Background: Sleep disturbances are common after total joint arthroplasty (TJA) and are associated with impaired recovery, increased complications, and prolonged hospital stays. Although various pharmacological interventions have been evaluated to improve postoperative sleep quality among TJA patients, consensus on their efficacy and safety remains elusive.

Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered the protocol in the International Prospective Register of Systematic Reviews. A comprehensive search of PubMed, Embase, Scopus, and Web of Science was performed on October 5, 2024, with no language or publication date restrictions. Randomized controlled trials comparing pharmacological interventions versus routine postoperative care in TJA patients were included. Data on subjective sleep quality scores and objective measures like actigraphy and polysomnography were extracted, and the risk of bias was assessed using the National Institutes of Health randomized controlled trial tool. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. There were 24 studies involving 2,934 patients included.

Results: Meta-analysis revealed that zolpidem significantly improved sleep quality (Hedges' g = -1.510; P < 0.001) and enhanced objective sleep parameters up to three weeks postoperatively. Anticonvulsants significantly improved sleep scores (Hedges' g = -0.603; P < 0.001), although they were associated with higher adverse event rates. Melatonin and corticosteroids showed minimal or no benefit on sleep quality.

Conclusions: Although zolpidem offers significant short-term improvements in postoperative sleep quality in TJA patients, its routine use is limited by safety concerns and adverse events. Melatonin, corticosteroids, and anticonvulsants provide inconsistent benefits, underscoring the need for more rigorous, standardized, and longer-term studies to establish optimal pharmacological strategies for enhancing postoperative recovery.

Level of evidence: II.