Esketamine significantly reduces postoperative anxiety (SMD -1.23) and depressive symptoms (SMD -0.92) in adult patientsEsketamine reduces anxiety and depression after surgery

IntroductionThis study aims to systematically evaluate, through a systematic review and meta-analysis, the effect of esketamine on postoperative negative emotions (anxiety and depression) and cognitive function in patients undergoing general anesthesia.MethodsFollowing PRISMA guidelines, we systematically searched PubMed, Web of Science, Embase, Cochrane Library, and CNKI to identify studies up to April 2025. Included randomized controlled trials (RCTs) involved adults undergoing general anesthesia, comparing perioperative esketamine to placebo/standard care, and reporting outcomes on negative emotions or cognitive function. Risk of bias was evaluated using Cochrane RoB 2.0, and Data were synthesized using R 4.3.3 with random-effects models; heterogeneity and robustness were assessed via I2 statistics and sensitivity analyses.ResultsThirteen RCTs involving 1,312 patients were included. Esketamine significantly reduced depressive (SMD = −0.92, 95% CI: [−1.39, −0.46]) and anxiety symptoms (SMD = −1.23, 95% CI: [−1.71, −0.75]), with low certainty of evidence for both outcomes. Cognitive outcomes were heterogeneous: MMSE showed no significant effect overall (SMD = 0.22, 95% CI: [−0.87, 1.30]) but became significant after excluding an outlier (SMD = 0.65, 95% CI: [0.39, 0.90]), while MoCA results remained non-significant (SMD = 0.93, 95% CI: [−0.99, 2.84]), and the certainty of evidence for MMSE and MoCA was rated very low.ConclusionEsketamine demonstrates robust antidepressant and anxiolytic effects postoperatively, while its cognitive benefits remain unclear owing to high heterogeneity and very low evidence certainty. Although these findings support the potential application of esketamine in perioperative emotional management, the low to very low overall certainty of evidence justifies the need for further high-quality, large-scale RCTs to clarify its cognitive effects and establish optimal dosing regimens.Systematic review registrationIdentifier, CRD420251078985.