COVID-19 pandemic

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.

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