Esketamine hydrochloride in the management of moderate‐to‐severe depressive symptoms in patients undergoing multiple wound repair surgeries: A multi‐centre randomized, double‐blind, placebo‐controlled trial

Introduction Patients undergoing multiple wound repair surgeries often develop moderate‐to‐severe anxiety and depression. However, there is a lack of effective rapid emotional intervention strategies during the perioperative period. Methods This multi‐centre, randomized, double‐blind, placebo‐controlled trial involved 130 adult patients (65 in the esketamine group and 65 in the placebo group). Participants were randomly assigned to receive either esketamine (0.2–0.3 mg/kg) or saline intravenously during surgery. The primary outcome was the response rate (proportion of patients with ≥50% reduction in MADRS total score from baseline) on postoperative days (PODs) 1–3, evaluated using the Montgomery–Åsberg depression rating scale (MADRS). The secondary outcome was the remission rate (proportion of patients with MADRS total score ≤10) on postoperative days (PODs) 1–3; scores on the Patient Health Questionnaire‐9 (PHQ‐9), the Hospital Anxiety and Depression Scale‐Anxiety subscale (HADS‐A); and esketamine‐related neuropsychiatric adverse events assessed using the Young Mania Rating Scale (YMRS), Clinician‐Administered Dissociative States Scale (CADSS), and Brief Psychiatric Rating Scale (BPRS) within 30 days after surgery. Results The esketamine group showed a significantly higher response rate than the placebo group on POD 1–3. (POD 1: 53.8% vs. 26.2%, p = 0.001; POD 2: 60.0% vs. 40.0%, p = 0.009; POD 3: 73.8% vs. 53.8%, p = 0.018). The esketamine group also showed a higher remission rate and lower MADRS scores (POD 1: 33.8% vs. 10.8%, p = 0.002; POD 2: 40.0% vs. 23.1%, p = 0.038; POD 3: 56.9% vs. 23.1%, p < 0.001). Esketamine improved HADS‐A and PHQ‐9 scores by POD 3 without increasing neuropsychiatric adverse events within 30 days postoperatively. Conclusions The results demonstrate that the intraoperative use of low‐dose esketamine can rapidly and effectively alleviate moderate‐to‐severe anxiety and depressive symptoms in the early postoperative period (POD 1–3) among patients requiring repeated debridement surgeries without increasing neuropsychiatric or systemic adverse events within 30 days after surgery.