Erowid References Database
Nagele P, Duma A, Kopec M, Gebara MA, Parsoei A, Walker M, Janski A, Panagopoulous VN, Cristancho P, Miller JP, Zoumski CF, Conway C.
“Nitrous Oxide for Treatment-Resistant Major Depression: a Proof-of-Concept Trial”.
Biological Psychiatry. 2014.
BACKGROUND: NMDA 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 NMDA receptor antagonist, may also be a rapidly acting treatment for TRD.
METHODS: In this blinded, placebo-controlled crossover trial 20 TRD patients were randomized to a 1-hour inhalation of 50 nitrous oxide/50 oxygen or 50 nitrogen/50 oxygen (placebo control). Primary endpoint was the change on HDRS-21 24 hours after treatment.
RESULTS: Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) minutes at a median inspiratory concentration of 44 (37 – 45, IQR). In two patients nitrous oxide treatment was briefly interrupted and in three discontinued. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared to placebo (mean HDRS-21difference at 2 hours: -4.8 points, 95 CI -1.8 to – 7.8 points, p= 0.002; at 24 hours: - 5.5 points, 95 CI -2.5 to -8.5 points, p< 0.001; comparison between nitrous oxide and placebo: p< 0.001). Four patients (20) had treatment response (reduction ≥50 on HDRS); three patients (15) a full remission (HDRS ≤ 7 points) after nitrous oxide, compared to one patient (5) and none after placebo (odds ratio [OR] for response 4.0, 95 CI 0.45 – 35.79; OR for remission 3.0, 95 CI 0.31 – 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 treatment-resistant depression.
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