Efficacy and safety of perioperative esketamine for postoperative depressive symptoms in breast cancer patients: a meta-analysis

Background: Postoperative depressive symptoms may impair recovery and quality of life in patients undergoing breast cancer surgery. Esketamine has shown potential antidepressant and analgesic effects in the perioperative setting. This meta-analysis evaluated the efficacy and safety of perioperative esketamine for postoperative depressive symptoms in patients undergoing breast cancer surgery.

Methods: PubMed, Embase, Cochrane Library, Web of Science, CNKI, and WanFang were systematically searched from database inception to 18 May 2026. Randomized controlled trials comparing perioperative esketamine with control interventions in patients undergoing breast cancer surgery were included. The primary outcome was postoperative depressive symptom score. Secondary outcomes included postoperative pain scores and adverse events. Random-effects models were used as the primary analytical approach. Risk of bias and certainty of evidence were assessed using the RoB 2 tool and the GRADE approach, respectively.

Results: Fifteen randomized controlled trials involving 1,515 patients were included. Perioperative esketamine was associated with significantly lower postoperative depressive symptom scores at postoperative day 1 (SMD = -0.78, 95% CI: -1.08 to -0.48), postoperative day 3 or 48-72 h (SMD = -1.07, 95% CI: -1.63 to -0.51), postoperative day 7 (SMD = -0.79, 95% CI: -1.10 to -0.49), and long-term follow-up (SMD = -1.16, 95% CI: -1.68 to -0.64). For postoperative pain, esketamine was associated with lower postoperative pain scores at postoperative day 1 or 24 h (MD = -0.66, 95% CI: -1.11 to -0.21) and postoperative day 3 or 48-72 h (MD = -0.66, 95% CI: -1.09 to -0.23), but not at postoperative day 7. However, substantial heterogeneity and wide prediction intervals were observed for pain outcomes. The incidences of nausea and vomiting, postoperative delirium, and dizziness did not differ significantly between the esketamine and control groups. The certainty of evidence ranged from low to very low across outcomes.

Conclusion: Perioperative esketamine may reduce postoperative depressive symptom scores and provide short-term analgesic benefits in patients undergoing breast cancer surgery. However, substantial heterogeneity, methodological limitations, and low to very low certainty of evidence warrant cautious interpretation. Further high-quality randomized trials are needed. Systematic Review

Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251173178, identifier CRD420251173178.