A New Treatment Approach for Major Depressive Disorder Based Upon Targeting Monoamine Oxidase A (MAO-A)

Study Overview
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Brief Summary
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The investigators will be looking at MAO-A density before and after seven weeks of treatment with an antidepressant and dietary supplement. MAO-A is an enzyme that breaks down brain chemicals that regulate mood. MAO-A density is elevated in patients with major depressive episodes (MDE) secondary to major depressive disorder (MDD). Many remain treatment resistant with common antidepressant treatments and we think it may be due to poor targeting of brain pathologies. We want to test if adding a dietary supplement may normalize MAO-A.

Detailed Description
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All subjects are getting the combined treatment of a selective serotonin reuptake inhibitor and the dietary supplement. There are two possible selective serotonin reuptake inhibitor treatments but the dietary supplement remains the same. No subjects are receiving the selective serotonin reuptake inhibitor alone and no subjects are receiving the dietary supplement alone. The dietary supplement is called n-acetylcysteine.

Official Title
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A New Biomarker-Based Approach Towards Developing Improved Treatment for Major Depressive Disorder (MDD) Based Upon Targeting Monoamine Oxidase A (MAO-A)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Sertraline
* Drug: Citalopram
* Drug: N-acetylcysteine (NAC)
* Drug: Existing depression medication treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV diagnosis of current major depressive episode and major depressive disorder Hamilton Depression Rating Scale score of at least 20 Exclusion Criteria: Comorbid axis I or II disorders Antidepressant use in past 6 months Current use of herbal remedies Cigarette smoking Drug or medication use within past 8 weeks History of substance abuse/neurotoxin use History of psychotic symptoms History of CNS medical illness Current substance use Test positive on pregnancy test (women)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertraline and n-acetylcysteine<br>Sertraline and n-acetylcysteine for seven weeks of treatment | Drug: Sertraline<br>* selective serotonin reuptake inhibitor<br>* Other names: Zoloft;Drug: N-acetylcysteine (NAC)<br>* natural health product<br>|
| Experimental: Citalopram and n-acetylcysteine<br>Citalopram and n-acetylcysteine for seven weeks of treatment | Drug: Citalopram<br>* selective serotonin reuptake inhibitor<br>* Other names: Celexa;Drug: N-acetylcysteine (NAC)<br>* natural health product<br>|
| Experimental: Existing medication treatment & NAC<br>Existing depression medication treatment and n-acetylcysteine for seven weeks of treatment | Drug: N-acetylcysteine (NAC)<br>* natural health product<br>Drug: Existing depression medication treatment<br>* Continuation of depression medication treatment already taken prior to study enrollment except for drugs with affinity for MAO-A or potentially influencing MAO-A levels, including phenelzine, tranylcypromine, moclobemide, cytomel and lithium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAO-A distribution volume with positron emission tomography | Treatment take 1 week for titration and 6 weeks at full dose=7weeks average | before and after treatment, 7 weeks on average between measures | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale Score | Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average | before and after treatment, 7 weeks on average between measures | 
| Magnetic Resonance Spectroscopy (n-acetylaspartate and glutathione levels) | Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average | before and after treatment, 7 weeks on average between measures | 
| Blood markers of monoamine oxidase-A fragment level and glutathione level | Treatment takes 1 week for titration and 6 weeks at full dose=7 weeks average | before and after treatment, 7 weeks on average between measures |