Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
Feasibility trial, Nitrous Oxide
Brief summary
The purpose of the study is to investigate a short-term treatment option for major depressive disorders by administering nitrous oxide gas. At this time, the main purpose is to complete a feasibility study with 40 participants suffering from treatment-resistant depression. Participants will be randomized to (1) Study group: Nitrous oxide (inhaled) + solution of saline (injected) and the (2) Control group: Oxygen (inhaled) + Midazolam (injected) as an Active Placebo.
Interventions
Nitrous oxide will be administered at an inspiratory concentration of 50% with concurrent intravenous saline (100ml) for one hour.
DRUGOxygen + Midazolam
Oxygen will be administered at 50% with intravenous midazolam (0.02mg/kg in 100ml) for one hour
Sponsors
Unity Health Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18 to 65 years of age 2. Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD) 3. Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5 4. Experiencing moderate to severe depressive episode, as defined by the Hamilton Depression Rating Scale (HAMD)\>17 5. Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode 6. For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant 7. Capacity to provide informed consent.
Exclusion criteria
1. Acute suicidality defined as score ≥3 on HAMD item 3 2. Major Depressive Episode in people with Bipolar Disorder 3. Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year 4. Dementia 5. Current or lifetime history of schizophrenia or schizoaffective disorder 6. Current history of dissociative disorders 7. Known history of hypersensitivity or allergy to Nitrous Oxide, Midazolam or any ingredients in the study formulations 8. Contraindication to receiving nitrous oxide 9. Chronic cobalamin or folate deficiency 10. Contraindication to receiving the placebo midazolam 11. Use of centrally acting medicinal products, such as opioid agonists, morphine derivatives, benzodiazepines and/or other central nervous system depressants such as barbiturates and alcohol 12. Pregnancy or breastfeeding in female participants 13. Electroconvulsive therapy within the current depressive episode 14. Receiving ketamine treatment within the current depressive episode 15. Unwilling to maintain current antidepressant regimen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of adverse events | 2 Years | Safety and tolerability |
| Recruitment rate | 2 Years | Recruitment rate |
| Withdrawal rate | 2 Years | — |
| Adherence rate | 2 Years | Feasibility |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Åsberg Depression Rating Scale (MADRAS) Score 0-60 (Higher scores represent higher depression). Measure changes in symptoms of depression | 6 weeks | Frequencies on numbers of 1.- Remissions (defined as MADRS score \< 10), 2.- Responses (defined as ≥ 50% reduction in MADRS score from baseline) 3.- No Responses |
| Toronto Side Effects Scale (TSES) - 32 items (each item has a score 1-25; higher score means higher intensity). Measure adverse side effects from antidepressant treatment | 6 weeks | Frequencies of safety and tolerability |
Countries
Canada
Outcome results
None listed