Skip to content

Esketamine-sufentanil PCA reduces postoperative depression state in elderly colorectal cancer patients: a randomized controlled trial.

Rong Ding, Daojie Wang, Guoxin Wang, Yamei Lin, Dongchen Wu, Min Zhang, Yufei Ren, Wenyue Kang, Guanwen Lin

Scientific Reports April 21, 2026 DOI: 10.1038/s41598-026-49287-4 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 99
Population Elderly (≥ 65 years) colorectal cancer resection patients
Interventions Sufentanil + esketamine 1 mg/kg Sufentanil + esketamine 2 mg/kg
Dose 1 mg/kg, 2 mg/kg
Topics Esketamine Depression
Keywords Colorectal cancer Elderly Patient-controlled analgesia Postoperative depression state
Key findings Low-dose esketamine (1 mg/kg) adjunct to sufentanil PCA significantly reduces postoperative depression and anxiety state in elderly colorectal cancer patients without enhancing analgesia or increasing adverse events.

Abstract

Elderly colorectal cancer (CRC) patients face high risks of postoperative depression state, inadequately addressed by opioid-based analgesia. Esketamine, an NMDA receptor antagonist with rapid antidepressant effects, offers potential benefits but lacks evidence in this population. This double-blind RCT enrolled 99 elderly (≥ 65 years) CRC resection patients, randomized to three postoperative PCA groups: C: Sufentanil (2 µg/kg) + saline placebo, ES1: Sufentanil + esketamine 1 mg/kg, ES2: Sufentanil + esketamine 2 mg/kg. Primary outcomes were anxiety/depression (HAMA/HAMD scores) at 24 h postoperatively. Secondary outcomes included VAS pain scores, patient satisfaction, and adverse events. Depression/Anxiety: Both esketamine groups showed significantly lower HAMD/HAMA scores vs. control at 24 h and 72 h (e.g., 24 h HAMD: ES1 6.16 ± 2.16, ES2 7.10 ± 2.55 vs. C 9.87 ± 3.67; p < 0.001), with no dose-dependent difference (p > 0.05 ES1 vs. ES2). Pain Control: No intergroup differences in resting/activity VAS scores or rescue analgesia demands (p > 0.05). Satisfaction: Higher satisfaction rates in ES1 (77.4%) and ES2 (90.0%) vs. C (50.0%) (p = 0.002). Safety: Comparable adverse events across groups (p > 0.05). Low-dose esketamine (1 mg/kg) adjunct to sufentanil PCA significantly reduces postoperative depression and anxiety state in elderly CRC patients without enhancing analgesia or increasing adverse events. Its profound psychological benefits and high patient satisfaction support its integration into enhanced recovery protocols for this vulnerable cohort. Registry: Chinese Clinical Trial Registry(chictr.org.cn), TRN: ChiCTR2300070763, Registration date: 23 April 2023.

Comparable studies

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

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

Explore topics

By condition and practice