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Potential Pathways Involved in the Rapid Antidepressant Effects of Nitrous Oxide

2015; Elsevier BV; Volume: 78; Issue: 1 Linguagem: Inglês

10.1016/j.biopsych.2015.04.007

1873-2402

Carlos A. Zarate, Rodrigo Machado‐Vieira,

Intensive Care Unit Cognitive Disorders

Studies that evaluate agents with potentially rapid antidepressant effects are critical to developing new, improved treatments for major mood disorders. In particular, such studies may offer key insights into the mechanism of action of rapid-acting antidepressants as well as the neurobiology of mood disorders ( 1 Machado-Vieira R. Salvadore G. Luckenbaugh D.A. Manji H.K. Zarate Jr, C.A. Rapid onset of antidepressant action: A new paradigm in the research and treatment of major depressive disorder. J Clin Psychiatry. 2008; 69: 946-958 Crossref PubMed Scopus (162) Google Scholar ). In their excellent article published in this issue of Biological Psychiatry, Nagele et al. ( 2 Nagele P. Duma A. Kopec M. Gebara M.A. Parsoei A. Walker M. et al. Nitrous oxide for treatment-resistant major depression: A proof-of-concept trial. Biol Psychiatry. 2015; 78: 10-18 Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar ) investigated the antidepressant effects of nitrous oxide (N2O), largely because its mechanism of action is similar to the mechanism of action of the N-methyl-D-aspartate (NMDA) antagonist ketamine. Multiple studies found that subanesthetic doses of ketamine have rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder and bipolar disorder ( 1 Machado-Vieira R. Salvadore G. Luckenbaugh D.A. Manji H.K. Zarate Jr, C.A. Rapid onset of antidepressant action: A new paradigm in the research and treatment of major depressive disorder. J Clin Psychiatry. 2008; 69: 946-958 Crossref PubMed Scopus (162) Google Scholar ). In this blinded, placebo-controlled, crossover trial, 20 patients with treatment-resistant depression were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control) ( 2 Nagele P. Duma A. Kopec M. Gebara M.A. Parsoei A. Walker M. et al. Nitrous oxide for treatment-resistant major depression: A proof-of-concept trial. Biol Psychiatry. 2015; 78: 10-18 Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar ). Compared with placebo, nitrous oxide significantly reduced depressive symptoms at 2 hours and 24 hours. Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept TrialBiological PsychiatryVol. 78Issue 1PreviewN-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. Full-Text PDF Open Access