Duloxetine Treatment in Elderly With Dysthymia

Sponsor
New York State Psychiatric Institute (Other)
Overall Status
Completed
CT.gov ID
NCT01852383
Collaborator
Eli Lilly and Company (Industry)
30
1
1
85.9
0.3

Study Details

Study Description

Brief Summary

Dysthymic disorder (DD) denotes chronic depression with fewer symptoms than major depressive disorder (MDD), and it affects ~ 2-4 % of adults with a similar prevalence in the elderly. In the elderly, dysthymic disorder (DD) has been shown to be associated with suffering and disability. The differences between young adult and elderly DD patients indicate that findings obtained in young adults with DD cannot be extrapolated to elderly DD patients who need to be studied separately. Data from epidemiologic studies support this view. In contrast to the data in young adult DD patients, there is a paucity of controlled data on the treatment of elderly DD patients. In our center, a double-masked, placebo-controlled study of 91 elderly DD patients did not find significant superiority for fluoxetine over placebo with response rates of 27.3% for fluoxetine and 19.6% for placebo in intent-to-treat analyses, and response rates of 37.5% for fluoxetine and 23.1% for placebo in completer analyses. Given the relative failure of selective serotonin reuptake inhibitor (SSRIs) to treat geriatric DD effectively, the investigators decided to evaluate the dual reuptake inhibitor, venlafaxine.

The investigators earlier completed an investigator-initiated, open-label 12-week venlafaxine (Effexor XR) trial. Of 23 elderly DD patients, 18 completed the trial. Fourteen (60.9%) were responders in intent-to-treat analyses with the last observation carried forward, and 77.8% were responders in completer analyses. Nearly half the sample (47.8%) met criteria for remission. In the intent-to-treat sample, increased severity of depression at baseline was associated with superior response and the presence of cardiovascular disease was associated with poorer response. These results with venlafaxine indicate that further treatment studies of dual serotonin-norepinephrine reuptake inhibitors like duloxetine are warranted in elderly patients with dysthymic disorder.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

HYPOTHESES:
  1. Duloxetine will reduce depressive symptomatology over a period of 12 weeks in elderly DD patients.

  2. Duloxetine-treated dysthymic patients will have significant improvement in measures of overall functioning.

This pilot trial enrolled 30 patients ≥ 60 years old with dysthymic disorder. Patients were recruited by clinician referral and by radio or newspaper advertisements that offered free evaluation by experienced clinicians for participation in clinical trials in the Adult and Late Life Depression Clinic at the New York State Psychiatric Institute. After a telephone screen to rule out exclusions for enrollment in the clinic, a psychiatrist conducted a detailed evaluation and completed the Cumulative Illness Rating Scale (CIRS)-Geriatric [CIRS-G]. Patients with a provisional clinical diagnosis of dysthymic disorder were interviewed by a research rater (social worker or nurse) with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I disorders- Patient edition (SCID-P). Based on the psychiatrist's evaluation and the SCID-P interview, a consensus DSM-IV diagnosis was made at a staff conference.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Treatment Trial of Duloxetine in Elderly Patients With Dysthymic Disorder
Study Start Date :
Jan 1, 2006
Actual Primary Completion Date :
Sep 1, 2010
Actual Study Completion Date :
Mar 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Duloxetine

A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Administration was as a single a.m. dose.

Drug: Duloxetine
Patients were evaluated weekly for the first 6 weeks and every two weeks for the next 6 weeks. At 0, 1, 4, 8, and 12 weeks, the study psychiatrist completed the Cornell Dysthymia Rating Scale , Clinical Global Impression (CGI) scale, and side effect ratings using the Treatment Emergent Symptom Scale. The research rater completed a SCID-P at baseline and the 24-item HAM-D at each visit, and the patient completed the Beck Depression Inventory-II at each visit. Adverse events: All adverse events and serious adverse events were documented. The maximum duration of delay before active treatment (medication or psychotherapy) was 1 week. Dropout: Patients who had a CGI score of 6 or 7 for two weeks during the second half of the study were dropped by the investigator from the trial.
Other Names:
  • Cymbalta
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Hamilton Rating Scale for Depression (HAM-D, 24-item) From 0 Weeks to 12 Weeks. [Screen (0) and 12 weeks]

      The research rater completed the 24-item Hamilton Rating Scale for Depression (HAM-D) and documented the scores on each visit. Hamilton Rating Scale for Depression scores range from 0-50 with low scores or decreasing scores representing decreased severity and better outcome, and higher scores or increasing scores representing more severe depressive symptoms and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.

    Secondary Outcome Measures

    1. Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 12 [Week 0 and 12]

      Cornell Dysthymia Rating Scale scores from range 0-64. Lower or decreasing scores represent decreased severity and a better outcome, while higher or increasing scores represent more severe depression and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.

