Effect of postoperative esketamine on depression after pancreatoduodenectomy: a randomized controlled trial.
Bowen Zhang, Zhun Wang, Kaili Yu, Qian Pan, Shan Guan, Mengxue Zhang, Ruoshuang Jia, Yilin Wang, Qingxiang Meng, Ying Ma, Dongliang Mu, Yiqing Yin
Perioperative medicine (London, England) June 12, 2026 DOI: 10.1186/s13741-026-00711-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 80 |
| Population | Patients scheduled for pancreaticoduodenectomy |
| Interventions | Esketamine Sufentanil |
| Dose | 1.5 mg/kg esketamine and 2 µg/kg sufentanil |
| Duration | Follow-up to one year |
| Measures | Hamilton Depression Scale (HAMD-17) |
| Topics | Esketamine Depression |
| Keywords | Analgesia Pancreaticoduodenectomy Postoperative depression |
| Key findings | Esketamine added to patient-controlled analgesia did not significantly reduce the incidence of depression on postoperative day three (47.1% vs 42.9%), but was associated with greater improvement in HAMD-17 scores from baseline to day five, fewer PCIA button presses, lower opioid consumption, and reduced IL-6 and TNF-α concentrations. The authors suggest it may reduce analgesic needs, alleviate peripheral inflammation, and potentially improve postoperative depressive symptoms. |
Abstract
Pancreaticoduodenectomy (PD) can lead to major trauma in terms of patients' mental health, including severe postoperative depression. This study aimed to investigate the effects of supplementing patient-controlled analgesia with low-dose esketamine on postoperative depression among patients undergoing PD. Eighty patients who were scheduled for PD were randomly assigned to either the control or esketamine groups. The control group received 2 µg/kg of sufentanil for patient-controlled analgesia (PCIA), whereas the esketamine group received a combination of 1.5 mg/kg esketamine and 2 µg/kg sufentanil. The primary outcome was the incidence of depression on the third postoperative day. The secondary outcomes included the Hamilton Depression Scale (HAMD-17) scores on the first, second, third, and fifth postoperative days; the severity of postoperative pain; the analgesic dosage; the incidence of postoperative adverse effects; the concentrations of plasma 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); and the one-year survival rate. The incidence of depression on the third postoperative day did not differ significantly between the two groups (47.1% vs. 42.9%, P = 0.726). However, the change in the HAMD-17 score between baseline and the fifth postoperative day was significantly lower in the esketamine group (P = 0.029). The number of PCIA button presses was significantly lower in the esketamine group than in the control group (9.32 ± 6.48 vs. 6.54 ± 4.39, P = 0.040), and opioid usage was also significantly lower in the esketamine group (114.9 ± 23.32 vs. 100.9 ± 25.72, P = 0.021). Furthermore, esketamine decreased the plasma concentration of IL-6 on the first postoperative day (P < 0.05) and that of TNF-α on the fifth postoperative day (P < 0.05). The postoperative administration of esketamine may reduce the need for analgesics among patients undergoing PD, alleviate peripheral inflammation, and potentially improve postoperative depressive symptoms. This trial was registered at http://www.chictr.org.cn (ChiCTR2200066303, Principal investigator: Yinqing Yin, Date of registration: 2022-11-30).