The investigators hypothesize that the administration of two widely available, naturally occurring dietary supplements, 5 hydroxytryptophan and creatine monohydrate, will reduce the severity of depression in individuals exposed to chronic hypoxia by living at altitude. The purpose of this study is to determine if 8 weeks of dietary augmentation with oral 5 g creatine daily and 100 mg 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.

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 18-64 years inclusive
• Current diagnosis of Major Depressive Disorder identified by the SCID-5-CT
• Current HAM-D17 score of > 15
• Adequate adherence to any FDA approved SSRI or SNRI for at least 8 weeks

Exclusion Criteria:

• Diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder, identified by the SCID-5-CT
• 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
• Colitis or diverticulitis
• History of pulmonary disease
• History of fibromyalgia, lupus, eosinophilia myalgia syndrome, dermatomyositis, polymyositis, rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, ankylosing spondylitis, or other related rheumatological condition
• 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
• Previous diagnosis of serotonin syndrome
• Use of any excluded drugs or medications including serotonergic drugs or medications