Perioperative duloxetine for acute postoperative analgesia: a meta-analysis of randomized trials

Abstract

BackgroundMultimodal 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.MethodsA 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.Results574 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.ConclusionDuloxetine, 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 numberCRD42019121416

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…The relative safety profiles of the gabapentinoids in perioperative settings are therefore unlikely to differ when use is limited to short-term, low doses. Duloxetine, a serotonin- and norepinephrine-reuptake inhibitor with analgesic properties, has also been effective in perioperative multimodal regimens, representing a potential alternative to gabapentinoids [ 205 , 206 , 207 , 208 , 209 , 210 ].…”

An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens

“…For chronic pain management, tricyclic antidepressants are the most commonly used antidepressants. However, the efficacy of selective serotonin (SSRI) and serotonin-noradrenaline reuptake inhibitors (SNRI) to decrease pain and reduce the need for opioid therapy has been studied [156,157,158].…”

“…Duloxetine, a medication of the SNRI family, has been shown in controlled randomized trials to decrease pain in diabetic and non-diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, in postoperative analgesia, pain in the orofacial region, and exceptionally for acute pain [157,159]. With almost no effect upon cholinergic and histaminergic receptors, duloxetine and other SNRIs are primarily indicated for depressive and anxiety disorders, despite the increase in available evidence supporting their use as an analgesic.…”

Evaluation of Analgesic Efficacy and Opioid-sparing Effect of Duloxetine After Arthroscopic Rotator Cuff Repair

“…22 Therefore, we chose 60 mg as the standard dose in this study. Zorrilla-Vaca et al 23 included 574 patients in a metaanalysis about perioperative duloxetine for acute postoperative analgesia, which concluded that duloxetine could reduce pain scores at 4 and 48 hours postoperatively compared with placebo. However, the mean differences were both <1, which indicated no clinical significance.…”