Nitrous Oxide as Treatment for Major Depression - a Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder
• Intervention / Treatment: Drug: Nitrous Oxide; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults 18-65 years of age

2. Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI).

   (baseline )

3. HDRS-21 score of >18
4. Good command of the English language

Exclusion Criteria:

History of:

1. Bipolar disorder
2. Schizoprenia
3. Schizoaffective disorder
4. Obsessive-compulsive disorder, panic disorder
5. 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)
6. Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide
7. Acute medical illness that may pose subject at risk during nitrous oxide administration
8. Active suicidal intention (inability to contract for safety)
9. Active psychotic symptoms
10. Patients with significant pulmonary disease and/or requiring supplemental oxygen

11. Contraindication against the use of nitrous oxide:

    1. Pneumothorax
    2. Bowel obstruction
    3. Middle ear occlusion
    4. Elevated intracranial pressure
    5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
    6. Pregnant patients
    7. Breastfeeding women
12. Previous administration of NMDA-receptor antagonists (e.g., ketamine) within the last 3 months
13. Current electro-convulsive therapy treatment
14. Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: N2O/Placebo; First session: Nitrous oxide Second session: placebo	Drug: Nitrous Oxide; 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.; Other Names: Laughing Gas; Drug: Placebo; 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup; Other Names: 50% nitrogen [inert]/50% oxygen
Other: Placebo/N2O; First session: Placebo Second session: Nitrous Oxide	Drug: Nitrous Oxide; 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.; Other Names: Laughing Gas; Drug: Placebo; 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup; Other Names: 50% nitrogen [inert]/50% oxygen

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Peter Nagele, MD, MSc, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: 201204023