Duloxetine for Chronic Depression: a Double-blind Study

Dysthymic Disorder Clinical Trial

Official title:

Duloxetine for Chronic Depression: a Double-blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00360724
• Other study ID #: # 4967/6363R
• Status: Completed
• Phase: Phase 4
• First received: August 3, 2006
• Last updated: October 5, 2015
• Start date: August 2006
• Est. completion date: December 2013

Study information

• Verified date: October 2013
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: December 2013
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder NOS
• Disease
• Dysthymic Disorder

Intervention

Drug:
• Duloxetine (Cymbalta)
duloxetine medication up to dose of 120 mg/day

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hellerstein DJ, Stewart JW, McGrath PJ, Deliyannides DA, Batchelder ST, Black SR, Withers A, O'Shea D, Chen Y. A randomized controlled trial of duloxetine versus placebo in the treatment of nonmajor chronic depression. J Clin Psychiatry. 2012 Jul;73(7):98 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Week 10	Yes
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	Baseline	Yes
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	Week 10	No
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	Week 10	No
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.	Week 10	No
Secondary	Magnetic Resonance Imaging, Anatomical	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	10 weeks, 22 weeks	No
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; = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse Higher score=greatest worsening	10 weeks	No
Secondary	Magnetic Resonance Imaging, Functional (fMRI)	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.	10 weeks	No
Secondary	Magnetic Resonance Spectroscopic Imaging (MRSI)	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.	10 weeks	No
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	Baseline	No
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.	Baseline	No
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	Baseline	No

External Links

•   Columbia University Department of Psychiatry website
•   Mood Disorders Research Program website