Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology.
Mikaela K Dimick, Danielle Omrin, Bradley J MacIntosh, Rachel H B Mitchell, Daniel Riegert, Anthony Levitt, Ayal Schaffer, Susan Belo, John Iazzetta, Garfield Detzler, Mabel Choi, Stephen Choi, Beverley A Orser, Benjamin I Goldstein
Contemporary clinical trials communications September 1, 2020 DOI: 10.1016/j.conctc.2020.100600 via PubMed
Summary
AI-generated from the abstractA randomized, double-blind trial will test whether a single administration of nitrous oxide (N2O) improves mood and increases frontal cerebral blood flow in adults with treatment-resistant bipolar depression. Participants with bipolar I or II disorder currently in a major depressive episode will be assigned to either inhaled N2O plus intravenous saline or inhaled room air plus intravenous midazolam. Mood will be assessed with the Montgomery-Asberg Depression Rating Scale, and cerebral blood flow measured by arterial spin labelling MRI. The authors suggest N2O may act as a cerebral vasodilator to counteract hypoperfusion in depression, and if effective, could become a low-cost, safe, and accessible acute treatment.
Study at a glance
| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Adults with treatment-resistant bipolar depression (BD-I or BD-II) currently experiencing a major depressive episode |
| Interventions | Nitrous oxide Midazolam |
| Duration | Single administration |
| Keywords | Bipolar depression Cerebral blood flow Nitrous oxide Novel therapeutics |
| Key finding | The study is a proof-of-concept trial; no results are reported, but the authors hypothesize that N2O will improve mood and increase frontal cerebral blood flow in bipolar depression. |
Abstract
Depressive symptoms predominate in the course of bipolar disorder (BD) and there is an urgent need to evaluate novel application of repurposed compounds that act on pre-specified treatment targets. Several lines of reasoning suggest that nitrous oxide (N2O) is an ideal medication to study as a potential treatment and as a strategy to identify the underlying pathophysiology of bipolar depression. N2O is a potent cerebral vasodilator and there is compelling evidence of reduced frontal cerebral blood flow (CBF; i.e. hypoperfusion) in depression. Therefore, N2O may increase CBF and thereby improve symptoms of depression. The goal of this randomized, double-blind trial is to study the effect of a single administration of N2O versus the active comparator midazolam on mood and CBF in adults with treatment-resistant bipolar depression. Participants with BD-I/-II currently experiencing a major depressive episode will be randomized to one of two conditions (n = 20/group): 1) inhaled N2O plus intravenous saline, or 2) inhaled room air plus intravenous midazolam. Montgomery-Asberg Depression Rating Scale scores will serve as the primary endpoint. CBF will be measured via arterial spin labelling magnetic resonance imaging. N2O is a potential novel treatment for bipolar depression, as it causes cerebral vasodilation. This proof-of-concept study will provide valuable information regarding the acute impact of N2O on mood and on CBF. If N2O proves to be efficacious in future larger-scale trials, its ubiquity, safety, low cost, and ease of use suggest that it has great potential to become a game-changing acute treatment for bipolar depression.