Nitrous Oxide as Treatment for Major Depression - a Pilot Study

• ClinicalTrials.gov Identifier: NCT02139540
• Recruitment Status: Completed
• First Posted: May 15, 2014
• Results First Posted: January 27, 2020
• Last Update Posted: January 27, 2020
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Depression; Major Depressive Disorder	Drug: Nitrous Oxide; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Nitrous Oxide as Treatment for Major Depression - a Pilot Study
• Actual Study Start Date: November 2012
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

Arm	Intervention/treatment
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 Name: Laughing Gas; Drug: Placebo; 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup; Other Name: 50% nitrogen [inert]/50% oxygen
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 Name: Laughing Gas; Drug: Placebo; 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup; Other Name: 50% nitrogen [inert]/50% oxygen

Outcome Measures

Primary Outcome Measures :

1. Change in Hamilton Depression Rating Scale HDRS-21 [ Time Frame: baseline and 24 hours ]
   (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.

Secondary Outcome Measures :

1. Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR [ Time Frame: baseline and 24 hours ]
   [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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Missouri

Barnes-Jewish Hospital

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

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

More Information

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02139540
• Other Study ID Numbers: 201204023
• First Posted: May 15, 2014
• Results First Posted: January 27, 2020
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

Keywords provided by Washington University School of Medicine:

Treatment

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Major; Behavioral Symptoms; Mood Disorders; Mental Disorders; Nitrous Oxide; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents