Effects of Continuous Perioperative Esketamine Infusion on Postoperative Depression in Breast Cancer Patients: A Randomized Controlled Double-Blind Trial

Mengting Shen,1,2 Ye Xuan,1,2 Kaiyu Chen,1,2 Weiping Lei,2 Yaqin Huang,2 Junhui Wang,3 Jianliang Sun,1,2,* Xinlei Lu2,* 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, People’s Republic of China; 3Affiliated Luqiao Hospital, HangZhou City University School of Medicine, Taizhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianliang Sun, Email [email protected] Xinlei Lu, Email [email protected]: Comorbid depressive symptoms are prevalent in patients with breast cancer, which adversely impacts postoperative recovery outcomes. Esketamine has emerged as a promising intervention for perioperative depression due to its rapid and sustained effects. This study aims to investigate the impact of the continuous intravenous infusion of esketamine during the perioperative period on postoperative depressive symptoms in breast cancer patients.Methods: In this randomized, double-blind, controlled trial, 96 female patients aged 18– 65 years undergoing unilateral modified radical mastectomy were enrolled. Participants were randomly assigned to one of two groups. The esketamine group received 0.5 mg/kg and 0.25 mg/kg/h esketamine and the normal saline group received 5 mL and 0.25 mL/kg/h normal saline during anesthesia induction and maintenance, respectively. The primary outcome was the Hamilton Depression Rating Scale (HAMD-17) score on postoperative day 30 (POD-30). Secondary outcomes included HAMD-17 scores on POD 1 and 3; self-Rating Depression Scale (SDS) scores on POD 1, 3, and 30; serum levels of brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) after surgery; relative changes in heart rate (HR) and mean arterial pressure (MAP) before and after intubation; time to awakening; Visual Analog Scale (VAS) pain scores; and adverse events related to esketamine.Results: The HAMD-17 score on POD-30 was significantly lower in the esketamine group [3.00 (2.08– 4.10)] than in the normal saline group [5.00 (4.00– 6.20)]. Regarding secondary outcomes, HAMD-17 scores on POD 1 and 3 were significantly lower in the esketamine group. SDS scores on POD 1, 3, and 30 were also significantly lower in the esketamine group. Compared with the saline group, the esketamine group exhibited significantly higher postoperative levels of BDNF and serotonin. Additionally, VAS scores at 30 minutes after extubation were significantly lower in the esketamine group. There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion: Perioperative continuous administration of esketamine reduces postoperative depression scores in patients undergoing breast cancer surgery.Trial Registration: Chinese Clinical Trial Registry. Identifier: ChiCTR2200061575.Keywords: esketamine, perioperative period, breast cancer, postoperative depression, brain-derived neurotrophic factor, 5-hydroxytryptamine, pain