A 2023 meta-analysis evaluated the efficacy of duloxetine in reducing pain and postoperative opioid use following lower extremity total joint arthroplasty (TJA). Among eight identified randomized controlled trials, six studies investigated duloxetine for total knee arthroplasty (TKA), one study investigated duloxetine for total hip arthroplasty (THA), and one study investigated both TKA and THA. Perioperative dosing regimens of duloxetine varied among trials, with a common regimen of 60 mg given 30 minutes to two hours preoperatively followed by 60 mg postoperatively for 14 days. While the quantitative analysis found no significant difference in opioid consumption at 24 hours between duloxetine- and placebo-recipients, use of duloxetine was associated with less opioid use at 48 (weighted mean difference [WMD] -11.98; 95% confidence interval [CI] -21.32 to -2.65; p= 0.012) and 72 (WMD -10.73; 95% CI -21.37 to -0.09; p= 0.048) hours. [1]
Patients receiving duloxetine experienced significantly lower visual analog scale (VAS) scores at rest at postoperative day 3 (POD 3; WMD -0.52; 95% CI: -0.83 to -0.22; p= 0.001), POD 7 (WMD -0.80; 95% CI -1.38 to -0.22; p= 0.007), and postoperative week 6 (WMD -2.01; 95% CI -2.41 to -1.61; p<0.001). For VAS with movement, significantly reduced pain was reported by duloxetine-treated patients at POD 1 (WMD -0.72; 95% CI -1.31 to -0.13; p= 0.016), POD 3 (WMD -0.56; 95% CI -0.99 to -0.12; p= 0.012), POD 7 (WMD -0.96; 95% CI -1.41 to -0.50; p<0.001), POD 14 (WMD -1.02; 95% CI -1.72 to -0.33; p= 0.004), postoperative week 6 (WMD -1.41; 95% CI -1.79 to -1.02; p<0.001), and postoperative month 3 (WMD -0.80; 95% CI -1.56 to -0.04; p= 0.038). While the preliminary data demonstrate duloxetine as a viable adjunctive agent in the setting of TJA procedures, variations in dosing regimens and inconsistent placebo use among evaluated trials may ameliorate the robustness of the overall conclusion. [1]
Another recent meta-analysis published in 2023 evaluated the efficacy and safety of duloxetine for postoperative recovery specifically after TKA. A total of 11 studies (N= 1,019) of patients undergoing TKA for primary knee osteoarthritis were included for analysis. Duloxetine had no statistically significant reduction in pain at rest compared with control at 24 hours (standard mean difference [SMD] -0.43; 95% CI -1.06 to 0.2; p= 0.18). However, compared with control, duloxetine showed a statistically significant reduction in pain at rest at 3 days (SMD -0.35; 95% CI -0.65 to -0.05; p= 0.02), 1 week (SMD -0.56; 95% CI -1.02 to -0.1; p= 0.02), 2 weeks (SMD -0.73; 95% CI -1.31 to -0.14; p= 0.02), and 6 weeks (SMD -0.78; 95% CI -1.36 to -0.21; p= 0.02). No significant differences were reported in pain at rest between duloxetine and control at 12 weeks, 6 months, and 12 months. [2]
For pain with movement, duloxetine again had no significant improvement compared with control at 24 hours (SMD -0.46; 95% CI -0.96 to 0.03; p= 0.07). However, duloxetine showed significant improvements compared to control for pain with movement at 5 days (SMD -0.65; 95% CI -1.21 to -0.09; p= 0.02), 1 week (SMD -0.74; 95% CI -1.12 to -0.36; p= 0.0001), 2 weeks (SMD -0.83; 95% CI -1.30 to -0.36; p= 0.0006), 4 weeks (SMD -0.98; 95% CI -1.33 to -0.62; p <0.00001), 6 weeks (SMD -0.99; 95% CI -1.84 to -0.13; p= 0.02), and 8 weeks (SMD -1.23; 95% CI -1.72 to -0.73; p<0.00001). Again, no significant differences for pain with movement were reported at 12 weeks, 6 months, and 12 months, indicating its long-term effects on pain may be limited. [2]
Duloxetine was found to significantly improve physical function compared with control at 1 week (SMD -1.79; 95% CI -2.56 to -1.01; p<0.00001), 2 weeks (SMD -1.44; 95% CI -1.89 to -0.99; p<0.00001), 4 weeks (SMD -1.54; 95% CI -2.62 to -0.46; p= 0.005), and 8 weeks (SMD -1.13; 95% CI -1.77 to -0.49; p= 0.0005). In terms of analgesic consumption, no significant differences between duloxetine and control were reported for consumption of patient-controlled analgesia with intravenous morphine or fentanyl. Cumulative opioid consumption at 24 hours, however, was significantly lower with duloxetine compared to the control group (MD -7.26; 95% CI -14.34 to -0.18; p= 0.04). At 7 days, no significant difference in cumulative opioid consumption occurred. [2]
Duloxetine showed significant improvements in range of motion of the knee at 6 weeks (MD 3.96; 95% CI 1.11 to 6.81; p= 0.006) compared to control, but not at 1 week or 12 weeks. Duloxetine also resulted in a lower score on the depression scale than in the control groups (MD -2.74; 95% CI -3.91 to -1.56; p<0.00001) and a better score on the SF-36 for mental health (MD 11.47; 95% CI 7.73 to 15.21; p <0.00001). Overall, no significant publication bias was noted within the analysis, and sensitivity analyses found the effect on pain on movement at 1 week to be similar when removing one study that was a significant source for heterogeneity. The rates of adverse events between duloxetine and control groups were similar within studies. [2]
A 2021 meta-analysis aimed to determine if duloxetine 60 mg given perioperatively is safe and effective at reducing postoperative opioid consumption and reported pain following elective orthopedic surgery. Five randomized controlled trials were included in the analysis (N= 314) for postoperative opioid consumption (24-hour period) and three studies for the 48-hour postoperative period. Duloxetine use was associated with statistically significant lower total opioid use at 24 hours (mean difference [MD] -31.9 MME [morphine milligram equivalents]; 95% confidence interval [CI] -54.22 to -9.6; p= 0.005) and overall (MD -31.68 MME; 95% CI -46.62 to -16.74; p<0.0001). In terms of adverse events, duloxetine use resulted in an increase in insomnia and decreased incidence of dizziness and somnolence in one study; other adverse events were similar between duloxetine and placebo groups in the included studies. The most notable adverse events reported were nausea and vomiting. The authors concluded that these results suggest adding preoperative administration of 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 events. These results are limited by significant heterogeneity among the included studies, small sample sizes, and that various orthopedic surgeries were included; these factors limit the overall validity and generalizability of the meta-analysis. [3]