Nitrous Oxide as Treatment for Major Depression - a Pilot Study

Study Overview
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Brief Summary
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Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and perhaps without the need for intravenous access and anesthesia personnel. Therefore, we propose conducting a pilot randomized placebo controlled double-blind crossover study in which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for a period of one hour in addition to standard medical therapy. Depression severity will be assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the Hamilton depression rating scale.

Detailed Description
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We will study 20 patients with non-treatment resistant major depression and 20 patients with treatment-resistant major depression, defined as failure of at least 2 antidepressants in the current depressive episode and 3 lifetime medication failures.

Official Title
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Nitrous Oxide as Treatment for Major Depression - a Pilot Study

Conditions
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Depression, Major 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 Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI). (baseline ) HDRS-21 score of >18 Good command of the English language Exclusion Criteria: History of: Bipolar disorder Schizoprenia Schizoaffective disorder Obsessive-compulsive disorder, panic disorder Substance abuse or dependence (except for remote substance abuse or dependence with remission at least 1 year prior to the study and except for nicotine use disorders) Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide Acute medical illness that may pose subject at risk during nitrous oxide administration 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) within the last 3 months Current electro-convulsive therapy treatment Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: N2O/Placebo<br>First session: Nitrous oxide Second session: placebo | Drug: Nitrous Oxide<br>* Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or placebo (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.<br>* Other names: Laughing Gas;Drug: Placebo<br>* 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup<br>* Other names: 50% nitrogen [inert]/50% oxygen;|
| Other: Placebo/N2O<br>First session: Placebo Second session: Nitrous Oxide | Drug: Nitrous Oxide<br>* Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or placebo (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.<br>* Other names: Laughing Gas;Drug: Placebo<br>* 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup<br>* Other names: 50% nitrogen [inert]/50% oxygen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale HDRS-21 | (21-point Hamilton Depression Rating Scale) Scoring is based on the first 17 items on the 21 point scale. Eight items are scored on a 5-point scale, ranging form 0=not present to 4= severe. Nine are scored from 0-2. | baseline and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR | [Quick Inventory of Depressive Symptomatology - Self Report] An item-by-item severity scale of 0 to 3, with possible total scores ranging from 0 to 84. The items on the scale are added together for a total score. Higher scores mean worse outcome. | baseline and 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment