Depressive Disorder NOS, Dysthymic Disorder
Conditions
Keywords
dysthymia, dysthymic disorder, chronic depression, chronic low-grade depression, atypical depression, minor depression, depression NOS, depression, depressive disorder, mood disorder, unipolar depression, low-grade depression
Brief summary
The investigators are studying a new antidepressant medicine, duloxetine, for the treatment of people with chronic depression. Duloxetine (trade name Cymbalta) was recently approved by the FDA for the treatment of major depression. The investigators are testing whether this medicine is also effective for adults with chronic depression (dysthymic disorder or dysthymia). Chronic depression, lasting two or more years, often causes significant suffering and impairment. The investigators study involves a 6 to 10 week double-blind Initial Phase during which half of the participants will take the new medication and half will take a placebo (an inactive look-alike pill). After the Initial Phase, a 12-week Continuation Phase will begin, during which all subjects can be treated with an FDA-approved antidepressant medication. Eligible subjects may also receive MRI scans, to help the investigators understand how antidepressants work in treating depression.
Detailed description
This is a 22-week study of the tolerability, dosing, and efficacy of duloxetine in chronically depressed outpatients. Participants can have Dysthymic Disorder (Dysthymia), or Depression, Not Otherwise Specified (Depression NOS). The first 10 weeks (Acute Phase) are double blind, placebo-controlled, and the second 12 weeks (Continuation Phase) is open-label and all subjects will receive active medication. Tests of cytokine functioning will be performed and analyzed for treatment and placebo effects. In addition, a subset of patients will be enrolled into an Magnetic Resonance Imaging (MRI) sub-study, in which a variety of brain imaging techniques (including anatomical MRI, functional MRI (fMRI), MR Spectroscopy, and Diffusion Tensor Imaging) will be performed at baseline and week 10. Duloxetine responders will have a third MRI performed at week 22.
Interventions
DRUGDuloxetine (Cymbalta)
duloxetine medication up to dose of 120 mg/day
Sponsors
Eli Lilly and Company
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* age 20 to 75 years (ages 20 to 60 for MRI sub-study) * diagnosis of dysthymic disorder (chronic depression) or depression NOS * minimum of 2 years duration of current episode of depression
Exclusion criteria
* current major depression * diagnoses including delirium, dementia, bipolar disorder, schizophrenia * substance abuse or dependence in the past 6 months * pregnant or nursing women * serious risk of suicide
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS) - 24 Total Score | Week 10 | HDRS-24 total score, standardly used rating scale for depression. Score 0-7 no depression; Score 8-16 mild depression; Score 17-23 moderate depression; Score 24 and up severe depression. Range= 0 to 75, higher score=worse depression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cornell Dysthymia Rating Scale (CDRS) | Week 10 | CDRS is a 20-item clinician-rated inventory for chronic depressive symptoms. Each item was characterized by an explanatory or illustrative description and rated from 0 (symptom absent) to 4 (severe symptoms). Scores from 0 to 82 with higher score indicating worse depression |
| Global Assessment of Functioning Scale (GAF) | Week 10 | A commonly used rating scale for global social function. Range from 0 to 100; higher score=better functioning. 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 no more than slight impairment in social, occupational, or school functioning (e.g., temporarily falling behind in schoolwork). 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Some impairment in reality testing or communication 21 - 30 Behavior is considerably influenced by delusions or hallucinations or serious impairment, in communication or judgment 11 - 20 Some danger of hurting self or others 1 - 10 Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. 0 Inadequate information |
| Beck Depression Inventory (BDI) | Week 10 | Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-offs are as follows:\[7\] 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms. |
| Clinical Global Impressions Improvement(CGI-I) | 10 weeks | The Clinical Global Impression - Improvement(CGI-I) is a 7-point scale that rate patient's total improvement whether or not comparing to his/her condition at baseline. 0 = Not assessed 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse Higher score=greatest worsening |
Other
| Measure | Time frame | Description |
|---|---|---|
| Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI) | Baseline | To use resting-state fMRI to study the effects of antidepressant therapy on default mode network (DMN) connectivity density. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by advertisements, website postings, and from the hospital's telephone referral service. Conducted between August 2006 and December 2011. Potential participants provided informed consent for study participation. A physical examination was performed and blood and urine samples were collected, including urine toxicology.
