Effect of esketamine on postoperative depression and anxiety in patients undergoing cardiac valve surgery: a randomised, placebo-controlled, double-blinded clinical trial.
Zhuo-Ning Zhang, Xin-Yu Hao, Chen Cai, Li Sun, Zi-Yi Zhang, Miao Wang, Yi-Shuang Wu, Ying Wang, Jiang-Bei Cao, Yan-Hong Liu, Jing-Sheng Lou, Qiang Fu, Sheng-Li Jiang, Ru-Quan Han, Wei-Dong Mi, Li Tong
Pharmacological Research November 22, 2025 DOI: 10.1016/j.phrs.2025.108047 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 142 |
| Population | Patients undergoing cardiac valve surgery |
| Intervention | Esketamine |
| Dose | 0.3 mg/kg |
| Duration | Postoperative day 7 |
| Topics | Anxiety Depression Esketamine |
| Keywords | Cardiac valve surgery Esketamine esketamine Postoperative depression Postoperative anxiety Mental recovery Major surgery Neurobiological mechanisms bdnf Increased bdnf levels Reduced inflammation |
| Citations | 5 |
| Registration | NCT06608030 |
| Key findings | A single dose of esketamine at anesthesia induction significantly reduces postoperative depression and anxiety at day 7 compared to placebo. |
Abstract
This randomized, double-blind, parallel-group trial evaluated the efficacy of a single intravenous dose of esketamine (0.3mg/kg) administered at anesthesia induction in reducing postoperative depression and anxiety among patients undergoing cardiac valve surgery. A total of 142 patients from three centers were randomly assigned to receive esketamine or saline. The primary outcomes were the prevalence of depression and anxiety at postoperative day (POD) 7, assessed by the Hospital Anxiety and Depression Scale (HADS). Key secondary outcomes included delirium incidence, pain and insomnia scores, and quality of recovery. Results showed that the esketamine group had significantly lower rates of depression (7.0% vs. 31.0%; P<0.001) and anxiety (11.3% vs. 35.2%; P<0.001) at POD 7, along with reduced delirium incidence (9.8% vs. 22.5%; P=0.040). Improvements were also observed in pain, sleep, and recovery quality. Mechanistic analyses revealed that esketamine reduced inflammatory markers (IL-6, CRP) and neuronal injury marker (S100β), while increasing brain-derived neurotrophic factor (BDNF). No significant differences in adverse events were observed. In conclusion, a single low dose of esketamine during induction effectively alleviates early postoperative depression and anxiety, possibly through modulating neuroinflammation and promoting neurotrophic signaling. (Clinicaltrials.gov, ID Number: NCT06608030).