Clinical trial NCT02139540: Nitrous Oxide as Treatment for Major Depression - a Pilot Study
Official title: Nitrous Oxide as Treatment for Major Depression - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depression
Major Depressive Disorder
Keywords: Treatment
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-05-15
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Change in Hamilton Depression Rating Scale HDRS-21
timeFrame: baseline and 24 hours
Secondary outcomes:
measure: Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR
timeFrame: baseline and 24 hours
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Peter Nagele, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: