Treatment; Nitrous Oxide 50% or 25%, group for Depressive Disorder, Treatment-Resistant
Phase-Based Progress Estimates
Effectiveness
Safety
The Alfred Hospital, Melbourne, Australia
Depressive Disorder, Treatment-Resistant+5 More
Nitrous oxide gas for inhalation - DrugEligibility
18+
All Sexes
What conditions do you have?
Select
Eligibility
18+
All Sexes
What conditions do you have?
Select
Study Summary
To evaluate the acute and sustained antidepressant effects of nitrous oxide in people with major depressive disorder; and further evaluate these effects by identifying the optimal dose and regimen to guide current practice, and to plan a future large pragmatic trial.
Eligible Conditions
- Depressive Disorder, Treatment-Resistant
- Major Depressive Disorder (MDD)
- Unipolar Depression
Treatment Effectiveness
Effectiveness Progress
Other trials for Depressive Disorder, Treatment-Resistant
Study Objectives
1 Primary · 11 Secondary · Reporting Duration: At 24-hours (following treatment-1)
At 24-hours (following treatment-1)
Treatment remission
Treatment response
At Baseline (Prior to treatment-1)
Visual Analog Scale (VAS)
Over 4-weeks (weekly treatment sessions)
Treatment cycle compliance
Over 4-weeks from baseline
Change in HDRS-21 score
Over 7-weeks (length of study participation)
Treatment dose response comparison
Over 7-weeks (length of study participation) from Baseline
Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'anxiety' scores
Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'depression' scores
Changes in Computerize Adaptive Testing - Mental Health (CAT-MH) 'suicide' scores
Suicidal ideation tracking
Over 7-weeks (length of study participation).
Adverse Events
Sustainability of treatment response
Up to 1-week (following treatment-1)
Changes in 'Profile of Mood States' scores
Trial Safety
Safety Progress
This is further along than 68% of similar trials
Other trials for Depressive Disorder, Treatment-Resistant
Trial Design
2 Treatment Groups
Treatment; Nitrous Oxide 50% or 25%, group
1 of 2
Control; Oxygen-air mixture, group
1 of 2
Active Control
Non-Treatment Group
172 Total Participants · 2 Treatment Groups
Primary Treatment: Treatment; Nitrous Oxide 50% or 25%, group · Has Placebo Group · Phase 2
Treatment; Nitrous Oxide 50% or 25%, group
Drug
ActiveComparator Group · 1 Intervention: Nitrous oxide gas for inhalation · Intervention Types: DrugControl; Oxygen-air mixture, group
Drug
PlaceboComparator Group · 1 Intervention: Placebo · Intervention Types: DrugTrial Logistics
Trial Timeline
Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: at 24-hours (following treatment-1)
Closest Location: University of Chicago Medicine · Chicago, IL
2011First Recorded Clinical Trial
1 TrialsResearching Depressive Disorder, Treatment-Resistant
45 CompletedClinical Trials
Who is running the clinical trial?
University of ChicagoLead Sponsor
909 Previous Clinical Trials
726,725 Total Patients Enrolled
The AlfredOTHER
99 Previous Clinical Trials
41,800 Total Patients Enrolled
1 Trials studying Depressive Disorder, Treatment-Resistant
15 Patients Enrolled for Depressive Disorder, Treatment-Resistant
Peter Nagele, MD, MScPrincipal InvestigatorUniversity of Chicago, Department of Anesthesia and Critical Care
2 Previous Clinical Trials
71 Total Patients Enrolled
Paul Myles, MDPrincipal InvestigatorThe Alfred Hospital, Department of Anesthesiology and Perioperative Medicine
1 Previous Clinical Trials
172 Total Patients Enrolled
Eligibility Criteria
Age 18+ · All Participants · 2 Total Inclusion Criteria
Mark “yes” if the following statements are true for you:You have a pre-treatment score of 16 or more on the Hamilton Depression Rating Scale-21 (HDRS-21)
About The Reviewer
Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.
References
- Pałucha-Poniewiera, Agnieszka, and Andrzej Pilc. 2016. “Glutamate-based Drug Discovery for Novel Antidepressants”. Expert Opinion on Drug Discovery. Informa UK Limited. doi:10.1080/17460441.2016.1213234.
- Gerhard, Danielle M., Eric S. Wohleb, and Ronald S. Duman. 2016. “Emerging Treatment Mechanisms for Depression: Focus on Glutamate and Synaptic Plasticity”. Drug Discovery Today. Elsevier BV. doi:10.1016/j.drudis.2016.01.016.
- Mathers, Colin D, and Dejan Loncar. 2006. “Projections of Global Mortality and Burden of Disease from 2002 to 2030”. Edited by Jon Samet. Plos Medicine. Public Library of Science (PLoS). doi:10.1371/journal.pmed.0030442.
- Zaffina, S., M. Lembo, F. Gilardi, A. Bussu, F. Pattavina, M. G. Tucci, U. Moscato, et al.. 2019. “Nitrous Oxide Occupational Exposure in Conscious Sedation Procedures in Dental Ambulatories: A Pilot Retrospective Observational Study in an Italian Pediatric Hospital”. BMC Anesthesiology. Springer Science and Business Media LLC. doi:10.1186/s12871-019-0714-x.
- Furukawa, Toshi A., Tatsuo Akechi, Hideki Azuma, Toru Okuyama, and Teruhiko Higuchi. 2007. “Evidence-based Guidelines for Interpretation of the Hamilton Rating Scale for Depression”. Journal of Clinical Psychopharmacology. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/jcp.0b013e31814f30b1.
- Conway, Charles R., Mark S. George, and Harold A. Sackeim. 2017. “Toward an Evidence-based, Operational Definition of Treatment-resistant Depression”. JAMA Psychiatry. American Medical Association (AMA). doi:10.1001/jamapsychiatry.2016.2586.
- Nagele, P., L. B. Metz, and C. M. Crowder. 2004. “Nitrous Oxide (N 2 O) Requires the n -methyl- d -aspartate Receptor for Its Action in caenorhabditis Elegans”. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.0402825101.
- Nagele, Peter, Frank Brown, Amber Francis, Mitchell G. Scott, Brian F. Gage, and J. Philip Miller. 2013. “Influence of Nitrous Oxide Anesthesia, B-vitamins, Andmthfrgene Polymorphisms on Perioperative Cardiac Events”. Anesthesiology. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/aln.0b013e31829761e3.
- Caddy, Caroline, Giovanni Giaroli, Thomas P. White, Sukhwinder S. Shergill, and Derek K. Tracy. 2013. “Ketamine as the Prototype Glutamatergic Antidepressant: Pharmacodynamic Actions, and a Systematic Review and Meta-analysis of Efficacy”. Therapeutic Advances in Psychopharmacology. SAGE Publications. doi:10.1177/2045125313507739.
- Myles, Paul S., Kate Leslie, Matthew T. V. Chan, Andrew Forbes, Michael J. Paech, Philip Peyton, Brendan S. Silbert, Elaine Pascoe, and the ENIGMA Trial Group. 2007. “Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery”. Anesthesiology. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/01.anes.0000270723.30772.da.
- Katalinic, Natalie, Rosalyn Lai, Andrew Somogyi, Philip B Mitchell, Paul Glue, and Colleen K Loo. 2013. “Ketamine as a New Treatment for Depression: A Review of Its Efficacy and Adverse Effects”. Australian & New Zealand Journal of Psychiatry. SAGE Publications. doi:10.1177/0004867413486842.
- Morgan, Celia J. A., H. Valerie Curran, and the Independent Scientific Committee on Drugs (ISCD). 2011. “Ketamine Use: A Review”. Addiction. Wiley. doi:10.1111/j.1360-0443.2011.03576.x.
- Hu, Y.-D., Y.-T. Xiang, J.-X. Fang, S. Zu, S. Sha, H. Shi, G. S. Ungvari, et al.. 2015. “Single I.v. Ketamine Augmentation of Newly Initiated Escitalopram for Major Depression: Results from a Randomized, Placebo-controlled 4-week Study”. Psychological Medicine. Cambridge University Press (CUP). doi:10.1017/s0033291715002159.
