Effect of subanesthetic dose esketamine on anxiety and depression in patients with breast cancer after surgery: a randomized controlled, double-blind study.

[BACKGROUND] In recent years, evidence has suggested that subanesthetic doses of esketamine may have beneficial effects on perioperative anxiety and depression. Concurrently, various factors contribute to a high incidence of perioperative depression and anxiety in the breast cancer patient population. This study aimed to explore the impact of preoperative induction and intraoperative maintenance of subanesthetic doses of esketamine on postoperative anxiety and depressive symptoms in patients undergoing breast cancer surgery.

[METHODS] A total of 120 patients with pathologically confirmed malignant breast cancer who were hospitalized and scheduled for elective surgery were randomly divided into an experimental group (ES group) or a control group (P group), with 60 patients in each group. The ES group received esketamine at a dose of 0.2 mg/kg at anesthesia induction, which was maintained with an infusion of 0.1 mg/kg/h until the end of surgery. The P group received an equivalent volume of 0.9% sodium chloride solution during the corresponding periods. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores at postoperative day 30 (POD30), analyzed using analysis of covariance (ANCOVA) with adjustment for baseline scores. Additionally, Anxiety Self-Rating Scale (SAS) scores were recorded at preoperative day 1 (baseline), postoperative day 7 (POD7), and POD30; postoperative adverse reactions within the first 24 h were documented; and pain was assessed using the Numerical Rating Scale (NRS) scores at rest at baseline and on POD1.

[RESULTS] The primary endpoint analysis revealed that at POD30, the ES group achieved a significantly greater reduction in PHQ-9 scores compared to the P group, with an adjusted mean difference of 0.96 points (95% CI 0.42–1.51,  < 0.01). Mixed-effects modeling demonstrated significant group-by-time interactions for both SAS and PHQ-9 scores, indicating superior symptom improvement in the ES group at all postoperative timepoints (SAS: POD7 β = 5.83, 95% CI 4.13–7.53; POD30 β = 7.15, 95% CI 5.45–8.85; PHQ-9: POD7 β = 1.25, 95% CI 0.45–2.05; POD30 β = 1.05, 95% CI 0.25–1.85; all  < 0.01). The ES group also exhibited significantly lower NRS pain scores at rest on postoperative day 1 ( < 0.05). Importantly, the incidence of postoperative adverse reactions within the first 24 h, including nausea, vomiting, drowsiness, and psychiatric symptoms, did not differ significantly between groups (all  > 0.05). Subgroup analyses showed consistent treatment effects across age, surgery type, comorbidity, and surgical history strata, with no significant interactive effects detected ( > 0.05 for all interactions).

[CONCLUSION] Preoperative induction and intraoperative administration of a subanesthetic dose of esketamine reduced PHQ-9 and SAS scores at postoperative day 7 and postoperative day 30, decreased postoperative pain scores, and did not increase the incidence of postoperative adverse reactions.

[TRIAL REGISTRATION] Registration number: Chinese Clinical Trial Registry ChiCTR2400087464. Date of registration: 29/07/2024.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12888-026-07837-0.