Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial
Objective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Psiquiatria (ABP)
2021-02-01
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| Series: | Brazilian Journal of Psychiatry |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462021000500484&tlng=en |
| _version_ | 1818947169830305792 |
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| author | Mara C. Guimarães Tiago M. Guimarães Jaime E. Hallak João Abrão João P. Machado-de-Sousa |
| author_facet | Mara C. Guimarães Tiago M. Guimarães Jaime E. Hallak João Abrão João P. Machado-de-Sousa |
| author_sort | Mara C. Guimarães |
| collection | DOAJ |
| description | Objective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. Methods: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. Results: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. Conclusion: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. Clinical trial registration: Brazilian Register of Clinical Trials, RBR-5rz5ch |
| first_indexed | 2024-12-20T08:26:38Z |
| format | Article |
| id | doaj.art-873f30f7809a4d1986ae7bd179f00f12 |
| institution | Directory Open Access Journal |
| issn | 1809-452X |
| language | English |
| last_indexed | 2024-12-20T08:26:38Z |
| publishDate | 2021-02-01 |
| publisher | Associação Brasileira de Psiquiatria (ABP) |
| record_format | Article |
| series | Brazilian Journal of Psychiatry |
| spelling | doaj.art-873f30f7809a4d1986ae7bd179f00f122022-12-21T19:46:48ZengAssociação Brasileira de Psiquiatria (ABP)Brazilian Journal of Psychiatry1809-452X2021-02-0143548449310.1590/1516-4446-2020-1543Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trialMara C. Guimarãeshttps://orcid.org/0000-0002-6531-1921Tiago M. Guimarãeshttps://orcid.org/0000-0001-6384-9886Jaime E. HallakJoão AbrãoJoão P. Machado-de-SousaObjective: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. Methods: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. Results: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. Conclusion: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. Clinical trial registration: Brazilian Register of Clinical Trials, RBR-5rz5chhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462021000500484&tlng=ennitrous oxidemajor depressive disorderglutamatergic systemNMDA receptor |
| spellingShingle | Mara C. Guimarães Tiago M. Guimarães Jaime E. Hallak João Abrão João P. Machado-de-Sousa Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial Brazilian Journal of Psychiatry nitrous oxide major depressive disorder glutamatergic system NMDA receptor |
| title | Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial |
| title_full | Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial |
| title_fullStr | Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial |
| title_full_unstemmed | Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial |
| title_short | Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial |
| title_sort | nitrous oxide as an adjunctive therapy in major depressive disorder a randomized controlled double blind pilot trial |
| topic | nitrous oxide major depressive disorder glutamatergic system NMDA receptor |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462021000500484&tlng=en |
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