    Other Outcome Measures

    1. Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12. [0 and 12 weeks]

      The Treatment Emergent Symptom Scale (TESS) documents the presence of common side effects. There are 26 items and the total score range is 0-26. Low scores or decrease in scores represent less side effects and high scores or increase in scores represent more side effects. The change in side effect severity scores was calculated by subtracting the Week 12 score from the Week 0 score.

    2. Maximum Duloxetine Oral Dose [Week 0, 1, 2, 4, 6, 8, 10, 12]

      Maximum duloxetine oral dose

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 95 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of dysthymic disorder (SCID and DSM-IV)

    • Age 60 - 95

    • Mini-Mental State Score ≥ 24

    • 24-item Hamilton Rating Scale for Depression score 12-25

    • Willing and capable of giving informed consent

    Exclusion Criteria:
    • Current major depressive episode (SCID and DSM-IV)

    • Alcohol or substance dependence during the last year (SCID and DSM-IV)

    • Bipolar disorder, schizophrenia and other psychotic disorders(SCID and DSM-IV)

    • Clinical stroke, dementia, Huntington's disease, epilepsy or other major neurological disease

    • Acute unstable medical conditions

    • Active suicidal ideation or plan

    • Non-response to duloxetine (minimum 90 mg/day for 6 weeks) during the past year

    • A positive urine drug screen for substances of abuse or dependence

    • Sensitivity with intolerability to duloxetine

    • Use of other medications that may interact with duloxetine, including inhibitors of cytochrome P450 1A2 (CYP1A2) and cytochrome P450 2D6 (CYP2D6), e.g., quinolone antibiotics and type 1-C anti-arrhythmics. Several antidepressant medications, including most SSRIs, are inhibitors of CYP2D6 but these medications are not permitted during this antidepressant treatment trial.

    • Patients with hypertension (BP >140/90 mm Hg on 2 consecutive measurements). For patients with treated hypertension and BP >140/90, written approval must be obtained from patient's internist allowing them to participate in this study.

    • Known liver damage or disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 New York State Psychiatric Institute New York New York United States 10032

    Sponsors and Collaborators

    • New York State Psychiatric Institute
    • Eli Lilly and Company

    Investigators

    • Principal Investigator: Davangere Devanand, M.D., Columbia University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    New York State Psychiatric Institute
    ClinicalTrials.gov Identifier:
    NCT01852383
    Other Study ID Numbers:
    • 6143R
    First Posted:
    May 13, 2013
    Last Update Posted:
    May 1, 2014
    Last Verified:
    Feb 1, 2014
    Keywords provided by New York State Psychiatric Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Dose increments at these specified time-points will not occur if the patient meets criteria for remission or develops intolerable side effects that require reducing the dose or stopping the medication. Administration will be as a single a.m. dose.
    Period Title: Overall Study
    STARTED 30
    COMPLETED 19
    NOT COMPLETED 11