Pre-assignment details
For patients on current ineffective psychotropic medication, washout was required, with \>=7 days medication-free (\>=28 days for fluoxetine). Concurrent sleep medication (zolpidem) was allowed for a maximum of 5 days during the study.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine (Cymbalta) Duloxetine medication, ranging from 30 to 120 mg/day | 33 |
| Placebo Treatment placebo treatment: treatment with placebo capsules that match active medication capsules | 32 |
| Total | 65 |
Baseline characteristics
| Characteristic | Placebo Treatment | Duloxetine (Cymbalta) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 32 Participants | 64 Participants |
| Age, Continuous | 42.1 years STANDARD_DEVIATION 11.4 | 41 years STANDARD_DEVIATION 11.7 | 41.6 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment United States | 32 participants | 33 participants | 65 participants |
| Sex: Female, Male Female | 10 Participants | 18 Participants | 28 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 29 | 22 / 28 |
| serious Total, serious adverse events | 0 / 33 | 0 / 32 |
Outcome results
Primary
Hamilton Depression Rating Scale (HDRS) - 24 Total Score
HDRS-24 total score, standardly used rating scale for depression. Score 0-7 no depression; Score 8-16 mild depression; Score 17-23 moderate depression; Score 24 and up severe depression. Range= 0 to 75, higher score=worse depression
Time frame: Baseline
Population: Patients for whom post-baseline data was available and scored 2 or less on the suicide item either at baseline or during the course of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Hamilton Depression Rating Scale (HDRS) - 24 Total Score | 14.1 Scores on a scale | Standard Deviation 3.8 |
| Placebo Treatment | Hamilton Depression Rating Scale (HDRS) - 24 Total Score | 14.9 Scores on a scale | Standard Deviation 3.5 |
Primary
Hamilton Depression Rating Scale (HDRS) - 24 Total Score
HDRS-24 total score, standardly used rating scale for depression. Score 0-7 no depression; Score 8-16 mild depression; Score 17-23 moderate depression; Score 24 and up severe depression. Range= 0 to 75, higher score=worse depression
Time frame: Week 10
Population: Patients for whom post-baseline data was available and scored 2 or less on the suicide item either at baseline or during the course of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Hamilton Depression Rating Scale (HDRS) - 24 Total Score | 5 Scores on a scale | Standard Deviation 3.6 |
| Placebo Treatment | Hamilton Depression Rating Scale (HDRS) - 24 Total Score | 10 Scores on a scale | Standard Deviation 5.5 |
Comparison: Repeated measures ANOVA was used to compare measures between baseline and week 10.p-value: 0.003Repeated Measures ANOVA
Secondary
Beck Depression Inventory (BDI)
Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-offs are as follows:\[7\] 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms.
Time frame: Week 10
Population: subjects fro whom post-baseline data was available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Beck Depression Inventory (BDI) | 8.5 Scores on a scale | Standard Deviation 7 |
| Placebo Treatment | Beck Depression Inventory (BDI) | 10.1 Scores on a scale | Standard Deviation 6.2 |
Comparison: Repeated measures ANOVA was used to compare measures between baseline and week 10.p-value: 0.6Repeated measures ANOVA
Secondary
Beck Depression Inventory (BDI)
Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-offs are as follows:\[7\] 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms.
