Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies (NARSAD)

The Washington University

Status and phase: Completed; Phase 2

Conditions: Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Treatments: Drug: Nitrous Oxide 50%; Drug: Placebo Gas; Drug: Nitrous Oxide 25%

Study type: Interventional

Funder types: Other

Identifiers

NCT03283670

201608024

Details and patient eligibility

About

The purpose of the study aims to determine whether different concentrations of nitrous oxide (N2O) have different antidepressant effects for adults with treatment-resistant major depression.

Full description

Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD.

All patients will receive 3 randomized, one hour nitrous oxide inhalations to placebo (0% N2O), low dose (25% N2O), and high dose (50% N2O). Inhalation sessions will be at least 4 weeks apart. Mood will be assessed at baseline, 2 and 24 hours, and 1, 2, and 4 weeks post-inhalation for each dose.

Enrollment: 24 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Adults 18-75 years of age;
2. Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;
3. A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);
4. Documented (i.e., chart review) lifetime failure to respond to >=3 adequate dose/duration antidepressant treatment trials, ≥1 medication failure in the current depressive episode;
5. Good command of the English language.

Exclusion Criteria

1. Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;

2. Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;

3. Ability to become pregnant and not using effective contraception;

4. 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

5. Inability to provide informed consent;

6. Any other factor that in the investigators' judgment may affect patient safety or compliance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24 participants in 3 patient groups, including a placebo group

1. 25% nitrous oxide, 25% nitrogen, 25% oxygen

Experimental group

Description:

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Treatment:

Drug: Nitrous Oxide 25%

2. 50% nitrous oxide, 50% oxygen

Experimental group

Description:

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Treatment:

Drug: Nitrous Oxide 50%

3. Placebo gas: 50% nitrogen(inert), 50% oxygen

Placebo Comparator group

Description:

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Treatment:

Drug: Placebo Gas