Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology
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 st...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
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| Series: | Contemporary Clinical Trials Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2451865420300843 |
| _version_ | 1818400119134879744 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mikaela K. Dimick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T07:31:30Z |
| format | Article |
| id | doaj.art-94973429d91347ab9a5579e7f6f07db3 |
| institution | Directory Open Access Journal |
| issn | 2451-8654 |
| language | English |
| last_indexed | 2024-12-14T07:31:30Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Contemporary Clinical Trials Communications |
| spelling | doaj.art-94973429d91347ab9a5579e7f6f07db32022-12-21T23:11:22ZengElsevierContemporary Clinical Trials Communications2451-86542020-09-0119100600Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodologyMikaela K. Dimick0Danielle Omrin1Bradley J. MacIntosh2Rachel H.B. Mitchell3Daniel Riegert4Anthony Levitt5Ayal Schaffer6Susan Belo7John Iazzetta8Garfield Detzler9Mabel Choi10Stephen Choi11Beverley A. Orser12Benjamin I. Goldstein13Pharmacology and Toxicology Department, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Pharmacy Department, Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, CanadaSunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, CanadaPharmacology and Toxicology Department, University of Toronto, Toronto, Ontario, Canada; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Corresponding authorCentre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5 T, Canada.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.http://www.sciencedirect.com/science/article/pii/S2451865420300843Nitrous oxideBipolar depressionNovel therapeuticsCerebral blood flow |
| spellingShingle | 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 Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology Contemporary Clinical Trials Communications Nitrous oxide Bipolar depression Novel therapeutics Cerebral blood flow |
| title | Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology |
| title_full | Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology |
| title_fullStr | Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology |
| title_full_unstemmed | Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology |
| title_short | Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: Proof-of-concept study design and methodology |
| title_sort | nitrous oxide as a putative novel dual mechanism treatment for bipolar depression proof of concept study design and methodology |
| topic | Nitrous oxide Bipolar depression Novel therapeutics Cerebral blood flow |
| url | http://www.sciencedirect.com/science/article/pii/S2451865420300843 |
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