Desvenlafaxine vs. Placebo Treatment of Chronic Depression

Study Overview
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Brief Summary
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The investigators are studying a new antidepressant medicine, desvenlafaxine, for the treatment of people with chronic depression. Desvenlafaxine (trade name Pristiq) has been approved by the FDA for the treatment of major depression. The investigators are testing whether this medicine is also effective for adults with a type of chronic depression that is less severe than major depression. This condition is also known as dysthymic disorder or dysthymia. Chronic depression, lasting two or more years, often causes significant suffering and impairment. In addition, the investigators are using MRI imaging, which uses magnetic signals to make pictures of the brain's structure and also of its functioning. The purpose of MRI imaging in this study is to see whether chronic depression is associated with differences in brain structure or functioning, and whether such differences change after medication or placebo treatment. To test this MRI scans are done at the start of the study and after 12 weeks of medication or placebo treatment. Getting MRI imaging will be an option for participants in this study but is not required. This study involves a 6 to 12 week double-blind period during which half of the participants will take the new medication and half will take a placebo (an inactive look-alike pill). After the double blind phase, all subjects can be treated for 12 weeks with an FDA-approved antidepressant medication. Assessments (of depressive symptoms, social functioning, and personality) will be done by study staff and by patients before the study starts, at each study visit for the first 12 weeks, and again after 24 weeks in the study.

Detailed Description
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The investigators wish to study acute efficacy for 12 weeks on a double blind basis and continued response after open-label treatment at week 24 follow-up. It is important to establish the acute (12 week) efficacy of desvenlafaxine in non-major chronic depression. Also, given that non-major chronic depression is by definition chronic, it is important to demonstrate that benefit persists at follow-up assessment (24 weeks); this is clinically important in trying to alleviate the significant psychosocial morbidity associated with this disorder. The investigators believe this study will have significant value in the treatment of patients with non-major chronic depression, and will add significantly to what remains an extremely small scientific literature. The investigators would also like to study the effects of desvenlafaxine on brain structure and function. Learning that a medication reduces symptoms does not teach us how the medication achieves this outcome. Participants in this study can have the opportunity to participate in MRI scanning that will help to understand the mechanisms by with desvenlafaxine is effective. MRI scans are done prior to starting the clinical trial and then again after completing the double blind clinical trial.

Official Title
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Desvenlafaxine (Pristiq) vs. Placebo in the Treatment of Chronic Depression

Conditions
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Dysthymic Disorder, Dysthymia, Chronic Depressive Disorder

Intervention / Treatment
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* Drug: Desvenlafaxine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female outpatients 20 to 65 years of age, inclusive Principal DSM-5 diagnosis of unipolar non-major Chronic Depressive Disorder (including Major Depression in partial remission, Major Depression, residual, Dysthymic Disorder, or Depressive Disorder NOS) Minimum of 2 years duration of the current episode of depressive disorder. Score of 12 or higher on the Hamilton Depression Scale (24 items) at baseline Exclusion Criteria: Full remission of depression in past 24 months Current major depression diagnosis, psychotic illness Current risk of suicide Drug or alcohol abuse/dependence in past 6 months Active medical illness Prior nonresponse to desvenlafaxine Medical illness contraindicating use of desvenlafaxine Current or planned pregnancy during study period

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Desvenlafaxine<br>Serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressant drug | Drug: Desvenlafaxine<br>* Desvenlafaxine oral dose ranging from 50 to 100 mg/day<br>* Other names: Pristiq;|
| Placebo Comparator: Placebo<br>Placebo treatment | Drug: Placebo<br>* Matching placebo pills<br>* Other names: Inactive comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression (HDRS24) | 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 | 
| Hamilton Rating Scale for Depression (HDRS24) | 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 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Assessment of overall improvement: based on HDRS and Clinical Global Improvement Scale Response Rate is defined as 50% improvement of Hamd24 summary scores from baseline. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dysthymia, Non-major chronic depression, Chronic depressive disorder, Antidepressant treatment, Dysthymic disorder, Chronic non-major depression