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

Mengting Shen, Ye Xuan, Kaiyu Chen, Weiping Lei, Yaqin Huang, Junhui Wang, Jianliang Sun, Xinlei Lu

Drug Design, Development and Therapy October 29, 2025 DOI: 10.2147/dddt.s540781 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, controlled trial Peer reviewed
Sample size 96
Population Female patients aged 18-65 years undergoing unilateral modified radical mastectomy for breast cancer
Interventions Esketamine normal saline
Dose 0.5 mg/kg at induction and 0.25 mg/kg/h during maintenance (esketamine); 5 mL at induction and 0.25 mL/kg/h during maintenance (normal saline)
Duration Perioperative infusion with follow-up to postoperative day 30
Measures Hamilton Depression Rating Scale (HAMD-17), Self-Rating Depression Scale (SDS), brain-derived neurotrophic factor (BDNF), serotonin (5-hydroxytryptamine, 5-HT), heart rate (HR), mean arterial pressure (MAP), Visual Analog Scale (VAS) pain scores
Topics Depression Esketamine Ketamine
Keywords Humans Breast neoplasms Antidepressive agents Infusions, intravenous Double-blind method Adolescent Middle aged Female Young adult Breast cancer Brain-derived neurotrophic factor Pain 5-hydroxytryptamine Perioperative period Postoperative depression
Key findings Perioperative continuous intravenous esketamine lowered postoperative depression scores in breast cancer surgery patients: HAMD-17 on postoperative day 30 was 3.00 (2.08-4.10) with esketamine versus 5.00 (4.00-6.20) with saline, with lower HAMD-17 and SDS scores at earlier time points and higher postoperative BDNF and serotonin levels. Adverse reaction incidence did not differ significantly between groups.

Abstract

Background: 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.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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