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).
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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A single 0.3 mg/kg dose of esketamine at anesthesia induction lowered rates of anxiety at postoperative day 7 (11.3% vs 35.2%) and depression compared with placebo, with reduced delirium and no difference in adverse events.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for anxiety, most cited first.
Citations in the library
Cited by 2
- Effect of intraoperative esketamine on moderate-to-severe depressive symptoms in major surgery patients: A randomized clinical trial. Pharmacological Research July 1, 2026
- Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial. Annals of medicine July 3, 2026
Cites 9
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
- Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ April 10, 2024
- Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery JAMA Network Open March 6, 2024
- Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies Molecular Psychiatry January 20, 2023
- Effect of Esketamine on Postoperative Delirium in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass: A Randomized Controlled Trial. Anesthesia & Analgesia October 1, 2024
and 4 more in the library