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.

Summary

In a multicenter double-blind RCT (n=130), intraoperative low-dose esketamine significantly increased response and remission rates on POD 1–3 and improved HADS-A and PHQ-9 scores, without increasing neuropsychiatric adverse events within 30 days. Findings support esketamine as a rapid-acting perioperative intervention for depressive/anxiety symptoms in patients needing repeated wound surgeries.

Key Findings

• Esketamine increased MADRS response on POD1–3 (e.g., 53.8% vs 26.2% on POD1; p=0.001) and remission (e.g., 33.8% vs 10.8% on POD1; p=0.002).
• Improved HADS-A and PHQ-9 scores by POD3 versus placebo.
• No increase in neuropsychiatric adverse events within 30 days postoperatively (assessed by YMRS, CADSS, BPRS).

Clinical Implications

Consider intraoperative low-dose esketamine as an adjunct to enhance early postoperative mental health recovery in selected surgical patients, with monitoring protocols for standard ketamine-related effects.

Limitations

• Short follow-up (30 days) and specific surgical population (repeated debridement) may limit generalizability
• Dose range (0.2–0.3 mg/kg) and optimal perioperative timing require further refinement

Future Directions

Longer-term, diverse-surgery RCTs to assess durability, functional and quality-of-life outcomes; dose-finding and comparative effectiveness versus other rapid-acting agents.