Duloxetine May Reduce Opioid Use, Improve Pain Management After TKA

    Cumulative opioid use was reduced by 30% in patients who received the antidepressant medication duloxetine after total knee arthroplasty (TKA) compared with patients who received placebo, according to a study from researchers at Hospital for Special Surgery.

    Patients who received duloxetine also reported higher pain management satisfaction and less pain interference with mood, walking, normal sleep, and work activities.

    These findings were presented at the American Society of Regional Anesthesia and Pain Medicine’s recent 46th Annual Regional Anesthesiology and Acute Pain Medicine Meeting.

    Studies have demonstrated that many patients report joint pain 2 weeks after TKA. [1] Given the status of the ongoing opioid epidemic, it is critical to study safe and effective alternative pain treatments.

    “Previous research has shown us how to keep most patients relatively comfortable for the first 1 or 2 days after TKA. However, patients often have significant and troubling pain during the first 2 weeks, once the nerve blocks wear off. They often take large amounts of opioids,” said principal investigator Jacques Ya Deau, MD, PhD, an anesthesiologist at Hospital for Special Surgery.

    “It is important to reduce postoperative opioid use without increasing pain or worsening the patient experience.”

    Finding alternative strategies for pain relief after TKA is imperative, as improved postoperative pain management is linked to improved patient satisfaction, faster rehabilitation, and reduced complications.

    Dr. Ya Deau and colleagues enrolled 160 patients undergoing TKA into the study and randomized them into a duloxetine or placebo group. Patients took 60 mg of oral duloxetine, a serotonin and norepinephrine dual reuptake inhibitor, or placebo once daily for 14 days after surgery and answered questions on POD1, POD2, POD7, and POD14, and at six weeks and 90 days after surgery. Postoperative pain management also included acetaminophen, ketorolac, meloxicam, and oxycodone as needed.

    The researchers collected data on numerical rating scale (NRS) scores for pain management, opioid consumption, patient satisfaction, and questions based on the Brief Pain Inventory.

    Duloxetine was found to be better than placebo for reducing opioid use and was of equal efficacy to placebo for reducing pain. Duloxetine was also better than placebo for patient satisfaction and for the effect of pain on mood, walking, working, and sleeping.

    “Duloxetine, given on the day of surgery and once daily for 14 days afterwards, reduces opioid use by about 30%. Patients receiving duloxetine are more satisfied with their pain management, and pain interferes less with their activities and mood,” Dr. Ya Deau said.

    In addition to this study, Hospital for Special Surgery is ramping up further research on opioids with the help of a $3 million grant from the Starr Foundation.

    “Future research could examine optimum duration of therapy and determine whether duloxetine is also useful for other orthopedic procedures. We also need to try to understand barriers to adoption of duloxetine as a postoperative analgesic,” Dr. Ya Deau concluded.


    DeMeo DA, Gbaje E, Ya Deau JT, Jules-Elysee KM, Lin Y, Goytizolo EA, Kim D, Kahn RL, Haskin SC, Mayman DJ, Padgett DE, Sculco TP, Brummett CM, Westrich G. Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty. A Double-Blinded Randomized Control Trial. Presented at the American Society of Regional Anesthesia and Pain Medicine’s 46th Annual Regional Anesthesiology and Acute Pain Medicine Meeting, May 13-15, 2021, in Orlando, Florida.


    1. Lewis GN, Rice DA, McNair PJ, Kluger M. Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis. Br J Anaesthe 2015; 114: 551-61.