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Perioperative duloxetine for acute postoperative analgesia: a meta-analysis of randomized trials
  1. Andrés Zorrilla-Vaca1,
  2. Alexander Stone2,
  3. Andres Fabricio Caballero-Lozada1,
  4. Stephania Paredes3 and
  5. Michael Conrad Grant4
  1. 1Anesthesiology, Universidad del Valle, Cali, Colombia
  2. 2Anesthesiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Medicine, Icesi University, Cali, Colombia
  4. 4Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
  1. Correspondence to Dr Andrés Zorrilla-Vaca, Anesthesiology, Universidad del Valle, Cali 25360, Colombia; andres.zorrilla{at}


Background Multimodal analgesia is a fundamental part of modern surgery and enhanced recovery pathways. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, has been validated for the treatment of chronic neuropathic pain. The evidence for duloxetine as an adjunct for the treatment of acute postoperative pain remains controversial. We conducted a meta-analysis to determine the efficacy of duloxetine in the acute perioperative setting.

Methods A literature search was conducted in the major databases (PubMed, EMBASE and Google Scholar) for randomized controlled trials (RCTs) evaluating duloxetine compared with placebo control for acute postoperative pain. The primary outcome was postoperative pain assessed at 2, 4, 6, 24 and 48 hours time frames. Secondary outcomes included postoperative opioid administration, as well as side effects, such as postoperative nausea/vomiting (PONV), pruritus, dizziness and headache.

Results 574 patients (n=9 RCTs) were included in the analysis, divided between duloxetine (n=285 patients) and placebo (n=289 patients). Duloxetine use was associated with a significant reduction in pain scores as early as 4 (mean difference (MD) −0.9, 95% CI −1.33 to −0.47) and as late as 48 (MD −0.94, 95% CI −1.56 to −0.33) hours postoperatively compared with placebo. In addition, duloxetine was associated with a significant reduction in opioid administration at 24 (standardized MD (SMD) −2.24, 95% CI −4.28 to −0.19) and 48 (SMD −2.21, 95% CI −4.13 to −0.28) hours as well as a significant reduction in PONV (risk ratio 0.69, 95% CI 0.49 to 0.95, p=0.03) compared with placebo. There was no difference between groups in other side effects.

Conclusion Duloxetine, a non-opioid neuromodulator, may provide efficacy for the treatment of acute perioperative pain. Additional prospective studies are required to establish optimal perioperative dosing regimens, role in the setting of a comprehensive multimodal analgesic plan and impact on chronic postsurgical pain.

PROSPERO registration number CRD42019121416

  • duloxetine
  • multimodal analgesia
  • enhanced recovery pathways
  • acute pain
  • meta-analysis

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  • Contributors AZV: This author helped design the study, conduct the study, analyse the data and write the manuscript. AFC-L: This author helped conduct the literature search and analyse the data. AS: This author helped conduct the study, perform the quality assessment of the studies and write the manuscript. EP: This author helped conduct the literature search. MCG: This author helped design the study, analyze the data and write the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.