Time frame: Baseline
Population: subjects for whom post-baseline data was available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Beck Depression Inventory (BDI) | 12.7 Scores on a scale | Standard Deviation 5.8 |
| Placebo Treatment | Beck Depression Inventory (BDI) | 15.5 Scores on a scale | Standard Deviation 5.5 |
Secondary
Clinical Global Impressions Improvement(CGI-I)
The Clinical Global Impression - Improvement(CGI-I) is a 7-point scale that rate patient's total improvement whether or not comparing to his/her condition at baseline. 0 = Not assessed 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse Higher score=greatest worsening
Time frame: 10 weeks
Population: subjects for whom post-baseline data was available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Clinical Global Impressions Improvement(CGI-I) | 2.4 Scores on a scale | Standard Deviation 0.8 |
| Placebo Treatment | Clinical Global Impressions Improvement(CGI-I) | 3 Scores on a scale | Standard Deviation 1.1 |
Secondary
Cornell Dysthymia Rating Scale (CDRS)
CDRS is a 20-item clinician-rated inventory for chronic depressive symptoms. Each item was characterized by an explanatory or illustrative description and rated from 0 (symptom absent) to 4 (severe symptoms). Scores from 0 to 82 with higher score indicating worse depression
Time frame: Week 10
Population: subjects for whom data post baseline were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Cornell Dysthymia Rating Scale (CDRS) | 19.1 scores on a scale | Standard Deviation 9.5 |
| Placebo Treatment | Cornell Dysthymia Rating Scale (CDRS) | 28.5 scores on a scale | Standard Deviation 14.6 |
Comparison: Repeated measures ANOVA was used to compare measures between baseline and week 10.p-value: 0.05Repeated Measures ANOVA
Secondary
Cornell Dysthymia Rating Scale (CDRS)
CDRS is a 20-item clinician-rated inventory for chronic depressive symptoms. Each item was characterized by an explanatory or illustrative description and rated from 0 (symptom absent) to 4 (severe symptoms). Scores from 0 to 82 with higher score indicating worse depression
Time frame: Baseline
Population: subjects for whom data post baseline were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Cornell Dysthymia Rating Scale (CDRS) | 36.9 Scores on a scale | Standard Deviation 8 |
| Placebo Treatment | Cornell Dysthymia Rating Scale (CDRS) | 37.4 Scores on a scale | Standard Deviation 8 |
Secondary
Global Assessment of Functioning Scale (GAF)
A commonly used rating scale for global social function. Range from 0 to 100; higher score=better functioning. 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 no more than slight impairment in social, occupational, or school functioning (e.g., temporarily falling behind in schoolwork). 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Some impairment in reality testing or communication 21 - 30 Behavior is considerably influenced by delusions or hallucinations or serious impairment, in communication or judgment 11 - 20 Some danger of hurting self or others 1 - 10 Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. 0 Inadequate information
Time frame: Week 10
Population: subjects for whom post-baseline data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Global Assessment of Functioning Scale (GAF) | 69.9 points on rating scale | Standard Deviation 20.9 |
| Placebo Treatment | Global Assessment of Functioning Scale (GAF) | 65.7 points on rating scale | Standard Deviation 14 |
Comparison: Repeated measures ANOVA was used to compare measures between baseline and week 10.p-value: 0.025Repeated measures ANOVA
Secondary
Global Assessment of Functioning Scale (GAF)
A commonly used rating scale for global social function. Range from 0 to 100; higher score=better functioning. 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 no more than slight impairment in social, occupational, or school functioning (e.g., temporarily falling behind in schoolwork). 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Some impairment in reality testing or communication 21 - 30 Behavior is considerably influenced by delusions or hallucinations or serious impairment, in communication or judgment 11 - 20 Some danger of hurting self or others 1 - 10 Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. 0 Inadequate information
Time frame: Baseline
Population: subjects for whom post-baseline data were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Global Assessment of Functioning Scale (GAF) | 62.6 points on rating scale | Standard Deviation 5.8 |
| Placebo Treatment | Global Assessment of Functioning Scale (GAF) | 58.3 points on rating scale | Standard Deviation 7 |
Other Pre-specified
Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI)
To use resting-state fMRI to study the effects of antidepressant therapy on default mode network (DMN) connectivity density.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI) | 0.21 percentage of connecting nods | Standard Deviation 0.08 |
| Placebo Treatment | Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI) | 0.24 percentage of connecting nods | Standard Deviation 0.06 |
p-value: 0.002t-test, 2 sided
Other Pre-specified
Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI)
To use resting-state fMRI to study the effects of antidepressant therapy on default mode network (DMN) connectivity density.
Time frame: Follow up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine (Cymbalta) | Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI) | 0.16 percentage of connecting nods | Standard Deviation 0.06 |
| Placebo Treatment | Resting-state Functional Connectivity Magnetic Resonance Imaging(fMRI) | 0.19 percentage of connecting nods | Standard Deviation 0.08 |
p-value: 0.9t-test, 2 sided