Period Title: Overall Study
    STARTED100
    COMPLETED96
    NOT COMPLETED4

    Baseline Characteristics

    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Overall Participants100
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.56
    (7.59)
    Sex: Female, Male (Count of Participants)
    Female
    66
    66%
    Male
    34
    34%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    12
    12%
    Not Hispanic or Latino
    88
    88%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    17
    17%
    White
    68
    68%
    More than one race
    5
    5%
    Unknown or Not Reported
    10
    10%
    Region of Enrollment (Count of Participants)
    United States
    100
    100%
    Hamilton Rating Scale for Depression (HRSD) (Score on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Score on a scale]
    20.32
    (5.84)

    Outcome Measures

    1. Primary Outcome
    TitleHamilton Rating Scale for Depression (HRSD)
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time FrameWeek 8

    Outcome Measure Data

    Analysis Population Description
    Although 100 patients were assessed at baseline, 4 dropped out during the course of the 8-week trial. This leaves an analyzable sample of 96.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants96
    Mean (Standard Deviation) [score on a scale]
    13.3
    (7.90)
    2. Primary Outcome
    TitleHamilton Rating Scale for Depression (HRSD)
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time Frame6 Months

    Outcome Measure Data

    Analysis Population Description
    Of the initial 100 patients assessed at baseline, 29 participants chose to not continue treatment past 8-weeks. As such, only 71 continued into the 10-month continuation phase of the project. Although these 29 were slightly older than the 71 who continued, they did not differ from those who continued in any other way including depression severity at baseline or 8-week treatment response. Because these 29 opted out of treatment after 8-weeks, only 71 were able to be analyzed at 6-months.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants71
    Mean (Standard Deviation) [score on a scale]
    12.5
    (7.44)
    3. Primary Outcome
    TitleHamilton Depression Rating Scale (HRSD)
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time Frame12 Months

    Outcome Measure Data

    Analysis Population Description
    Of the 71 who continued with treatment past 8-weeks, 11 dropped out between the 6- and 12-month assessment points. As such, 60 patients underwent 12-month assessments and were analyzable at 12-months.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants60
    Mean (Standard Deviation) [score on a scale]
    13.6
    (7.48)
    4. Primary Outcome
    TitleHamilton Depression Rating Scale: Stratified by Baseline Frailty
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time FrameBaseline (Week 0)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants4951
    Mean (Standard Deviation) [score on a scale]
    21
    (6.61)
    19.7
    (5.73)
    5. Primary Outcome
    TitleHamilton Depression Rating Scale: Stratified by Baseline Frailty
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time FrameWeek 8

    Outcome Measure Data

    Analysis Population Description
    Although 100 patients were assessed at baseline, 4 dropped out during the course of the 8-week trial. This leaves an analyzable sample of 96.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants4848
    Mean (Standard Deviation) [score on a scale]
    15.1
    (8.23)
    11.6
    (7.21)
    6. Primary Outcome
    TitleHamilton Depression Rating Scale: Stratified by Baseline Frailty
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time FrameMonth 6

    Outcome Measure Data

    Analysis Population Description
    Of the initial 100 patients assessed at baseline, 29 participants chose to not continue treatment past 8-weeks. As such, only 71 continued into the 10-month continuation phase of the project. Although these 29 were slightly older than the 71 who continued, they did not differ from those who continued in any other way including depression severity at baseline or 8-week treatment response. Because these 29 opted out of treatment after 8-weeks, only 71 were able to be analyzed at 6-months.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants3140
    Mean (Standard Deviation) [score on a scale]
    14.8
    (8.65)
    10.8
    (5.85)
    7. Primary Outcome
    TitleHamilton Depression Rating Scale: Stratified by Baseline Frailty
    DescriptionMeasure Description: Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluating recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score above 16 is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.
    Time FrameMonth 12

    Outcome Measure Data

    Analysis Population Description
    Of the 71 who continued with treatment past 8-weeks, 11 dropped out between the 6- and 12-month assessment points. As such, 60 patients underwent 12-month assessments and were analyzable at 12-months.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants2733
    Mean (Standard Deviation) [score on a scale]
    14.3
    (8.21)
    13.0
    (6.91)
    8. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameBaseline (Week 0)

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 12 subjects completed the baseline WHODAS assessment, so only 12 subjects' data were included in the analysis.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants12
    Mean (Standard Deviation) [score on a scale]
    71.7
    (24.8)
    9. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. Simple: the scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. This approach is practical to use as a hand-scoring approach and may be the method of choice in busy clinical settings or in paper-pencil interview situations. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameWeek 8

