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.

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. 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- sberg 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. 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. 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.