Perioperative esketamine exposure and postoperative depression and anxiety in elderly patients undergoing joint replacement surgery: a retrospective cohort study
Mao Li, Wen Wen, Xiang Wen
BMC Anesthesiology August 26, 2026 DOI: 10.1186/s12871-026-04199-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cohort study Randomized Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Elderly patients aged 65–80 years undergoing unilateral hip or knee joint replacement surgery |
| Intervention | Esketamine |
| Duration | Assessments at baseline (T0), postoperative day 3 (T3), and postoperative day 7 (T7) |
| Measures | Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Visual Analogue Scale (VAS), serum IL-6, TNF-α, and BDNF levels |
| Topics | Anxiety Depression Esketamine |
| Key findings | Combined perioperative esketamine exposure was associated with lower postoperative depression and anxiety scores at days 3 and 7, alongside transiently lower IL-6 and TNF-α and higher BDNF, with no difference in pain scores or adverse events. The authors state that prospective multicenter randomized controlled trials are needed to confirm these findings. |
Abstract
Postoperative depression and anxiety are common in elderly patients undergoing joint replacement surgery and may affect recovery. Esketamine has rapid antidepressant effects, but evidence for combined perioperative use remains limited, particularly in elderly patients undergoing joint replacement surgery. This study evaluated the association between combined perioperative esketamine exposure and postoperative psychological outcomes and related biomarkers. This single-center retrospective cohort study included 60 elderly patients (65–80 years) undergoing unilateral hip or knee joint replacement surgery. Patients were categorized into an esketamine exposure group ( n = 30) and a non-esketamine group ( n = 30). The primary outcomes were postoperative depressive and anxiety symptom severity assessed using the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) at baseline (T0), postoperative day 3 (T3), and postoperative day 7 (T7). Pain was evaluated using the Visual Analogue Scale (VAS). Serum IL-6, TNF-α, and BDNF levels at T0, T3, and T7 were obtained from existing research records. Mixed-effects and multivariable regression analyses were performed. Baseline characteristics were comparable between groups ( P > 0.05). The esketamine exposure group showed significantly lower HAMD and HAMA scores at T3 and T7 ( P < 0.05). IL-6 and TNF-α levels were lower at T3 ( P < 0.05), while BDNF levels were higher at T3 and T7 ( P < 0.01). No significant differences were observed in VAS scores or adverse events ( P > 0.05). Multivariable analysis showed that combined perioperative esketamine exposure was independently associated with lower postoperative psychological scores. This study suggests that combined perioperative esketamine exposure was associated with lower postoperative depression and anxiety scores, accompanied by transient reductions in inflammatory cytokines and increased serum BDNF levels, without an increased incidence of adverse events. Prospective multicenter randomized controlled studies are warranted to confirm these findings. Not applicable.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Perioperative esketamine exposure was associated with lower postoperative depression and anxiety scores at days 3 and 7, with no difference in pain scores or adverse events.
Synthesized
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Combined perioperative esketamine exposure was associated with lower postoperative anxiety scores at days 3 and 7, alongside transiently lower IL-6 and TNF-alpha and higher BDNF.
Synthesized
Comparable studies
Other observational and cohort studies on esketamine for anxiety, most cited first.