Biomarkers / Blood, Biomarkers / Hair, EEG, Nitrous Oxide, Suicidal Ideation, Suicidality
Conditions
Keywords
suicidality, nitrous oxide, suicidal ideation, depression
Brief summary
The primary aim of the NITOS study is to investigate the potential rapid antisuicidal effects of N2O in the transdiagnostic treatment of suicidal ideation. On day 1, patients will receive either nitrous oxide (50% N2O balanced with oxygen) or placebo (50% oxygen balanced with air). Seven days after the first inhalation, a second inhalation will be performed. All patients will receive N2O at least once during this trial. While the first inhalation will be double-blind, only the patients but not the raters will be blinded to the second inhalation (day 8). For mechanism of action and prediction, a nested biomarker substudy will employ multimodal techniques including analysis of hair and blood samples, and EEG.
Interventions
DRUG50% N2O plus 50% O2
Inhalation of 50% N2O plus 50% O2 for 45 min
DRUGOxygen (O2)
50% O2 plus 50% air for 45 min
Sponsors
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ability to give written informed consent * Moderate to severe suicidal ideation defined as a score ≥3 on the Montgomery-Asberg Depression Rating Scale (MADRS; Schmidtke et al., 1985) suicide item (item #10) as well as a self-report Beck Scale for Suicide Ideation (BSS; Kliem et al., 2017) items #4 plus #5 score ≥ 2 * Plasma homocysteine level ≤ 14 µmol/l
Exclusion criteria
* Organic, including symptomatic, mental disorders (F00-F09; lifetime diagnosis) * Schizophrenia, schizotypal and delusional disorders (F20-F29; lifetime diagnosis) * Mental and behavioral disorders due to psychoactive substance use. Nicotine and cannabis will be ignored (F10-F19) * Non-medical (i.e., recreational) use of inhalational N2O during the last 12 months * Past intolerance or hypersensitivity to N2O * Critical illness * Severe cardiac disease * Pregnancy or breastfeeding * Pulmonary hypertension * Chronic cobalamin or folate deficiency unless treated with folic acid and/or vitamin B12 * History or evidence of any other medical or neurological condition that would expose the subject to an undue risk of a significant adverse event as determined by the clinical judgment of the investigator * Treatment with ketamine/esketamine during the last 4 weeks * Treatment with opioid medications during the last 3 months * Treatment with vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT) within the last 3 months * Recent (within the last 4 weeks) or current use of benzodiazepines in excess of 5 mg lorazepam or equivalent per day * Finally, any other factors that, in the investigator's judgment, would unduly impact patient safety or compliance during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beck Scale for Suicidal Ideation (BSS) | Day 0 to Day 2 | Change of BSS score between Day 0 and Day 2. Double-blind treatment with either N2O or placebo inhalation on Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Suicide Visual Analog Scale (S-VAS) | Day 1 | Briefly, the S-VAS uses the phrase urge to kill myself. Next to the phrase, the patient sees a line that is anchored on the left with the word none and on the right with the word extreme . Score ranges from 0 to 100. |
| Perceived Burdensomeness Visual Analog Scale (PB-VAS) | Day 1 | The PB-VAS uses the phrase like a burden. Next to the phrase, the patient sees a line that is anchored on the left with the word none and on the right with the word extreme . Score ranges from 0 to 100. |
| Montgomery-Åsberg Depression Rating Scale (MADRS ) | Day 0 to Day 2 | — |
| EEG changes associated with N2O / placebo inhalation | Day 1 | EEG will be performed before, during, and after inhalation |
Countries
Switzerland
Contacts
Primary ContactAngelina Frasch
Outcome results
None listed