TY - JOUR
T1 - Nitrous oxide for treatment-resistant major depression
T2 - A proof-of-concept trial
AU - Nagele, Peter
AU - Duma, Andreas
AU - Kopec, Michael
AU - Gebara, Marie Anne
AU - Parsoei, Alireza
AU - Walker, Marie
AU - Janski, Alvin
AU - Panagopoulos, Vassilis N.
AU - Cristancho, Pilar
AU - Miller, J. Philip
AU - Zorumski, Charles F.
AU - Conway, Charles R.
N1 - Funding Information:
PN has filed for intellectual property protection related to the use of nitrous oxide in major depression and has received research support from Roche Diagnostics, Abbot, and Express Scripts unrelated to this work. CFZ serves on the Scientific Advisory Board of Sage Therapeutics; Sage Therapeutics was not involved in this study. CC was previously on the speaker’s bureau for Bristol-Myers Squibb and Otsuka Pharmaceuticals and has received research funding from Bristol-Myers Squibb, Cyberonics, the Stanley Baer Foundation, and the Brain and Behavior Research Foundation. All other authors report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2015 Society of Biological Psychiatry.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: N-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. METHODS: In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. RESULTS: Mean duration of nitrous oxide treatment was 55.6 6 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, 24.8 points, 95% confidence interval [CI], 21.8 to 27.8 points, p =.002; at 24 hours, 25.5 points, 95% CI, 22.5 to 28.5 points, p <.001; comparison between nitrous oxide and placebo, p <.001). Four patients (20%) had treatment response (reduction ≥50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 ≤ 7 points) after nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI,.45-35.79; OR for remission, 3.0, 95% CI,.31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. CONCLUSIONS: This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.
AB - BACKGROUND: N-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. METHODS: In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. RESULTS: Mean duration of nitrous oxide treatment was 55.6 6 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, 24.8 points, 95% confidence interval [CI], 21.8 to 27.8 points, p =.002; at 24 hours, 25.5 points, 95% CI, 22.5 to 28.5 points, p <.001; comparison between nitrous oxide and placebo, p <.001). Four patients (20%) had treatment response (reduction ≥50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 ≤ 7 points) after nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI,.45-35.79; OR for remission, 3.0, 95% CI,.31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. CONCLUSIONS: This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.
KW - Major depression
KW - Nitrous oxide
KW - Treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=84939803581&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2014.11.016
DO - 10.1016/j.biopsych.2014.11.016
M3 - Article
C2 - 25577164
AN - SCOPUS:84939803581
SN - 0006-3223
VL - 78
SP - 10
EP - 18
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 1
ER -