Treatment-resistant depression(TRD)is a severe psychiatric disorder with a high incidence bringing heavy burden of disease,and better treatment options still need to be explored.In recent years,the antidepressant effects of nitrous oxide(N2O)and its application in TRD have attracted attention.N2O exerts unique rapid onset of action and has comparative advantages in terms of adverse reactions and tolerability and may become a new therapeutic drug for TRD.N2O may exert effects through mechanisms such as antagonizing N-methyl-D-aspartate(NMDA)receptors,regulating serotonin and dopamine,brain-derived neurotrophic factor(BDNF)signaling pathways,and the opioid receptor system.In clinical studies,the efficacy and safety of N2O for TRD have shown promise,displaying advantageous characteristics compared to existing therapies,and the limitations of N2O,such as its side effects,can often be improved via modification of the therapeutic regimen.Future research will mainly focus on validating the long-term efficacy and safety of standardized N2O treatment regimens through larger sample clinical trials,as well as further exploring its individualized or comprehensive treatment,and in-depth neurobiological mechanisms,in order to provide new choices and optimization strategies for clinical treatment practices suitable for relevant populations.

Treatment-resistant depression(TRD)is a severe psychiatric disorder with a high incidence bringing heavy burden of disease,and better treatment options still need to be explored.In recent years,the antidepressant effects of nitrous oxide(N2O)and its application in TRD have attracted attention.N2O exerts unique rapid onset of action and has comparative advantages in terms of adverse reactions and tolerability and may become a new therapeutic drug for TRD.N2O may exert effects through mechanisms such as antagonizing N-methyl-D-aspartate(NMDA)receptors,regulating serotonin and dopamine,brain-derived neurotrophic factor(BDNF)signaling pathways,and the opioid receptor system.In clinical studies,the efficacy and safety of N2O for TRD have shown promise,displaying advantageous characteristics compared to existing therapies,and the limitations of N2O,such as its side effects,can often be improved via modification of the therapeutic regimen.Future research will mainly focus on validating the long-term efficacy and safety of standardized N2O treatment regimens through larger sample clinical trials,as well as further exploring its individualized or comprehensive treatment,and in-depth neurobiological mechanisms,in order to provide new choices and optimization strategies for clinical treatment practices suitable for relevant populations.