Postoperative acute pain management with duloxetine as compared to placebo: A systematic review with meta-analysis of randomized clinical trials

BackgroundDuloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral duloxetine, when given perioperatively, is any better than a placebo in managing postoperative pain. Effects of duloxetine on postoperative pain scores, time to first rescue analgesia, postoperative rescue analgesia consumption, side effects attributable to duloxetine, and patient satisfaction profile were assessed. MethodMEDLINE, Web of Science, EMBASE, Scholar Google, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched with keywords including "Duloxetine" AND "postoperative pain", "Duloxetine" AND "acute pain" and with "Duloxetine" till October 2022. This meta-analysis included randomized clinical trials in which perioperative duloxetine 60 mg per oral was administered not more than 7 days before surgery and for at least 24 after surgery but not more than 14 days after surgery. All RCTs in which the comparator is placebo and outcomes related to analgesic efficacy like pain scores, opioid consumption, and side effects of duloxetine until 48 h postoperatively were included. Data were extracted from the studies and a risk of bias summary was formed using the Cochrane Collaboration tool. Effect sizes were given as standardized mean differences for continuous outcomes and risk ratios (RR) by the Mantel-Haenszel test for the categorical outcome. Confirmation of publication bias was done by Egger's regression test (p < 0.05). If publication bias or heterogeneity was detected, the trim-and-fill method was used to calculate the adjusted effect size. Sensitivity analysis was done by leaving one out method after excluding the study with a high risk of bias. Subgroup analysis was done based on the type of surgery and gender. The study was prospectively registered in the PROSPERO under the registration number CRD42019139559. Findings29 studies with 2043 patients met the inclusion criteria and were reviewed for this meta-analysis. Postoperative pain scores at 24 h [Std. Mean Difference (95% CI); -0.69 (-1.07, -0.32)] and at 48 h [-1.13 (-1.68, -0.58)] are significantly less with duloxetine (p-value < 0.05). Time to first rescue analgesia was significantly more in patients where duloxetine was administered [1.27 (1.10, 1.45); p-value > 0.05]. Opioid consumption up to 24 h [-1.82 (-2.46, -1.18)] and 48 h [-2.48 (-3.46, -1.50)] was significantly less (p-value < 0.05) in patients who received duloxetine. Complications and recovery profiles were similar in patients receiving either duloxetine or a placebo. InterpretationBased on GRADE findings, we conclude that there is low to moderate evidence to advocate the use of duloxetine for managing postoperative pain. Further trials are needed to replicate or refute these results based on robust methodology.