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HSS Researchers Find Duloxetine May Reduce Opioid Use and Improve Pain Management After Total Knee Replacement

In a study conducted by researchers at Hospital for Special Surgery (HSS), cumulative opioid use was reduced by 30% in a patient group that received duloxetine after total knee arthroplasty (TKA) compared with patients who received placebo. 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 2021 Spring American Society of Regional Anesthesia and Pain Medicine (ASRA) Annual Meeting.1

Studies have demonstrated that many patients report joint pain two weeks after TKA.2 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 one to two days after TKA. However, patients often have significant and troubling pain during the first two 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 HSS. “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 or placebo once daily for 14 days after surgery and answered questions on postoperative days one, two, seven, 14, six weeks, and 90 days. 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.

HSS is committed to patient safety and being a leader in effective pain management. Its Controlled Substances Task Force continues to make strides in patient education and safe prescribing.

In addition to this study, HSS 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.


1. Danya A. DeMeo BS, Ejiro Gbaje MPH, Jacques T. YaDeau MD PhD, Kethy M. Jules-Elysee MD, Yi Lin MD PhD, Enrique A. Goytizolo MD, David Kim MD, Richard L Kahn MD, Stephen C. Haskins MD, David J. Mayman MD, Douglas E. Padgett MD, Thomas P. Sculco MD, Chad M. Brummett MD, Geoffrey Westrich MD. “Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty. A Double-Blinded Randomized Control Trial.” Presented at: 46th Annual Regional Anesthesiology and Acute Pain Medicine Meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA), May 13-15, 2021; Orlando, FL.

2. 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.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.