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

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.