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 84 subjects completed the Week 8 WHODAS assessment, so only 84 subjects' data were included in the analysis.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants84
    Mean (Standard Deviation) [score on a scale]
    68.7
    (21.6)
    10. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time Frame6 Months

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 64 subjects completed the Month 6 WHODAS assessment, so only 64 subjects' data were included in the analysis.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants64
    Mean (Standard Deviation) [score on a scale]
    66.7
    (20.9)
    11. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time Frame12 Months

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 59 subjects completed the Month 12 WHODAS assessment, so only 59 subjects' data were included in the analysis.
    Arm/Group TitleMedication Treatment
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    Measure Participants59
    Mean (Standard Deviation) [score on a scale]
    67.8
    (20.7)
    12. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameBaseline (Week 0)

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 12 subjects completed the baseline WHODAS assessment, so only 12 subjects' data were included in the analysis.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants75
    Mean (Standard Deviation) [score on a scale]
    82.3
    (24.1)
    56.8
    (18.8)
    13. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameWeek 8

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 84 subjects completed the Week 8 WHODAS assessment, so only 84 subjects' data were included in the analysis.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants4242
    Mean (Standard Deviation) [score on a scale]
    77.9
    (22.8)
    59.4
    (15.8)
    14. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameMonth 6

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 64 subjects completed the Month 6 WHODAS assessment, so only 64 subjects' data were included in the analysis.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants2935
    Mean (Standard Deviation) [score on a scale]
    77.2
    (19.9)
    58.0
    (17.5)
    15. Secondary Outcome
    TitleWorld Health Organization Disability Assessment 2.0 (36-item)--Stratified by Baseline Frailty
    DescriptionAssesses the level of functioning of patients, a component of the frailty evaluation. The scores assigned to each of the items: "none" (0), "mild" (1) "moderate" (2), "severe" (3), and "extreme" (4) - are summed. Each of the items is simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations. Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
    Time FrameMonth 12

    Outcome Measure Data

    Analysis Population Description
    Although 100 subjects enrolled in the study, only 59 subjects completed the Month 12 WHODAS assessment, so only 59 subjects' data were included in the analysis.
    Arm/Group TitleFrailNot/Intermediate Frail
    Arm/Group DescriptionParticipants who had 3 or more frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as having frailty.Participants who had 0-2 frailty characteristics (slow gait speed, weak grip strength, low physical activity levels, the presence of fatigue and significant weight loss, all determined using prespecified cut scores) at baseline are categorized as either non-frail (0 characteristics) or intermediate frailty (1-2 characteristics).
    Measure Participants2732
    Mean (Standard Deviation) [score on a scale]
    80.9
    (18.1)
    56.7
    (15.8)

    Adverse Events

    Time FrameAdverse Events were collected for 12 months
    Adverse Event Reporting Description
    Arm/Group TitleMedication Treatment-8 Weeks
    Arm/Group DescriptionParticipants are treated with a flexible-dose antidepressant medication for a period of 8 weeks. Antidepressant Medication: If patient has a history of non-response or cannot tolerate escitalopram and/or duloxetine, then they will be treated openly with an approved antidepressant.
    All Cause Mortality
    Medication Treatment-8 Weeks
    Affected / at Risk (%)# Events
    Total0/100 (0%)
    Serious Adverse Events
    Medication Treatment-8 Weeks
    Affected / at Risk (%)# Events
    Total2/100 (2%)
    Injury, poisoning and procedural complications
    Fall2/100 (2%) 2
    Other (Not Including Serious) Adverse Events
    Medication Treatment-8 Weeks
    Affected / at Risk (%)# Events
    Total0/100 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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

    Name/TitlePatrick J Brown
    OrganizationNew York State Psychiatric Institute
    Phone646-774-8666
    Emailpatrick.brown@nyspi.columbia.edu
    Responsible Party:
    Patrick J. Brown, Associate Professor of Clinical Psychology (in Psychiatry), New York State Psychiatric Institute
    ClinicalTrials.gov Identifier:
    NCT01973283
    Other Study ID Numbers:
    • #6470/7289R
    • K23MH099097-01A1
    First Posted:
    Oct 31, 2013
    Last Update Posted:
    Jan 29, 2021
    Last Verified:
    Jan 1, 2021