The Effects of Vilazodone on Glutamate in the Anterior Cingulate Cortex in Anxious Unipolar Depressives

Study Overview
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Brief Summary
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The purpose of this study is to determine whether vilazodone is more effective than citalopram for the treatment of anxious depression. We will use neuroimaging to see whether there are changes in the brains of patients receiving the drug vilazodone that are different from those of citalopram. These changes may show that vilazodone affects the brain differently than most other kinds of standard antidepressant medications.

Detailed Description
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This study proposes to utilize recent advances in magnetic resonance spectroscopy (MRS) techniques that permit reliable measurement of Glu in humans (9) to examine whether Vilazodone and citalopram exert differential effects on Glutamatergic neurotransmission in the ACC of anxious unipolar depressed patients. Functional connectivity as measured by Blood Oxygen Level Dependent (BOLD) MRI will be assessed to determine the relationship between the change in connectivity and the change in Glu levels with treatment. We also propose to examine, in an exploratory fashion, the relative effect of the two drugs on BOLD activation in the insula cortex.

Official Title
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The Effects of Vilazodone on Glutamate in the Anterior Cingulate Cortex in Anxious Unipolar Depressives

Conditions
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Major Depressive Disorder, Anxiety, Comorbidity

Intervention / Treatment
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* Drug: Vilazodone
* Drug: Citalopram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, aged 18-50 years. Meets DSM-IV criteria for unipolar major depression. MADRS score > 20. Subject exhibits clinically significant anxiety and HAM-A score > 15. Capable of providing informed consent. Has an established residence and phone. Exclusion Criteria: A clinically significant medical condition which could impact the response of the individual to antidepressant treatment (e.g. diabetes, cancer, lupus or other autoimmune illness). Stably treated hypothyroidism (TSH < 2) will be permitted. Beta blockers, antidepressants, antipsychotics, lithium, antiepileptic medications, steroids (oral and inhaled), chronic use of nonsteroidal antinflamatory medications (infrequent sporadic use permitted), or other medications with the potential to interfere with the antidepressant effects of Vilazodone. Pregnancy. In women of childbearing potential an unwillingness to use reliable methods to prevent pregnancy. History of manic or psychotic symptoms. History of seizure or epilepsy. History of alcohol or drug dependence and active use of substances in the past month. Active alcohol or drug abuse. Ingestion of 4 or more caffeinated beverages a day, on average.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

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: Vilazodone<br>10mg/day for 1 week, 20 mg/day for 1 week, and then 40 mg/day for 6 weeks. | Drug: Vilazodone<br>* 10mg/day for 1 week, 20 mg/day for 1 week, and then 40 mg/day for 6 weeks.<br>* Other names: Viibryd;|
| Active Comparator: Citalopram<br>20 mg/day for 2 weeks and then 40 mg/day for 6 weeks. | Drug: Citalopram<br>* 20 mg/day for 2 weeks and then 40 mg/day for 6 weeks<br>* Other names: Celexa, Cipramil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glutamate Levels | Our hypothesis that Vilazodone will increase ACC glutamate levels more than Citalopram will be addressed using a repeated measures linear regression model with ACC glutamate level as the outcome and drug (Vilazodone or Citalopram) and drug x scan time (baseline or follow-up) interaction as predictors. | Week 0 and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity | Our hypothesis that Vilazodone will decrease functional connectivity more than Citalopram will be addressed using a repeated measures linear regression model with functional connectivity correlation as the outcome and drug (Vilazodone or Citalopram) and drug x scan time (baseline or follow-up) interaction as predictors. | Week 0 and Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depressive Disorder, Anxiety, Comorbidity, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Citalopram, Vilazodone, Serotonin Uptake Inhibitors, Receptor, Serotonin, 5-HT1A