One hundred fifty-one patients undergoing total knee arthroplasty were randomized to receive 30 mg of duloxetine daily (n=82) or placebo (n=69) from one week preoperatively to six weeks postoperatively. The primary outcome was daily opioid consumption measured as morphine milliequivalents (MME) in the first two weeks after surgery. Secondary outcomes included sleep quality and duration in the same period, as well as KOOS JR and VAS pain scores at six weeks. Outcomes were assessed daily for two weeks postoperatively and at the six-week follow-up. Overall, the study found no significant differences between the groups in MME requirements, sleep quality or duration, or KOOS JR and VAS scores. However, in patients with central sensitization, duloxetine significantly improved sleep duration (p=0.03) and self-reported restfulness (p=0.005) in the first postoperative week. These findings suggest duloxetine may have targeted benefits for specific patient populations, such as those with central sensitization.