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.