- Iadarola, Nicolas D., Mark J. Niciu, Erica M. Richards, Jennifer L. Vande Voort, Elizabeth D. Ballard, Nancy B. Lundin, Allison C. Nugent, Rodrigo Machado-Vieira, and Carlos A. Zarate Jr. 2015. “Ketamine and Other N-methyl-d-aspartate Receptor Antagonists in the Treatment of Depression: A Perspective Review”. Therapeutic Advances in Chronic Disease. SAGE Publications. doi:10.1177/2040622315579059.
- Morgan, Celia J. A., and H. Valerie Curran. 2006. “Acute and Chronic Effects of Ketamine Upon Human Memory: A Review”. Psychopharmacology. Springer Science and Business Media LLC. doi:10.1007/s00213-006-0572-3.
- Kyle, Phillip Raphael, Ole Michael Lemming, Nina Timmerby, Susan Søndergaard, Kate Andreasson, and Per Bech. 2016. “The Validity of the Different Versions of the Hamilton Depression Scale in Separating Remission Rates of Placebo and Antidepressants in Clinical Trials of Major Depression”. Journal of Clinical Psychopharmacology. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/jcp.0000000000000557.
- Nagele, Peter, Andreas Duma, Michael Kopec, Marie Anne Gebara, Alireza Parsoei, Marie Walker, Alvin Janski, et al.. 2015. “Nitrous Oxide for Treatment-resistant Major Depression: A Proof-of-concept Trial”. Biological Psychiatry. Elsevier BV. doi:10.1016/j.biopsych.2014.11.016.
- Goldberg, Joseph F., and Martin Harrow. 2005. “Subjective Life Satisfaction and Objective Functional Outcome in Bipolar and Unipolar Mood Disorders: A Longitudinal Analysis”. Journal of Affective Disorders. Elsevier BV. doi:10.1016/j.jad.2005.08.008.
- Sanders, Robert D., Jörg Weimann, Mervyn Maze, David S. Warner, and Mark A. Warner. 2008. “Biologic Effects of Nitrous Oxide”. Anesthesiology. Ovid Technologies (Wolters Kluwer Health). doi:10.1097/aln.0b013e3181870a17.
- Djulbegovic, Benjamin, Iztok Hozo, and John P. A. Ioannidis. 2014. “Improving the Drug Development Process”. Jama. American Medical Association (AMA). doi:10.1001/jama.2013.283742.
- Myles, Paul S, Kate Leslie, Matthew T V Chan, Andrew Forbes, Philip J Peyton, Michael J Paech, W Scott Beattie, et al.. 2014. “The Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery (ENIGMA-II): A Randomised, Single-blind Trial”. The Lancet. Elsevier BV. doi:10.1016/s0140-6736(14)60893-x.
- McIntyre, Roger S., Marie-Josée Filteau, Lawrence Martin, Simon Patry, Andre Carvalho, Danielle S. Cha, Maxime Barakat, and Maia Miguelez. 2014. “Treatment-resistant Depression: Definitions, Review of the Evidence, and Algorithmic Approach”. Journal of Affective Disorders. Elsevier BV. doi:10.1016/j.jad.2013.10.043.
- McCloud TL, Caddy C, Jochim J, Rendell JM, Diamond PR, Shuttleworth C, Brett D, Amit BH, McShane R, Hamadi L, Hawton K, Cipriani A. Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. Cochrane Database Syst Rev. 2015 Sep 29;(9):CD011611. doi: 10.1002/14651858.CD011611.pub2. Review. Update in: Cochrane Database Syst Rev. 2021 Oct 8;10:CD011611.
- Lenze, Eric J., Nuri B. Farber, Evan Kharasch, Julie Schweiger, Michael Yingling, John Olney, and John W. Newcomer. 2016. “Ninety-six Hour Ketamine Infusion with Co-administered Clonidine for Treatment-resistant Depression: A Pilot Randomised Controlled Trial”. The World Journal of Biological Psychiatry. Informa UK Limited. doi:10.3109/15622975.2016.1142607.
