The Efficacy of Sub‐Anesthesia S‐Ketamine on Postoperative Depressive Symptoms in Patients Undergoing Abdominal Tumor Resection: A Randomized Controlled Trial

Cancer patients undergoing major surgery often have perioperative depression symptoms, and are associated with worsened outcomes. We aimed to evaluate the efficacy of S-ketamine in alleviating depressive symptoms after abdominal Tumor surgery. A prospective, double-blind, placebo-controlled randomized trial was conducted, enrolling 230 patients with newly screened mild-to-severe depressive symptoms scheduled for abdominal tumor resection. Participants were randomly assigned to receive either 0.4 mg/kg of S-ketamine or normal saline. The primary outcome was the difference in treatment response rates, which defined as a 50% decrease from baseline in Patient Health Questionnaire-9 (PHQ-9) on postoperative day (POD) 1. Secondary outcomes included global quality of recovery (QoR-15) scores and adverse events. Group-based trajectory modeling was used to identify the potential trajectories of depression severity over the postoperative 7-day and the risk factors were also analyzed. On POD 1, the S-ketamine group demonstrated a slightly higher treatment response (odds ratio [OR], 1.4 [95% confidence interval (CI), 0.8 to 2.6], p = 0.017), a reduction in PHQ-9 scores (MD -1.0 [95% CI, -2.0 to 0]; p = 0.002) and higher QoR-15 scores (MD -2.2 [95% CI: -4.3 to -0.7]; p = 0.043). However, the treatment responses, PHQ-9 scores and QoR-15 scores were similar on POD 3 and 7. Adverse events were comparable between the two groups. Additionally, logistic regression did not indicate significant associations between treatment allocation. This study found the effects of sub-anesthesia S-ketamine on depressive symptoms in this patient population postoperatively were limited. The long-term efficacy needs to be explored. Chinese Clinical Trial Registry Identifier: ChiCTR 2200065298.