Duloxetine for Chronic Depression: a Double-blind Study

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.

Study Overview

• Status: Completed
• Conditions: Dysthymic Disorder; Depressive Disorder NOS
• Intervention / Treatment: Drug: Duloxetine (Cymbalta)

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: duloxetine (cymbalta); 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); duloxetine medication up to dose of 120 mg/day; Other Names: Cymbalta; duloxetine
Placebo Comparator: Placebo treatment; placebo treatment: treatment with placebo capsules that match active medication capsules	Drug: Duloxetine (Cymbalta); duloxetine medication up to dose of 120 mg/day; Other Names: Cymbalta; duloxetine

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	Follow up

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: David J. Hellerstein, MD, New York State Psychiatric Institute

Publications and helpful links

General Publications

• 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):984-91. doi: 10.4088/JCP.11m07230.
• Yang J, Hellerstein DJ, Chen Y, McGrath PJ, Stewart JW, Peterson BS, Wang Z. Serotonin-norepinephrine reuptake inhibitor antidepressant effects on regional connectivity of the thalamus in persistent depressive disorder: evidence from two randomized, double-blind, placebo-controlled clinical trials. Brain Commun. 2022 Apr 15;4(3):fcac100. doi: 10.1093/braincomms/fcac100. eCollection 2022.
• Bansal R, Hellerstein DJ, Sawardekar S, O'Neill J, Peterson BS. Effects of the antidepressant medication duloxetine on brain metabolites in persistent depressive disorder: A randomized, controlled trial. PLoS One. 2019 Jul 19;14(7):e0219679. doi: 10.1371/journal.pone.0219679. eCollection 2019.
• Hellerstein DJ, Hunnicutt-Ferguson K, Stewart JW, McGrath PJ, Keller S, Peterson BS, Chen Y. Do social functioning and symptoms improve with continuation antidepressant treatment of persistent depressive disorder? An observational study. J Affect Disord. 2017 Mar 1;210:258-264. doi: 10.1016/j.jad.2016.12.026. Epub 2016 Dec 20.

Helpful Links

• Mood Disorders Research Program website

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 3, 2006
• First Submitted That Met QC Criteria: August 3, 2006
• First Posted (Estimate): August 7, 2006

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: July 20, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: depression; mood disorder; depressive disorder; dysthymia; dysthymic disorder; chronic depression; chronic low-grade depression; atypical depression; minor depression; depression NOS; unipolar depression; low-grade depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Dysthymic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: # 4967/6363R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No