Mu-Hong Chen1, Cheng-Ta Li2, Wei-Chen Lin3, Chen-Jee Hong1, Pei-Chi Tu4, Ya-Mei Bai5, Chih-Ming Cheng6, Tung-Ping Su7. 1. Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 2. Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. Electronic address: on5083@msn.com. 3. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 4. Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. 5. Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Department of Psychiatry, General Cheng Hsin Hospital, Taipei, Taiwan. Electronic address: tomsu0402@gmail.com.
Abstract
BACKGROUND: A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS:Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life.
RCT Entities:
BACKGROUND: A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0.5mg/kg ketamine, 0.2mg/kg ketamine, and normal saline infusion. Standardized uptake values (SUVs) of glucose metabolism measured through 18F-FDG positron-emission-tomography before infusion and 1day after a 40-min ketamine or normal saline infusion were used for subsequent whole-brain voxel-wise analysis and were correlated with depressive symptoms, as defined using the Hamilton Depression Rating Scale-17 (HDRS-17) score RESULTS: The voxel-wise analysis revealed that patients with TRD receiving the 0.5mg/kg ketamine infusion had significantly higher SUVs (corrected for family-wise errors, P = 0.014) in the supplementary motor area (SMA) and dorsal anterior cingulate cortex (dACC) than did those receiving the 0.2mg/kg ketamine infusion. The increase in the SUV in the dACC was negatively correlated with depressive symptoms at 1day after ketamine infusion DISCUSSION: The persistent antidepressant effect of a 0.5mg/kg ketamine infusion may be mediated by increased activation in the SMA and dACC. The higher increase in dACC activation was related to the reduction in depressive symptoms after ketamine infusion. A 0.5mg/kg ketamine infusion facilitated the glutamatergic neurotransmission in the SMA and dACC, which may be responsible for the persistent antidepressant effect of ketamine much beyond its half-life.
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