Duloxetine for the reduction of opioid use in elective orthopedic surgery: a systematic review and meta-analysis


Background Duloxetine is currently approved for chronic pain management; however, despite some evidence, its utility in acute, postoperative pain remains unclear Aim of the review This systematic review and meta-analysis is to determine if duloxetine 60 mg given perioperatively, is safe and effective at reducing postoperative opioid consumption and reported pain following elective orthopedic surgery. Method CINAHL, Medline, Cochrane Central Registry for Clinical Trials, Google Scholar, and Clinicaltrials.gov were searched using a predetermined search strategy from inception to January 15, 2019. Covidence.org was used to screen, select, and extract data by two independent reviewers. Individual study bias was assessed using the Cochrane Risk of Bias tool. Opioid consumption data were converted to oral morphine milligram equivalents (MME) and exported to RevMan where meta-analysis was conducted using a DerSimonian and Laird random effects model. Results Six randomized-controlled trials were included in the literature review of postoperative pain and adverse effects. Five studies were utilized for the meta-analysis of postoperative opioid consumption; totaling 314 patients. Postoperative pain analysis showed variable statistical significance with overall lower pain scores with duloxetine. Adverse effects included an increase in insomnia with duloxetine but lower rates of nausea and vomiting. Meta-analysis revealed statistically significant [mean difference (95% CI)] lower total opioid use with duloxetine postoperatively at 24 h [− 31.9 MME (− 54.22 to − 9.6), p = 0.005], 48 h [− 30.90 MME (− 59.66 to − 2.15), p = 0.04] and overall [− 31.68 MME (− 46.62 to − 16.74), p < 0.0001]. Conclusion These results suggest that adding perioperative administration duloxetine 60 mg to a multimodal analgesia regimen within the orthopedic surgery setting significantly lowers total postoperative opioid consumption and reduces pain without significant adverse effects.

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We thank Jaques YaDeau (Department of Anesthesiology, Hospital for Special Surgeries, New York, USA) for providing us the complete dataset of their study published in Anesthesiology [17].


This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Branton, M.W., Hopkins, T.J. & Nemec, E.C. Duloxetine for the reduction of opioid use in elective orthopedic surgery: a systematic review and meta-analysis. Int J Clin Pharm (2021). https://doi.org/10.1007/s11096-020-01216-9

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  • Duloxetine
  • Multimodal analgesia
  • Opioid
  • Orthopedic surgery
  • Postoperative pain
  • Spinet
  • Total knee arthroplasty