An Intraoperative Sub-Anesthetic Dose of Esketamine on Postoperative Depressive Symptoms in Perimenopausal Women with Breast Cancer Undergoing Modified Radical Mastectomy: Protocol for a Randomized, Triple-Blinded, Controlled Trial

Abstract

Background

Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients.

Methods

In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45−60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck’s Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population.

Discussion

This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery.

Trial Registration

Chinese Clinical Trial Registry (ChiCTR2200064348).

Keywords:

• esketamine
• perimenopausal women
• depressive symptoms
• breast cancer
• modified radical mastectomy

Abbreviations

ASA, American Society of Anesthesiologists; BDI, Beck’s Depression Inventory; PACU, Post-anesthesia care unit; PONV, Postoperative nausea and vomiting; QoR-15, Quality of Recovery-15; SAS, Self-rating Anxiety Scale; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials; SSRS, Social Support Rating Scale; VAS, Visual Analogue Scale.

Data Sharing Statement

Data available at chictr.org.cn (ChiCTR2200064348). All data relevant to the study is included in this manuscript. The prospective listing of the study on the Chinese Clinical Trial Registry can be found at https://www.chictr.org.cn/showproj.html?proj=179003.

Ethics Approval and Consent to Participate

The trial protocol was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (Approval No. 2022-204) on August 4, 2022. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, identifier: ChiCTR2200064348) on October 3, 2022. This study will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all patients.

Acknowledgments

We would like to thank all patients, therapists, supervisors and research assistants who will participate in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

This work is supported by the Suzhou Medical Health Science and Technology Innovation Project (SKY2022136 to KP), Jiangsu Medical Association Anesthesia Research Project (SYH-32021-0036 (2021031) to KP), College Students’ Extracurricular Academic Research Project of Soochow University (KY2023101A to JHH), National Natural Science Foundation of China (82072130 to FHJ), Key Medical Research Projects in Jiangsu Province (ZD2022021 to FHJ), and Suzhou Clinical Medical Center for Anesthesiology (Szlcyxzxj202102 to FHJ). The funders have no role in study design, management, data collection, analysis, data interpretation, writing of the report, or the decision to submit the report for publication.