- Lener, Marc S., Mark J. Niciu, Elizabeth D. Ballard, Minkyung Park, Lawrence T. Park, Allison C. Nugent, and Carlos A. Zarate Jr.. 2017. “Glutamate and Gamma-aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine”. Biological Psychiatry. Elsevier BV. doi:10.1016/j.biopsych.2016.05.005.
- Autry, Anita E., Megumi Adachi, Elena Nosyreva, Elisa S. Na, Maarten F. Los, Peng-fei Cheng, Ege T. Kavalali, and Lisa M. Monteggia. 2011. “NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses”. Nature. Springer Science and Business Media LLC. doi:10.1038/nature10130.
- Zorumski, Charles F., Peter Nagele, Steven Mennerick, and Charles R. Conway. 2015. “Treatment-resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy”. Frontiers in Psychiatry. Frontiers Media SA. doi:10.3389/fpsyt.2015.00172.
- Gibbons, Robert D., David J. Weiss, Paul A. Pilkonis, Ellen Frank, Tara Moore, Jong Bae Kim, and David J. Kupfer. 2012. “Development of a Computerized Adaptive Test for Depression”. Archives of General Psychiatry. American Medical Association (AMA). doi:10.1001/archgenpsychiatry.2012.14.
- Gibbons, Robert D., David Kupfer, Ellen Frank, Tara Moore, David G. Beiser, and Edwin D. Boudreaux. 2017. “Development of a Computerized Adaptive Test Suicide Scale—the CAT-SS”. The Journal of Clinical Psychiatry. Physicians Postgraduate Press, Inc. doi:10.4088/jcp.16m10922.
- Kim, Yong-Ku, and Kyoung-Sae Na. 2016. “Role of Glutamate Receptors and Glial Cells in the Pathophysiology of Treatment-resistant Depression”. Progress in Neuro-psychopharmacology and Biological Psychiatry. Elsevier BV. doi:10.1016/j.pnpbp.2016.03.009.
- Ueno, Fumihiko, Shinichiro Nakajima, Takefumi Suzuki, Takayuki Abe, Yuji Sato, Masaru Mimura, and Hiroyuki Uchida. 2015. “Whether to Increase or Maintain Dosage of Mirtazapine in Early Nonimprovers with Depression”. The Journal of Clinical Psychiatry. Physicians Postgraduate Press, Inc. doi:10.4088/jcp.14m09201.
- Kavalali, Ege T, and Lisa M Monteggia. 2015. “How Does Ketamine Elicit a Rapid Antidepressant Response?”. Current Opinion in Pharmacology. Elsevier BV. doi:10.1016/j.coph.2014.11.005.
- Snaith, R. P.. 1996. “Present Use of the Hamilton Depression Rating Scale: Observations on Method of Assessment in Research of Depressive Disorders”. British Journal of Psychiatry. Royal College of Psychiatrists. doi:10.1192/bjp.168.5.594.
- Levkovitz, Yechiel, Moshe Isserles, Frank Padberg, Sarah H. Lisanby, Alexander Bystritsky, Guohua Xia, Aron Tendler, et al.. 2015. “Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Major Depression: A Prospective Multicenter Randomized Controlled Trial”. World Psychiatry. Wiley. doi:10.1002/wps.20199.
- Leucht, Stefan, Hein Fennema, Rolf Engel, Marion Kaspers–Janssen, Peter Lepping, and Armin Szegedi. 2013. “What Does the HAMD Mean?”. Journal of Affective Disorders. Elsevier BV. doi:10.1016/j.jad.2012.12.001.
- Schlaepfer, Thomas E, Hans Ågren, Palmiero Monteleone, Cristobal Gasto, William Pitchot, Frederick Rouillon, David J Nutt, and Siegfried Kasper. 2012. “The Hidden Third: Improving Outcome in Treatment-resistant Depression”. Journal of Psychopharmacology. SAGE Publications. doi:10.1177/0269881111431748.
- 2021. "Antidepressant Effects of Nitrous Oxide". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05357040.
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