Perioperative Duloxetine May Lower Opioid Use in Total Knee or Hip Arthroplasty

Perioperative duloxetine may decrease the need for opioid consumption in patients undergoing total hip or knee replacement.

Perioperative duloxetine is associated with a moderate opioid sparing effect but increases risk for somnolence and drowsiness, according to study results published in Pain Medicine.

Many patients experience extreme pain in the 2 weeks following total knee or hip arthroplasty, and increased postoperative pain is associated with greater rehabilitation times and complication rates. As such, postoperative pain control is an important contributor to outcomes.

Several studies have reported the perioperative use of duloxetine decreased postoperative opioid use, which may have implications for postoperative pain outcomes. This systematic review and meta-analysis was designed to evaluate the effects of duloxetine in the setting of total knee or hip arthroplasty.

To that end, investigators searched publication databases through November 2022 for relevant studies. A total of 9 randomized clinical trials were included in the analysis.

The current evidence does not support the use of duloxetine for the sole purpose of reducing post-operative pain.

The study population included 806 patients, of whom 404 received duloxetine and 402 received placebo. The patients underwent total knee arthroplasty in 6 studies, total hip arthroplasty in 2 studies, and either procedure in 1 study.

On postoperative day 1, opioid consumption was similar between duloxetine and placebo recipients (mean difference [MD], -5.72; 95% CI, -16.27 to 4.82 oral morphine equivalents [OME]; I2=98%; P =.29). However, duloxetine was associated with decreased opioid consumption on days 2 (MD, -14.35; 95% CI, -26.87 to -1.83 OME; I2=97%; P =.02), 3 (MD, -13.6; 95% CI, -18.14 to -9.07 OME; I2=80%; P <.001), 7 (MD, -7.81; 95% CI, -15.18 to -0.44 OME; I2=95%; P <.001), and 14 (MD, -12.72; 95% CI, -18.21 to -7.23 OME; I2=96%; P <.001) compared with placebo.

On follow-up days 1, 3, 7, 14, and month 3, the duloxetine recipients reported significantly lower pain during activity compared with placebo (MD range, -1.09 to -0.61 points) using an 11-point pain intensity score. Similarly, on postoperative days 2, 3, 7, and 14, lower pain at rest scores were reported by duloxetine recipients compared with control (MD range, -0.86 to -0.42 points).

Duloxetine was associated with increased risk for somnolence and drowsiness compared with placebo (risk ratio [RR], 1.87; 95% CI, 1.18-2.95; I2=0%; P =.007). No group differences were observed for the risk for adverse events of nausea or vomiting, dizziness, insomnia, dry mouth, or constipation.

Study limitation include potential bias due to the heterogeneity observed in some comparisons.

The study authors concluded, “[T]he current evidence suggests that duloxetine during the perioperative period has a mild to moderate opioid sparing effect and may play a role in reducing the intensity of pain in patients undergoing knee and hip arthroplasty procedures. The current evidence does not support the use of duloxetine for the sole purpose of reducing post-operative pain.”


Azimi A, Hooshmand E, Mafi AA, Tabatabaei F-s. Effect of duloxetine on opioid consumption and pain after total knee and hip arthroplasty: a systematic review and meta-analysis of randomized clinical trials.  Pain Med. Published online April 7, 2023. doi:10.1093/pm/pnad045