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

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