Nitrous Oxide for the Treatment of Major Depressive Disorder
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/13/2019 |
| Start Date: | January 22, 2019 |
| End Date: | December 10, 2020 |
| Contact: | Carolyn Deng, MBChB |
| Email: | c.deng@alfred.org.au |
| Phone: | +61399030760 |
Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder
The investigators are conducting a randomized controlled trial to evaluate the antidepressant
effects of nitrous oxide in people with Major Depressive Disorder (MDD). MDD is a global
medical condition that causes significant health and economic burden. Recent studies have
shown that a single dose of ketamine, an NMDA-antagonist, has fast and long lasting
anti-depressant effect. Nitrous oxide, another NMDA-antagonist, is widely used for anesthesia
and analgesia, safer to administer and has fewer side effects than ketamine.
A randomized controlled crossover feasibility study showed significant reduction in
depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled
nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely
administered by any trained clinician. If found to be efficacious, it could be used to
provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has
its delayed effect. Another potential application could be in acutely suicidal patients.
This investigated-initiated phase 2b trial will enable confirmation and extension of the
findings from the feasibility study, and identify the optimal dose and regimen in a broader
population of those with MDD. Participants will be randomized to receive a weekly 1-hour
inhalational sessions of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks,
and the nitrous group will be further randomly assigned to a dose of 50% nitrous oxide or 25%
nitrous oxide. Depression severity will be assessed by a blinded observer pre-treatment and
at weekly intervals during and for 4 weeks after treatment using the Hamilton Depression
Rating Scale.
effects of nitrous oxide in people with Major Depressive Disorder (MDD). MDD is a global
medical condition that causes significant health and economic burden. Recent studies have
shown that a single dose of ketamine, an NMDA-antagonist, has fast and long lasting
anti-depressant effect. Nitrous oxide, another NMDA-antagonist, is widely used for anesthesia
and analgesia, safer to administer and has fewer side effects than ketamine.
A randomized controlled crossover feasibility study showed significant reduction in
depressive symptoms at 2 and 24 hours after a single 1-hour treatment session of inhaled
nitrous oxide compared with placebo. Nitrous oxide is inexpensive and can be safely
administered by any trained clinician. If found to be efficacious, it could be used to
provide rapid anti-depressant effect whilst the benefit of traditional anti-depressants has
its delayed effect. Another potential application could be in acutely suicidal patients.
This investigated-initiated phase 2b trial will enable confirmation and extension of the
findings from the feasibility study, and identify the optimal dose and regimen in a broader
population of those with MDD. Participants will be randomized to receive a weekly 1-hour
inhalational sessions of either nitrous oxide or placebo (oxygen-air mixture) for 4 weeks,
and the nitrous group will be further randomly assigned to a dose of 50% nitrous oxide or 25%
nitrous oxide. Depression severity will be assessed by a blinded observer pre-treatment and
at weekly intervals during and for 4 weeks after treatment using the Hamilton Depression
Rating Scale.
Inclusion Criteria:
1. Adult (≥18 years, both sexes), with DSM-IV-TR criteria for MDD without psychosis, as
determined using a structured clinical interview [Mini International Neuropsychiatric
Interview]
2. MDD, as defined by a pretreatment score >18 on the HDRS-21 scale
Exclusion Criteria:
1. A history of bipolar disorder, schizophrenia, schizoaffective disorder,
obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses; active
suicidal intention, as determined by clinical interview
2. Active or recent (<12 months) substance abuse or dependence; excluding nicotine
3. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
4. Ongoing treatment with ECT
5. Presence of acute medical illness that could interfere with study participation,
including significant pulmonary disease
6. Pregnancy or breastfeeding
7. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear
occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency
unless treated with folic acid or vitamin B12).
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