Influence of low-dose esketamine on postoperative depressive symptoms in patients with breast cancer (EASE): study protocol for a randomised controlled trial

INTRODUCTION: Depressive symptoms have surfaced as the principal mental health concern among patients with breast cancer, with surgical interventions potentially exacerbating these symptoms and adversely influencing clinical outcomes. This study protocol is designed to investigate the efficacy of low-dose esketamine administered perioperatively on depressive symptoms in patients with breast cancer. It also aims to illuminate the potential neurobiological underpinnings of this effect. METHODS AND ANALYSIS: This research represents a single-centre, prospective, randomised, double-blind, placebo-controlled study. The trial anticipates enrolling 108 female patients exhibiting mild-to-severe depressive symptoms who are slated for radical mastectomy. Through stratified randomisation, eligible patients will be systematically assigned to either the esketamine group (0.25 mg/kg) or placebo group (0.9% saline) in a 1:1 ratio. The primary outcome is the response rate at the third postoperative day. Secondary outcomes encompass the remission rate, depression-related scores, depression severity and safety-related endpoints. Tertiary (exploratory) outcomes involve alterations in brain-derived neurotrophic factor and resting-state functional brain connectivity. ETHICS AND DISSEMINATION: The Clinical Trial Ethics Committee at The First Affiliated Hospital of Anhui Medical University has conferred ethical approvals for this trial (approval number: PJ2023-05-25). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300071062).