Nitrous Oxide- Suicidal Ideation

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, the investigators of this study demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD, reducing depressive symptoms, guilt, and suicidal thinking. To more closely investigate suicidal thinking, this study is designed as a double-blind, randomized, prospective, inpatient trial comparing inhaled nitrous oxide (N2O) plus treatment as usual versus inhaled placebo plus treatment as usual. All unipolar depressed, acutely suicidal inpatients will receive standard treatment for their depression/ suicidal thinking (TAU). Additionally, participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive either inhaled nitrous oxide (50% nitrous oxide/50% oxygen = active treatment) or placebo gas (50% nitrogen/50% oxygen). A target total of 50 patients with suicidal ideation and unipolar depression will be enrolled, 25 of whom will be assigned to the TAU control group and 25 of whom will be assigned to the N2O + TAU experimental group.