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

Brent Michael Kious, MD, PhD

Status and phase

Terminated

Phase 4

Conditions

Major Depressive Disorder

Treatments

Drug: 5-hydroxytryptophan and Creatine

Other: Placebo control

Study type

Interventional

Funder types

Other

Identifiers

NCT02922725

94176

Details and patient eligibility

About

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.

Full description

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.

Enrollment

32 patients

Sex

Female

Ages

25 to 40 years old

Volunteers

Accepts Healthy Volunteers

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