Efficacy and Safety of Esketamine in Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abstract
Background: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are commonly performed procedures, but post-operative recovery is often complicated by significant pain, opioid-related side effects, and psychological distress. Esketamine has been proposed as an adjunct due to its analgesic and antidepressant properties, but its efficacy and safety remain unclear. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by searching PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) up to July 2025. Dichotomous and continuous outcomes were synthesized using risk ratios (RRs) and standardized or mean differences, each reported with 95% confidence intervals (CIs). Results: Seven RCTs involving 1,101 patients were included. Esketamine did not significantly reduce pain at rest at 12 or 24 hours. Low-certainty evidence suggested that esketamine may reduce pain during activity at 12 hours (standardized mean difference (SMD): -0.28; 95% CI: -0.45, -0.12; p < 0.001), although this effect was not sustained at 24 hours. Very low-certainty evidence suggested a possible reduction in anxiety scores at post-operative day 7, with no significant effect observed at day 1. No clear effect on depression was observed at any time point. Esketamine was associated with a higher incidence of hallucinations (RR: 4.36; 95% CI (1.48, 12.88); p = 0.01), with no significant differences in delirium, nightmares,…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,101 participants or records.
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