DISCUSSION
TRD, ideation, tumor necrosis, depressive disorder, depressive, depression
DISEASE, TUMOR NECROSIS
Our results suggest that the antidepressant effect of low-dose ketamine infusion persists for 14 days in patients with TRD and prominent suicidal ideation. However, based on clinician-rated and self-reported measures, the antisuicidal effect of the ketamine infusion may diminish after 5–7 days. Additionally, our study highlights how treatment timing influences the antidepressant and antisuicidal effects of low-dose ketamine; only patients with moderate or low treatment refractoriness, those whose current depressive episode had lasted <24 months, and those with ≤4 failed antidepressant treatments benefited from the low-dose ketamine infusion.Previous studies have investigated the associations between treatment refractoriness and the response to conventional antidepressants, prefrontal theta-burst stimulation (TBS), and electroconvulsive therapy (Treatment refractoriness lies on a clinical spectrum; refractoriness may include the failure of 3 antidepressants to that of all available antidepressants, depressive episodes lasting 6 months to more than 2 years, and response or resistance to neurostimulation (Based on our findings, we propose the following 2 clinical recommendations. First, clinicians should optimize their timing of low-dose ketamine treatment from patients with TRD on the basis of the disease and treatment course. Specifically, patients experiencing depressive episodes that have persisted ≥12 but <24 months or who have failed to respond to >2 but ≤4 antidepressants may benefit the most from ketamine infusion. Second, our previous study suggested that the symptoms of clinical depression can be ameliorated by biweekly ketamine infusion but that the inflammatory profiles of interleukin-2 and tumor necrosis factor-α may be improved more by weekly infusion (Our application of the PANSI-PSI and PANSI-NSI may help to clarify the effect of low-dose ketamine on suicidal symptoms (Finally, the inpatient setting was conducted in previous esketamine or ketamine clinical trials of patients with major depressive disorder and suicidal thoughts (Our study has several limitations. First, we examined ketamine as an add-on medication, meaning that the other medications used by the patients with TRD were not discontinued during the study period. The add-on study design is ethically appropriate for patients with TRD and prominent suicidal ideation and may provide more realistic data. Second, we administered only a single ketamine infusion to each patient. Further studies using repeated infusions of low-dose ketamine are warranted to examine the sustained antidepressant and antisuicidal effects of ketamine in patients with severe depression and suicidal ideation.