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