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

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.

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