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Esketamine for Postoperative Anxiety After Major Abdominal Tumor Surgery: A Randomized Clinical Trial

Xiaoying Cui, Wutao Chen, Jinyu Wang, Xiaobing Xiang, Meijuan Zhu, Ze Chai, Siqun Xiao, Shunv Cai, Pingbo Xu, Wen Zhang

Drug Design Development and Therapy September 1, 2026 DOI: 10.2147/dddt.s632479 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 180
Population Patients with preoperative anxiety scheduled for major abdominal tumor surgery
Interventions Esketamine placebo
Duration Follow-up to postoperative day 30
Measures Hamilton Anxiety Rating Scale (HAMA)
Topics Anxiety Esketamine
Key findings Esketamine did not reduce postoperative anxiety in patients with preoperative anxiety undergoing major abdominal tumor surgery: response rates on postoperative day 3 were 39.5% with esketamine versus 42.5% with placebo, and anxiety scores were similar at days 3 and 30. Esketamine was associated with lower depressive symptom scores at day 30.

Abstract

Purpose: Postoperative anxiety is common in surgical patients and may impair recovery, especially in the patients with preoperative anxiety. However, effective strategies for treating postoperative anxiety remain limited. We hypothesized that esketamine could reduce postoperative anxiety in patients with preoperative anxiety undergoing major abdominal tumor surgery. Patients and

Methods: 180 patients with preoperative anxiety scheduled for major abdominal surgery were randomly assigned to either esketamine or placebo. The primary outcome was the response rate on postoperative day 3 (POD3), defined as a ≥ 50% reduction from baseline Hamilton Anxiety Rating Scale (HAMA) score. Secondary outcomes included HAMA score on POD3 and POD30, depression and quality of recovery on POD3 and POD30, sleep quality on POD1-3 and POD30.

Results: 86 patients in the esketamine group and 87 patients in the placebo group were analyzed. On POD3, the positive response rate was 39.5% in the esketamine group and 42.5% in the placebo group (risk ratio, 0.93; 95% CI, 0.65 to 1.33; P = 0.81). The secondary outcomes showed that HAMA scores were similar between groups at POD3 (median [IQR], 6 [3– 10] vs 7 [4– 11]; adjusted mean difference, 0; 95% CI, − 2 to 1; P = 0.59) and at POD30 (5 [3– 8] vs 7 [4– 11]; adjusted mean difference, − 1; 95% CI, − 3 to 1; P = 0.28). Patients in the esketamine group also demonstrated lower scores for depressive symptoms on POD30 (median [IQR], 5 [2– 8] vs 6 [3– 10]; adjusted mean difference, − 2; 95% CI, − 3 to − 1; P = 0.001).

Conclusion: Esketamine did not reduce anxiety in patients with preoperative anxiety undergoing major abdominal tumor surgery on POD3 and POD30. Keywords: abdominal tumor surgery, anxiety, depression, esketamine, sleep quality

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

  • Esketamine did not reduce postoperative anxiety compared with placebo, with similar response rates and anxiety scores at days 3 and 30, though depressive symptom scores were lower at day 30.

    Synthesized

  • Esketamine did not reduce postoperative anxiety compared to placebo: response rates on postoperative day 3 were 39.5% with esketamine versus 42.5% with placebo, and anxiety scores were similar at days 3 and 30.

    Synthesized

Comparable studies

Other randomized controlled trials on esketamine for anxiety, most cited first.

Study Year Design Participants
Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Patients with treatment resistant depression 2020 Randomized controlled trial
Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response Patients with treatment-resistant depression 2021 Pooled post hoc analysis of two phase 3, double-blind, active-controlled studies
Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray Patients with treatment-resistant depression 2023 Post hoc analysis of two pooled phase 3 double-blind placebo- and active-controlled trials n = 518
Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant Patients aged 18-64 years with treatment-resistant depression 2023 Phase 3, randomized, double-blind, short-term flexibly dosed study n = 223
The effect of esketamine on postoperative anxiety and depression in patients with thyroid cancer: A randomized, double-blind, placebo-controlled, parallel-group trial. Female patients with thyroid cancer scheduled for surgery under general anesthesia 2025 Randomized controlled trial n = 80

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