Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females

Study Overview
=================
Brief Summary
-----------------
The investigators propose to determine if 8 weeks of dietary augmentation with oral 5g creatine monohydrate daily and 100 mg of 5-hydroxytryptophan (5-HTP) twice daily reduces hypoxia-related depressive symptoms measured by the 17-item Hamilton Depression Rating Scale (HAM-D) in women with SSRI- or SNRI-resistant depression, combined with the examination of changes in functional connectivity based on resting-state fMRI and changes in brain metabolism inferred from phosphorus-31 magnetic resonance spectroscopy.

Detailed Description
-----------------
Serotonin and creatine are processed separately in the brain, and deficits in these brain biochemicals lead to distinct clinical problems. Therefore, investigators believe that treatment with a combination therapy, which could correct both deficits, would have a synergistic effect in the treatment of hypoxia-related depression and possibly other forms of treatment-resistant depression. Thus, investigators propose to investigate antidepressant efficacy of dietary 5-hydroxytryptophan (5-HTP) and creatine, as a means to restore the brain neurotransmitter and metabolic imbalances linked to chronic hypoxia caused by high altitude residence.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression Associated With Hypobaric Hypoxia in Females

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: 5-hydroxytryptophan and Creatine
* Other: Placebo control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female gender, ages 25-40 years inclusive Current diagnosis of Major Depressive Disorder identified by the SCID-I Current HAM-D17 score of > 16 Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks Right-handed Healthy Controls Inclusion criteria: Female gender, ages 25-40 inclusive No current or past DSM-5 diagnosis, as determined by clinical and structured interviews Exclusion Criteria: Any non-MDD and non-anxiety psychiatric diagnosis, as identified by the SCID-I History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease Diabetes type I or II Current colitis or diverticulitis History of or current pulmonary disease History of cardiac disease or QTc > 500ms History of fibromyalgia, lupus, eosinophilia-myalgia syndrome, dermatomyositis, polymyositis, rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, ankylosing spondylitis, or other related rheumatological condition History of or current seizure disorder Current serious suicide risk identified by the Columbia Severity Suicide Rating Scale Current treatment with an antipsychotic, mood stabilizer, or non-SSRI antidepressant Positive pregnancy test, pregnancy, failure to use adequate birth control method Previous diagnosis of serotonin syndrome or evidence of serotonin syndrome Use of any excluded drugs or medications including serotonergic drugs or medications (Table 2) Pre-existing eosinophilia (absolute eosinophil count > 500/uL) Contraindications to MRI: ferromagnetic implants, implanted devices, claustrophobia

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Depressed patients receiving study drug<br>Participants diagnosed with MDD | Drug: 5-hydroxytryptophan and Creatine<br> <br> |
| Placebo Comparator: Depressed patients receiving placebo<br>Participants diagnosed with MDD | Other: Placebo control<br> <br> |
| No Intervention: Healthy Control<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hamilton Depression Rating Scale | The total Hamilton Depression (HAM-D) Rating Scale provides and indication of depression In general, the higher the total score the more severe the depression. HAM-D score level of depression: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe. Range: 0 to 54 | 8 weeks |