Use of serotonergic antidepressants and perioperative complications in patients undergoing lower limb arthroplasty: Systematic review and meta-analysis of comparative studies

Dimitrios Grammatikopoulos; Eustathios Kenanidis; Georgios Foukarakis; Christothea-Alexandra Tsiridis; Michael Potoupnis; Eleftherios Tsiridis

doi:10.1016/j.jor.2025.07.009

Use of serotonergic antidepressants and perioperative complications in patients undergoing lower limb arthroplasty: Systematic review and meta-analysis of comparative studies

J Orthop. 2025 Jul 18:67:318-325. doi: 10.1016/j.jor.2025.07.009. eCollection 2025 Sep.

Authors

Dimitrios Grammatikopoulos¹, Eustathios Kenanidis¹, Georgios Foukarakis¹, Christothea-Alexandra Tsiridis², Michael Potoupnis¹, Eleftherios Tsiridis¹

Affiliations

¹ Academic Orthopaedic Department, Aristotle University Medical School, General Hospital Papageorgiou, Ring Road Efkarpia, Thessaloniki, 56403, Greece.
² City St George's, University of London (Tooting), United Kingdom.

Abstract

Background: Serotonin Reuptake Inhibitors (SRIs) are commonly utilised antidepressants among populations in Western countries; however, their use has been linked to adverse effects and postoperative complications. This systematic review assessed the risk of both early and late perioperative complications in SRIs users undergoing elective total hip arthroplasty (THA) and knee arthroplasty (TKA) compared to non-users.

Methods: This study adhered to the 2020 PRISMA guidelines. A comprehensive search of PubMed, Science Direct/Scopus, and the Cochrane Database of Systematic Reviews was conducted from inception until January 2025. Comparative studies examining SRI users and non-users undergoing elective THA or TKA that addressed at least one postoperative outcome (blood loss, postoperative haemoglobin reduction, transfusion rate, length of stay, readmission and revision rate) were included. The Newcastle-Ottawa Scale was employed to evaluate the quality of the included studies. A meta-analysis was performed to assess the risk of transfusion, utilising a random-effects model.

Results: Ten comparative cohort studies, including two prospective and eight retrospective studies, were included in this analysis, involving 2,098,833 patients who underwent either elective THA or TKA. Among these patients, 418,527 were using SRIs during the perioperative period, with a mean age of 65.2 years. Our meta-analysis revealed an odds ratio of 1.78 (95 % CI, 1.11, 2.83; p = 0.02) concerning the blood transfusion rate in patients utilising SRIs, although it was characterised by considerable heterogeneity (I² = 97 %). The findings regarding length of stay, readmission rate, and revision rate were inconclusive.

Conclusion: The use of SRIs in patients undergoing elective THA and TKA may be linked to a slightly increased risk of bleeding and need for blood transfusion. However, considering the potential benefits of these medications for this patient group, it remains uncertain whether discontinuing them during the perioperative period is advisable. More high-quality studies are required to establish an etiological relationship.

Keywords: Bleeding risk; Readmission rate; Revision rate; Serotonergic antidepressant; Total hip arthroplasty; Total knee arthroplasty.

Publication types

Review