Nitrous Oxide in the Treatment of Acute Suicidal Ideation

Inclusion criteria:

• Ability to give written informed consent

• Moderate to severe suicidal ideation defined as a score ≥3 on the Montgomery-AsbergDepression Rating Scale (MADRS; Schmidtke et al., 1985) suicide item (item #10) aswell 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 andcannabis 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 vitaminB12

• History or evidence of any other medical or neurological condition that would exposethe subject to an undue risk of a significant adverse event as determined by theclinical 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 mglorazepam or equivalent per day

• Finally, any other factors that, in the investigator's judgment, would unduly impactpatient safety or compliance during the study.