Mingqia Wang1,2, Bin Zhang3,4, Yangling Zhou1,2, Chengyu Wang1,2, Wei Zheng1,2, Weijian Liu1,2, Yanni Zhan1,2, Xiaofeng Lan1,2, Yuping Ning1,2. 1. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. 2. Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China. 3. The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China. zhang.bin845@gzhmu.edu.cn. 4. Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China. zhang.bin845@gzhmu.edu.cn.
Abstract
RATIONALE: Recently, the effects of ketamine on the circadian rhythm have suggested that ketamine's rapid antidepressant effects are associated with and without sleep disturbance improvement. OBJECTIVES: Here, we evaluated the antidepressant efficacy of repeated ketamine infusions in patients with sleep disturbances. METHODS: This study included 127 patients with major depressive disorder or bipolar disorder who received ketamine treatments during a 12-day period. Sleep quality was assessed by the 17-item Hamilton Depression Rating Scale sleep disturbance factor (SDF) (items 4, 5 and 6). Serum brain-derived neurotrophic factor (BDNF) was measured at baseline, day 13 and day 26. This study was a post-hoc analysis. RESULTS: Significant differences were found in the HAMD-17 score at 13 post-infusion time points compared to baseline, as well as the scores in SDF score at each of the 7 post-infusion (4 h after each infusion excluded) time points among all patients. Logistic regression and linear correlation analyses revealed that a greater reduction in the SDF after 24 h of the first ketamine infusion resulted in a better antidepressant effect in the last two follow-up visits. Moreover, BDNF levels were significantly higher in sleep responders than in non-responders. CONCLUSIONS: In the 127 patients, six ketamine infusions induced better therapeutic effects in sleep responders than in sleep non-responders and patients without sleep disturbances. The sleep response after repeated ketamine infusions was positively associated with high serum BDNF levels. Early sleep disturbance improvement (as early as 24 h after the first ketamine injection) may predict the antidepressant effect of repeated-dose ketamine.
RATIONALE: Recently, the effects of ketamine on the circadian rhythm have suggested that ketamine's rapid antidepressant effects are associated with and without sleep disturbance improvement. OBJECTIVES: Here, we evaluated the antidepressant efficacy of repeated ketamine infusions in patients with sleep disturbances. METHODS: This study included 127 patients with major depressive disorder or bipolar disorder who received ketamine treatments during a 12-day period. Sleep quality was assessed by the 17-item Hamilton Depression Rating Scale sleep disturbance factor (SDF) (items 4, 5 and 6). Serum brain-derived neurotrophic factor (BDNF) was measured at baseline, day 13 and day 26. This study was a post-hoc analysis. RESULTS: Significant differences were found in the HAMD-17 score at 13 post-infusion time points compared to baseline, as well as the scores in SDF score at each of the 7 post-infusion (4 h after each infusion excluded) time points among all patients. Logistic regression and linear correlation analyses revealed that a greater reduction in the SDF after 24 h of the first ketamine infusion resulted in a better antidepressant effect in the last two follow-up visits. Moreover, BDNF levels were significantly higher in sleep responders than in non-responders. CONCLUSIONS: In the 127 patients, six ketamine infusions induced better therapeutic effects in sleep responders than in sleep non-responders and patients without sleep disturbances. The sleep response after repeated ketamine infusions was positively associated with high serum BDNF levels. Early sleep disturbance improvement (as early as 24 h after the first ketamine injection) may predict the antidepressant effect of repeated-dose ketamine.
Entities:
Keywords:
Antidepressant efficacy; Bipolar disorder; Brain-derived neurotrophic factor; Early prediction; HAMD-17; Ketamine; Major depressive disorder; Sleep disturbance; Sleep improvement
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