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 structuredinterviews

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, acuterenal 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 tissuedisease, 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