Clinical Trial: Duloxetine for Chronic Depression: a Double-blind Study
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Duloxetine for Chronic Depression: a Double-blind Study
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 Summary:
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.
Sponsor: New York State Psychiatric Institute
Current Primary Outcome:
- Hamilton Depression Rating Scale (HDRS) - 24 Total Score [ Time Frame: 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
- Hamilton Depression Rating Scale (HDRS) - 24 Total Score [ Time Frame: Baseline ]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
Original Primary Outcome:
- Hamilton Depression Rating Scale
- Clinical Global Impressions
Current Secondary Outcome:
- Cornell Dysthymia Rating Scale (CDRS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
- Magnetic Resonance Imaging, Anatomical [ Time Frame: 10 weeks, 22 weeks ]
- Chronic depression vs. normal differences: we expect to find abnormal brain region volumes in several regions compared to norms. Specifically: Frontal Cortex: decreased dorsal prefrontal volume, and reduced grey matter in subgenual prefrontal cortex; reduced orbitofrontal cortex gray matter volume; decreased hippocampal volume; decreased amygdala volume; decreased caudate volume; decreased putamen volume
- treatment vs. placebo differences: following active treatment, we hypothesize that volumes will change in the direction of normal in the hippocampus, prefrontal cortex, subgenual cortex, and amygdala
- responder vs. non-responder differences: greater changes in the areas found in hypothesis 2 are expected in treatment responders compared to non-responders
- Clinical Global Impressions Improvement(CGI-I) [ Time Frame: 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
- = Very much improved
- = Much improved
- = Minimally improved
- = No change
- = Minimally worse
- = Much worse
- = Very much worse Higher score=greatest worsening
- Magnetic Resonance Imaging, Functional (fMRI) [ Time Frame: 10 weeks ]
Functional brain imaging tests, including measures of cognitive conflict (Simon Task) and affective activation (Affective circumplex task) fMRI
a. Simon Task: i. We expect reduced frontal cortex activation in depressed subjects, and ii. normalization of frontal cortex activation following treatment. b. Affective Circumplex Task: i. Reduced amygdala and hippocampal activation in depressed subjects, ii. normalization of activation in these areas following treatment.
- Magnetic Resonance Spectroscopic Imaging (MRSI) [ Time Frame: 10 weeks ]Magnetic resonance spectroscopic imaging. We expect to find decreased levels of N-Acetyl-Aspartate (NAA) in frontal cortex (dorsal prefrontal, subgenual prefrontal cortex, and orbitofrontal cortex gray matter), as well as in hippocampus, amygdala, caudate, and putamen.
- Co
Original Secondary Outcome:
- Cornell Dysthymia Rating Scale
- Global Assessment of Functioning Scale
- Beck Depression Inventory
- Magnetic Resonance Imaging, Anatomical
- Magnetic Resonance Imaging, Functional
- Magnetic Resonance Spectroscopy
Information By: New York State Psychiatric Institute
Dates:
Date Received: August 3, 2006
Date Started: August 2006
Date Completion:
Last Updated: April 25, 2016
Last Verified: October 2013
