Xenon Inhalation Therapy for Major Depressive Disorder and Bipolar Disorder

The investigators will test the hypothesis that inhaled xenon will produce a rapid improvement in depressive symptoms in patients suffering from treatment-resistant depression. Specifically, the investigators will conduct a parallel randomized, double-blind crossover study that will compare the effects of xenon-oxygen (35:65 ratio by volume) added to treatment as usual (X-TAU group) to the effects of nitrogen-oxygen (35:65 ratio by volume) added to treatment as usual (N-TAU group). A total of 20 severely depressed patients, 10 with major depressive disorder (MDD) and 10 with Bipolar Depression (BP), will be exposed in random order to N-TAU and X-TAU in a double-blind protocol.

Inclusion Criteria: * Patient who meets DSM-V Criteria for MDD or Bipolar Depression (according to DSM-V), as the primary focus of treatment. * Able to understand the risks and benefits of participating in this clinical trial and give informed consent, per judgment of the investigator. * Age greater than or equal to 18 years but less than or equal to 65 years. * Montgomery Asberg Depression Rating Scale ≥20. * On an adequate antidepressant regimen (MDD) or on a mood stabilizing regimen (BP) that is stable for at least four weeks prior to enrollment. * Has reliable adult transportation from and to home. * Has a treating psychiatrist who is in agreement with the patient's participation in the study, and aware of the safety plan in the protocol. * No medical contraindications to receiving a xenon- or a nitrogen-oxygen mixture. * No serious or active pulmonary disease. Exclusion Criteria: * MDD or BP disorder with psychosis, schizophrenia, OCD, or a primary anxiety disorder. * Currently taking a benzodiazepine (including PRN). * Unwilling or unable to comply with study procedures. * Active substance abuse in the past 60 days, diagnosis of substance dependence in the past 12 months, currently active smokers of any substance, including prescription marijuana. * Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception. * Any unstable medical illness (cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder). * Any history of brain injury and any active state involving entrapped air/gas within a body cavity with the potential to expand causing organ distension/compression (e.g., bowel obstruction, pneumothorax, or pneumocephalus). * History of hypersensitivity to xenon; history of multiple adverse drug reactions. * Have taken any investigational psychotropic drug within the last 6 months. * Inability to agree to comply with the visit schedule or study procedures. * Not appropriate for participation in a research trial per judgment of the investigator.