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Efficacy and safety evaluation of intravenous esketamine in alleviating perioperative depressive symptoms in Parkinson’s disease: a randomized controlled trial

Wei Tan, Yuanyuan Gao, Dan Su, Lin Ji, Shu Wang

BMC Anesthesiology April 15, 2026 DOI: 10.1186/s12871-026-03839-3 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled trial Peer reviewed
Sample size 53
Population Patients with Parkinson's disease undergoing non-intracranial surgery
Intervention Esketamine
Dose 0.25 mg/kg IV bolus at induction followed by 0.125 mg/kg/h infusion
Duration Assessed preoperatively and on postoperative days 1, 3, and 7
Measures Self-Rating Depression Scale (SDS), Visual Analogue Scale (VAS), serum 5-HT, norepinephrine (NE), IL-6, TNF-alpha
Topics Esketamine
Key findings Low-dose intraoperative intravenous esketamine reduced postoperative depressive symptoms in Parkinson's disease patients undergoing non-intracranial surgery, with lower Self-Rating Depression Scale scores at all postoperative time points through day 7, increased serotonin but not norepinephrine, and reduced IL-6, TNF-alpha, and pain scores, with comparable adverse events. The authors propose these effects may involve serotoninergic and neuroinflammatory modulation.

Abstract

Depressive symptoms frequently afflict individuals with Parkinson’s disease (PD). The current study was consequently conducted to determine the efficacy of low-dose intravenous esketamine in managing postoperative depressive symptoms, thereby exploring its potential mechanisms of action in PD patients subjected to non-intracranial surgery. In this randomized, double-blind, placebo-controlled trial, patients were allocated to receive either low-dose esketamine (0.25 mg/kg IV bolus at induction followed by 0.125 mg/kg/h infusion) or placebo. The primary outcome was the Self-Rating Depression Scale (SDS) score assessed preoperatively and on postoperative days 1, 3, and 7. Secondary outcomes included serum levels of 5-HT, norepinephrine (NE), IL-6, and TNF-α, postoperative pain (VAS), and adverse events. A total of 53 patients were enrolled, including 27 patients (mean age:72.93 ± 6.59, 14 males, mean BMI 22.87 ± 2.71) in the control group (C group), and 26 patients (mean age: 70.46 ± 7.85, 11 males, mean BMI 23.32 ± 3.40) in the esketamine group (ES group). Compared to the control group, ES group showed significantly lower SDS scores at all postoperative time points (p < 0.01), with sustained antidepressant effects through day 7. Esketamine selectively increased 5-HT (p = 0.0005) but not NE levels. It also significantly reduced proinflammatory cytokines (IL-6, p < 0.001; TNF-α, p < 0.001) and VAS scores (p < 0.001). The incidence of adverse events was comparable between groups. Low-dose intraoperative intravenous esketamine safely mitigates postsurgical depressive symptoms in PD patients following non-intracranial surgery, potentially through synergistic modulation of serotoninergic activity and neuroinflammatory responses. http://www.chictr.org.cn, ChiCTR2500098063, Registration date: 3 March 2025. Retrospectively registratered.

Comparable studies

Other randomized controlled trials on esketamine, 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

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