Inclusion Criteria:
* patients with major depressive disorder (MDD) or bipolar disorder (BD)
* patients with documented treatment resistant disorder (TRD) (according to Diagnostic Statistical Manual (DSM-IV TR)), and who have failed (defined as patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose) of at least two trials of first line evidence-based treatments and/or electroconvulsive therapy (ECT)
Exclusion Criteria:
* Being younger than 18 of age or older than 65.
* Diagnosed with intellectual disability, e.g. mental retardation (MR), neurodegenerative diseases, e.g. early-onset neurocognitive disturbances such as frontotemporal dementia (FTD) or behavioral disorders, e.g. adult onset Attention Deficit Hyperactivity Disorder (ADHD).
* Diagnosed with bipolar disorder not otherwise specified (BD-NOS) or rapid cycling BD
* Diagnosed with personality disorders (PD).
* Previously or currently diagnosed with psychosis (schizoaffective disorder - SAD) or schizophrenia - SCZ).
* Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., obstructive sleep apnea requiring Continuous Positive Airway Pressure (CPAP), liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases); history of any brain diseases, including seizures, stroke, meningitis, encephalitis, dementia, degenerative brain diseases, and head injury with loss of consciousness for any period of time.
* Diagnosed specifically with a cardiovascular disorders such as Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) or suffering from Chronic Obstructive Pulmonary Disease (COPD) or asthma. Suffering from uncontrolled hypertension or diastolic BP over 100. Cardiac clearance prior to enrolling in the study/medical records from physician will be required per patient's primary care physician (PCP).
* Patients with increased risk of laryngospasm, active upper respiratory infections, respiratory depression, increased intracranial pressure, hyperthyroidism, or porphyria.
* Current substance abuse or dependence. Only patients who achieved stable, full remission for at least 6 months will be included.
* Pregnancy or Breast feeding. All female in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study.
* Unable to understand the design and requirements of the study
* Unable to sign the informed consent for any reason
* An assigned responsible adult has provided assent to assist in patient's study participation. The responsible adult agrees to be present at each study appointment as well as provide transportation to study appointments for the patient.