    Baseline Characteristics

    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Dose increments at these specified time-points will not occur if the patient meets criteria for remission or develops intolerable side effects that require reducing the dose or stopping the medication. Administration will be as a single a.m. dose.
    Overall Participants 30
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    10
    33.3%
    >=65 years
    20
    66.7%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.7
    (7.6)
    Sex: Female, Male (Count of Participants)
    Female
    17
    56.7%
    Male
    13
    43.3%
    Region of Enrollment (participants) [Number]
    United States
    30
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Hamilton Rating Scale for Depression (HAM-D, 24-item) From 0 Weeks to 12 Weeks.
    Description The research rater completed the 24-item Hamilton Rating Scale for Depression (HAM-D) and documented the scores on each visit. Hamilton Rating Scale for Depression scores range from 0-50 with low scores or decreasing scores representing decreased severity and better outcome, and higher scores or increasing scores representing more severe depressive symptoms and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.
    Time Frame Screen (0) and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Dose increments at these specified time-points will not occur if the patient meets criteria for remission or develops intolerable side effects that require reducing the dose or stopping the medication. Administration will be as a single a.m. dose.
    Measure Participants 30
    Mean (Standard Deviation) [units on a scale]
    8
    (6.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Duloxetine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Change from Week 0 to Week 12, not adjusted for multiple comparisons. Alpha=0.05 threshold for statistical significance.
    Method ANCOVA
    Comments
    2. Other Pre-specified Outcome
    Title Change in the Treatment Emergent Symptom Scale (TESS) Total Score From Week 0 to Week 12.
    Description The Treatment Emergent Symptom Scale (TESS) documents the presence of common side effects. There are 26 items and the total score range is 0-26. Low scores or decrease in scores represent less side effects and high scores or increase in scores represent more side effects. The change in side effect severity scores was calculated by subtracting the Week 12 score from the Week 0 score.
    Time Frame 0 and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Dose increments at these specified time-points will not occur if the patient meets criteria for remission or develops intolerable side effects that require reducing the dose or stopping the medication. Administration will be as a single a.m. dose.
    Measure Participants 30
    Mean (Standard Deviation) [units on a scale]
    5.2
    (3.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Duloxetine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.1
    Comments Change from Week 0 to Week 12, not adjusted for multiple comparisons. Alpha=0.05 threshold for statistical significance.
    Method Corrlation
    Comments
    3. Secondary Outcome
    Title Change in Cornell Dysthymia Rating Scale Scores From Week 0 to Week 12
    Description Cornell Dysthymia Rating Scale scores from range 0-64. Lower or decreasing scores represent decreased severity and a better outcome, while higher or increasing scores represent more severe depression and a worse outcome. The change score was calculated by subtracting the Week 12 score from the Week 0 score.
    Time Frame Week 0 and 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Administration was as a single a.m. dose. Duloxetine: Patients were evaluated weekly for the first 6 weeks and every two weeks for the next 6 weeks. At 0, 1, 4, 8, and 12 weeks, the study psychiatrist completed the Cornell Dysthymia Rating Scale, Clinical Global Impression (CGI) scale, and side effect ratings using the Treatment Emergent Symptom Scale.
    Measure Participants 30
    Mean (Standard Deviation) [units on a scale]
    28.8
    (10.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Duloxetine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Change from Week 0 to Week 12, not adjusted for multiple comparisons. Alpha=0.05 threshold for statistical significance.
    Method ANCOVA
    Comments
    4. Other Pre-specified Outcome
    Title Maximum Duloxetine Oral Dose
    Description Maximum duloxetine oral dose
    Time Frame Week 0, 1, 2, 4, 6, 8, 10, 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Administration was as a single a.m. dose. Duloxetine: Patients were evaluated weekly for the first 6 weeks and every two weeks for the next 6 weeks. At 0, 1, 4, 8, and 12 weeks, the study psychiatrist completed the Cornell Dysthymia Rating Scale, Clinical Global Impression (CGI) scale, and side effect ratings using the Treatment Emergent Symptom Scale.
    Measure Participants 30
    Mean (Standard Deviation) [mg]
    101
    (38.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Duloxetine
    Comments Correlation of maximum duloxetine dose with change in Hamilton Depression Rating Scale scores from 0 Weeks to 12 Weeks.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <.001
    Comments Pearson correlation coefficient. Not adjusted for multiple comparisons. Alpha=0.05 for statistical significance threshold.
    Method Pearson correlation
    Comments

    Adverse Events

    Time Frame Assessments were completed once a week throughout the 12-week trial.
    Adverse Event Reporting Description
    Arm/Group Title Duloxetine
    Arm/Group Description A minimum 1-week psychotropic medication washout, and a washout of 3 weeks for fluoxetine and monoamine oxidase inhibitors(MAOIs), was required. Duloxetine was prescribed at 20 mg daily for the first week, 30 mg daily for the second week, then 60 mg daily for another 4 weeks. Patients could subsequently be raised to 90 mg daily for another 2-4 weeks and then to a maximum dose of 120 mg daily. At all visits, the study psychiatrist had the option of adjusting the dose based on clinical response and side effects. Dose increments at these specified time-points will not occur if the patient meets criteria for remission or develops intolerable side effects that require reducing the dose or stopping the medication. Administration will be as a single a.m. dose.
    All Cause Mortality
    Duloxetine
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Duloxetine
    Affected / at Risk (%) # Events
    Total 0/30 (0%)
    Other (Not Including Serious) Adverse Events
    Duloxetine
    Affected / at Risk (%) # Events
    Total 7/30 (23.3%)
    Gastrointestinal disorders
    Constipation and Anorgasmia 1/30 (3.3%) 1
    Diarrhea 1/30 (3.3%) 1
    Nausea 1/30 (3.3%) 1
    General disorders
    Fall 1/30 (3.3%) 1
    Nervous system disorders
    Tremor 1/30 (3.3%) 1
    Insomnia 1/30 (3.3%) 1
    Sedation 1/30 (3.3%) 1

    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/Title Dr. D.P. Devanand
    Organization New York State Psychiatric Institute
    Phone (646) 774-8658
    Email dpd3@columbia.edu
    Responsible Party:
    New York State Psychiatric Institute
    ClinicalTrials.gov Identifier:
    NCT01852383
    Other Study ID Numbers:
    • 6143R
    First Posted:
    May 13, 2013
    Last Update Posted:
    May 1, 2014
    Last Verified:
    Feb 1, 2014