Duloxetine for Chronic Depression: a Double-blind Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Duloxetine for Chronic Depression: a Double-blind Study

Conditions
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Dysthymic Disorder, Depressive Disorder NOS

Intervention / Treatment
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* Drug: Duloxetine (Cymbalta)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: duloxetine (cymbalta)<br>Duloxetine medication: a medication currently marketed in the USA that is reported to have pharmacological effects including reuptake blockage for serotonin and norepinephrine | Drug: Duloxetine (Cymbalta)<br>* duloxetine medication up to dose of 120 mg/day<br>* Other names: Cymbalta;|
| Placebo Comparator: Placebo treatment<br>placebo treatment: treatment with placebo capsules that match active medication capsules | Drug: Duloxetine (Cymbalta)<br>* duloxetine medication up to dose of 120 mg/day<br>* Other names: Cymbalta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Week 10 | 
| 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 | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Week 10 | 
| 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 | Week 10 | 
| 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. | Week 10 | 
| 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 = Very much improved = Much improved = Minimally improved = No change = Minimally worse = Much worse = Very much worse Higher score=greatest worsening | 10 weeks | 
| 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 | Baseline | 
| 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. | Baseline | 
| 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 | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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