Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial

被引:161
作者
Nagele, Peter [1 ,3 ]
Duma, Andreas [1 ]
Kopec, Michael [1 ]
Gebara, Marie Anne [2 ]
Parsoei, Alireza [2 ]
Walker, Marie [2 ]
Janski, Alvin [2 ]
Panagopoulos, Vassilis N. [2 ]
Cristancho, Pilar [2 ]
Miller, J. Philip [4 ]
Zorumski, Charles F. [2 ,3 ]
Conway, Charles R. [2 ,3 ]
机构
[1] Washington Univ, Sch Med, Dept Anesthesiol, Div Clin & Translat Res, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Taylor Family Inst Innovat Psychiat Res, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
关键词
Major depression; Nitrous oxide; Treatment-resistant depression; D-ASPARTATE ANTAGONIST; ANTINOCICEPTIVE RESPONSE; ANTIDEPRESSANT RESPONSE; ALCOHOL DEPENDENCE; RANDOMIZED-TRIAL; NMDA ANTAGONIST; FAMILY-HISTORY; KETAMINE; RECEPTOR; MECHANISMS;
D O I
10.1016/j.biopsych.2014.11.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 +/- 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, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 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.
引用
收藏
页码:10 / 18
页数:9
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