Autophagy: A New Mechanism for Esketamine as a Depression Therapeutic

Jiang, Guanghao; Wang, Yibo; Liu, Qingzhen; Gu, Tingting; Liu, Suting; Yin, Anqi; Zhang, Lidong

doi:10.1016/j.neuroscience.2022.05.014

Cited by 21 publications

(12 citation statements)

References 35 publications

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Section: Discussionmentioning

confidence: 99%

“…[25] In addition, a recent animal experiment showed that esketamine could inhibit autophagy through mTOR-BDNF signaling, thus reducing neuroinflammation induced by lipopolysaccharide, mainly decreasing inflammation-related cytokines (TNF-, IL-1, IL-6), apoptotic factors and autophagic marker levels, to deliver antidepressant effects. [26] As an anesthetic drug, esketamine has been used for many years, but there were no sufficient data for the prevention or treatment of psychiatric disorders. Considering the possible risk of hallucinogenic effects and abuse of esketamine, the dose used in this study was slightly lower than the subanesthetic dose, and esketamine was only injected intravenously once.…”

Section: Antidepressant Effect Of Esketaminementioning

confidence: 99%

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Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial

et al. 2023

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Background: To evaluate the effect of pre-administration of esketamine intraoperatively on the occurrence of postpartum depression after cesarean section under combined spinal-epidural anesthesia. Methods: A total of 120 women aged 24 to 36 years undergoing cesarean section by spinal-epidural anesthesia with American Society of Anesthesiologists physical status II were enrolled. According to the intraoperative use of esketamine, all participants were randomly divided into 2 groups: test group (group E) and control group (group C). Esketamine was administered intravenously at a dose of 0.2 mg/kg after the infant was delivered in group E and equal volume of normal saline was given in group C. The incidence of postpartum depression was recorded at 1 week and 6 weeks after the operation. The occurrence of adverse reactions such as postpartum bleeding, nausea and vomiting, drowsiness, and nightmares were also recorded at 48 hours after surgery. Results: Compared with group C, the incidence of postpartum depression was significantly lower at 1 week and 6 weeks after surgery in group E (P < .01). There was no significant difference of the adverse effects at 48 hours after the operation between the 2 groups. Conclusion: Intravenous infusion of 0.2 mg/kg esketamine in women during cesarean section can significantly reduce the incidence of postpartum depression at 1 week and 6 weeks after surgery without increasing related adverse effects.

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Section: Discussionmentioning

confidence: 99%

Section: Antidepressant Effect Of Esketaminementioning

confidence: 99%

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial

et al. 2023

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“…Rawat et al revealed that the activation of immature granule neurons in the dentate gyrus of hippocampus was necessary and sufficient for the antidepressant effect of ketamine ( 35 ). In lipopolysaccharide-induced depression mice models, esketamine conveyed antidepressant effects by inhibiting autophagy via the mTOR- brain-derived neurotrophic factor (BDNF) pathway ( 36 ). For mice subjected to abdominal surgery, esketamine alleviated postoperative depression-like behaviors by inhibiting inflammatory effects in the prefrontal cortex ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

“…granule neurons in the dentate gyrus of hippocampus was necessary and sufficient for the antidepressant effect of ketamine (35). In lipopolysaccharide-induced depression mice models, esketamine conveyed antidepressant effects by inhibiting autophagy via the mTOR-brain-derived neurotrophic factor (BDNF) pathway (36).…”

Section: Discussionmentioning

confidence: 99%

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

et al. 2023

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BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = −10.5, 95%CI = −19.6% to −0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = −10.8, 95%CI = −20.2% to −0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).

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“…[22] In this study, group E did not use opioids, with the aim to avoid the release of inflammatory factors from immune cells stimulated by opioids, while esketamine may have the same anti-inflammatory effect as ketamine, [23,24] so the levels of inflammatory factors IL-6, IL-8, CRP, or TNF-α at T1, T2, T3, and T4 were lower than in group C. In an animal model of depression, ESK inhibited lipopolysaccharide-induced neuroinflammation, and the levels of pro-inflammatory cytokines (including TNF-α, IL-6, and IL-1β) increased after lipopolysaccharide administration, which was reversed after 7 days of ESK treatment. [25] ESK, the S-enantiomer of ketamine, has a higher affinity for N-methyl-D-aspartate receptor [26] and is twice as effective as ketamine. PCIA with ESK (0.01 mg/kg/hour) as an adjuvant can significantly reduce the incidence of postpartum depression within 14 days and relieve pain within 48 hours after cesarean section without increasing the incidence of adverse reactions.…”

Section: Discussionmentioning

confidence: 99%

Effect of esketamine on inflammatory factors in opioid-free anesthesia based on quadratus lumborum block: A randomized trial

Dai,

Li,

Zheng

et al. 2023

Medicine

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Background: As strong analgesics, opioids provide the analgesic component of general anesthesia, but they have bidirectional effects on the immune system, promoting the production of pro-inflammatory factors. The idea of opioid-free anesthesia is to replace the analgesic effect of opioids in the treatment of acute pain with comparably effective drugs that do not affect the immune system and thereby decrease the production of inflammatory factors. Therefore, this study aims to observe the effect of opioid-free esketamine anesthesia based on quadratus lumborum block on inflammatory factors in patients undergoing lower abdominal or pelvic surgery. Methods: A total of 122 patients who underwent lower abdominal or pelvic surgery in our hospital from March 2021 to June 2022 were selected and divided into the esketamine (E) group (n = 62) and control (C) group (n = 60) according to the random number table method. According to the surgical field, the 2 groups underwent unilateral/bilateral quadratus lumborum block in the supine position under ultrasound guidance. In addition, both groups received a target controlled infusion of propofol 3 to 3.5 μg/mL and intravenous rocuronium 0.8 mg/kg. Group E was given opioid-free anesthesia, group C was given opioid-based anesthesia. A 3 to 5 laryngeal mask was inserted according to body weight, and rocuronium 0.5 mg/kg was added intermittently. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP), procalcitonin, tumor necrosis factor-α (TNF-α), numeric rating scales, dosage of propofol, dexmedetomidine and rocuronium, as well as the numeric rating scales score and analgesic complications were monitored in the 2 groups. Results: There was no significant differences in general outcomes between the 2 groups (P > .05). The blood pressure in group E was higher than in group C at T1 (P < .05). The levels of IL-6, TNF-α, CRP and IL-8 in group E were significantly lower than in group C at T1, T2, T3, and T4 (P < .05). The levels of IL-6, TNF-α, procalcitonin, CRP and IL-8 in the 2 groups at T1, T2, T3, and T4 were significantly higher than at T0 (P < .05). Conclusion: Opioid-free esketamine anesthesia based on quadratus lumborum block achieved perfect postoperative analgesia with little effect on inflammatory factors in patients undergoing lower abdominal or pelvic surgery.

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Autophagy: A New Mechanism for Esketamine as a Depression Therapeutic

Cited by 21 publications

References 35 publications

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

Effect of esketamine on inflammatory factors in opioid-free anesthesia based on quadratus lumborum block: A randomized trial

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