Placebo-controlled Trial of 5-hydroxytryptophan and Creatine for SSRI or SNRI Augmentation in Treatment Resistant Depression in Females
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
Intervention: 5-hydroxytryptophan and Creatine; Placebo control
Intervention MeSH terms: 5-Hydroxytryptophan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 32.0
Sex: Female
Minimum age: 25 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The investigators propose to determine if 8 weeks of dietary augmentation with oral 5g
      creatine monohydrate daily and 100 mg of 5-hydroxytryptophan (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, combined with the examination of
      changes in functional connectivity based on resting-state fMRI and changes in brain
      metabolism inferred from phosphorus-31 magnetic resonance spectroscopy.
    

Eligibility criteria:

        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