5-HTP and Creatine for Depression R33 Phase

Inclusion Criteria:

* Adults age 18-65 years inclusive
* Current diagnosis of MDD identified by the MINI (Mini Neuropsychiatric Interview)
* Current HAM-D17 score of \>= 16
* Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks
* Right-handed
* Residing at \> 4000 ft for at least 12 weeks

Exclusion Criteria:

* Any non-MDD and non-anxiety psychiatric diagnosis, as identified by the MINI
* History of or current diagnosis of renal disease, such as chronic renal failure, acute renal failure or end stage renal disease
* Current colitis or diverticulitis
* History of or current pulmonary disease (except well controlled asthma)
* Current smoking
* History of cardiac disease or QTc \> 500ms
* History of fibromyalgia or any 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/SNRI antidepressant except for bupropion at FDA-approved doses or trazodone up to 200mg, or use of any supplements apart from standard multivitamins
* Positive pregnancy test, pregnancy, failure to use adequate birth control method
* Previous diagnosis of serotonin syndrome or evidence of serotonin syndrome
* Pre-existing eosinophilia (absolute eosinophil count \> 500/uL)
* Contraindications to MRI: ferromagnetic implants, implanted devices, claustrophobia