Effect of Duloxetine on the Perioperative Anxiety Status and Stress Response Following Total Hip Arthroplasty: A Randomized Controlled Trial

ABSTRACT Objective The impact of psychological factors on surgical stress response has garnered extensive attention. However, perioperative intervention strategies are still lacking for the total hip arthroplasty (THA) population without psychiatric comorbidities. This study aimed to assess the efficacy of duloxetine in perioperative anxiety status and stress response in these patients. Methods This was a double‐blind randomized controlled trial conducted between September 2021 and August 2024. Eligible patients aged over 18 years scheduled for unilateral primary total hip arthroplasty were recruited, with exclusion of patients with diagnosed mental diseases, endocrine disorders, previous psychiatric medication use, or severe hepatorenal dysfunction. A computer‐generated random sequence was used to assign 100 patients to either the duloxetine group or the placebo group. The patients received 60 mg of duloxetine or the placebo daily starting 2 days before the surgery to postoperative day two. The primary outcome was the anxiety status assessed using the Hamilton anxiety scale (HAMA). The self‐rating anxiety scale (SAS), stress response‐related inflammatory levels and neuroendocrine levels, visual analog scale (VAS), patient satisfaction, quality of recovery‐15 (QoR‐15) score, Harris hip score (HHS), University of California Los Angeles (UCLA) activity score, and adverse effects were also compared. Continuous outcomes with multiple time points were analyzed using linear mixed models, while single time point outcomes used t ‐test or Mann–Whitney U test. Preoperative to POD1 differences were assessed with paired t ‐test or Wilcoxon test. Categorical variables and response rate were analyzed using chi‐square or Fisher's exact test. Correlation analysis examined anxiety and stress biomarker relationships. Statistical significance was set at p < 0.05. Results The duloxetine group had significantly lower HAMA and SAS scores than the placebo group on POD2 (both p < 0.05). The VAS score during walking was significantly lower in the duloxetine group ( p < 0.05). Patients in the duloxetine group exhibited higher QoR‐15, HHS, and UCLA scores and better satisfaction (all p < 0.05). The erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte ratio (NLR), tumor necrosis factor alpha (TNF‐α), adrenocorticotropic hormone (ACTH), plasma cortisol (PTC), and blood glucose (BG) were significantly lower in the duloxetine group (all p < 0.05). The ESR and HAMA, ACTH and SAS, and PTC and SAS were respectively correlated (all p < 0.05). Conclusion The perioperative administration of duloxetine alleviated anxiety, reduced postoperative walking pain, improved the quality of functional recovery and satisfaction, and may reduce the stress response in patients undergoing THA. Trial Registration: Clinical Trial Register: ChiCTR2100051099.