Nitrous TRD Bipolar Depression

Study Overview
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Brief Summary
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Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week.

Detailed Description
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Investigators will study approximately 64 patients with Treatment-Resistant Bipolar Depressive Disorder, defined as a failure of at least 1 antidepressants in the current depressive episode and 2 lifetime medication failures. The study will last approximately 6 to 8 weeks, involving randomization into one of two treatment groups receiving 3 one hour long inhalation treatments over a week. Post-treatment assessments follow each inhalation treatment and are conducted 1 week and 2 weeks following the final inhalation treatment. Patients are then randomized again into the Second Stage of the study, involving the same treatment and post-treatment schedule as the First Stage detailed above.

Official Title
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Nitrous Oxide - A Novel Therapy for Treatment-Resistant Bipolar Depression

Conditions
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Treatment- Resistant Bipolar Disorder, Bipolar Disorder, Bipolar Depressive Disorder

Intervention / Treatment
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* Drug: Nitrous Oxide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18-65 years of age Treatment-resistant bipolar depressive disorder without psychosis and a MADRS baseline score of >20. All patients must have history of being on a serum-verified (at time of entry into study) mood stabilizer [lithium at 0.5-1.2mEq/L; or valproic acid, 50-125mcg/ml] for 4 weeks prior to entry into the study and remain on this mood stabilizer during the course of the trial. Further, subjects will have failed two adequate dose/duration antidepressant courses in their lifetime, including one in the current depressive episode (verified by Antidepressant Treatment History Form). Good command of the English language Exclusion Criteria: Schizophrenia Schizoaffective disorder Obsessive-compulsive disorder or panic disorder Active or recent substance abuse or dependence (in remission at least 1 year prior to the study; exception = nicotine use disorders) A diagnosis of personality disorder that may interfere with the patient's ability to improve on nitrous oxide as determined by study investigator Acute medical illness that may pose subject at risk during nitrous oxide administration (neurological disorders or medical disorders including dementia, stroke, encephalopathy, Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac disease, any disease known to affect drug metabolism and excretion, i.e. renal or liver disease) per P.I. discretion Active suicidal intention (inability to contract for safety) Active psychotic symptoms Patients with significant pulmonary disease and/or requiring supplemental oxygen Contraindication against the use of nitrous oxide: pneumothorax; bowel obstruction; middle ear occlusion; elevated intracranial pressure; chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12; pregnant patients; breastfeeding women; previous administration of NMDA-receptor antagonists (e.g., ketamine); current electro-convulsive therapy treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) | Drug: Placebo<br>* 50% nitrogen {inert}/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)<br>|
| Experimental: Nitrous Oxide<br>50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F) | Drug: Nitrous Oxide<br>* 50% nitrous oxide/ 50% oxygen, 3 one hour inhalation treatments per Stage, every other day (M,W,F)<br>* Other names: Laughing Gas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MADRS (Montgomery Asberg Depression Rating Scale) | Change in depressive symptoms on MADRS scale between baseline and day 7 follow up | up to 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale-17 Item (Ham-D17) |  | up to1week | 
| Young Mania Rating Scale (YMRS) to Assess Emergence of Mania/Hypomania | Young Mania Rating Scale (YMRS) to assess emergence of mania/hypomania (patients with YMRS scores > 12 will be removed from the trial and recommended for follow up treatment per Psychiatry P.I., i.e., nitrous oxide treatments discontinued) | up to 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitrous Oxide, Bipolar Depressive Disorder, Treatment- Resistant Bipolar Disorder