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Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology.

ABSTRACT:

Introduction

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.

Methods

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.

Conclusions

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.

SUBMITTER: Dimick MK

PROVIDER: S-EPMC7327241 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology.

Dimick Mikaela K MK Omrin Danielle D MacIntosh Bradley J BJ Mitchell Rachel H B RHB Riegert Daniel D Levitt Anthony A Schaffer Ayal A Belo Susan S Iazzetta John J Detzler Garfield G Choi Mabel M Choi Stephen S Orser Beverley A BA Goldstein Benjamin I BI

Contemporary clinical trials communications 20200623

<h4>Introduction</h4>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 (N<sub>2</sub>O) is an ideal medication to study as a potential treatment and as a strategy to identify the underlying pathophysiology of bipolar depression. N<sub>2</sub>O is a potent cerebral vasodilator and there is compelli ...[more]

PMID: 32637725

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Dataset Information

Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology.

Introduction

Methods

Conclusions

Publications

Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology.

Similar Datasets

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