Nitrous Oxide as Treatment for Major Depression - a Pilot Study

NCT ID: NCT02139540

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2015-04-30

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.

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.

Conditions

Depression; Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

N2O/Placebo

First session: Nitrous oxide Second session: placebo

Group Type: OTHER

Nitrous Oxide

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

50% nitrogen \[inert\]/50% oxygen - otherwise completely identical administration and setup

Placebo/N2O

First session: Placebo Second session: Nitrous Oxide

Group Type: OTHER

Nitrous Oxide

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

50% nitrogen \[inert\]/50% oxygen - otherwise completely identical administration and setup

Interventions

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.

Intervention Type: DRUG

Placebo

50% nitrogen \[inert\]/50% oxygen - otherwise completely identical administration and setup

Intervention Type: DRUG

Other Intervention Names

Laughing Gas; 50% nitrogen [inert]/50% oxygen

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Nagele, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Barnes-Jewish Hospital

St Louis, Missouri, United States

Countries

United States

References

de Leon VC, Kumar A, Nagele P, Palanca BJ, Gott B, Janski A, Zorumski CF, Conway CR. Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis. J Clin Psychiatry. 2023 Aug 16;84(5):22br14725. doi: 10.4088/JCP.22br14725. No abstract available.

Reference Type: DERIVED

PMID: 37585253 (View on PubMed)

Other Identifiers

201204023

Identifier Type: -

Identifier Source: org_study_id