The finding:
This is a prospective, randomized, double-blinded, placebo-controlled clinical trial conducted in India, investigating the efficacy of a low dose of duloxetine as a pain management tool for patients undergoing bilateral total knee arthroplasty. Researchers found that duloxetine started two days pre-operatively effectively reduced pain (at rest and in motion) in the acute postoperative period, improved patient satisfaction, and decreased the need for additional non-steroidal anti-inflammatory drugs compared to a placebo. While duloxetine provided significantly better pain relief in the first two weeks, there was no significant difference in pain levels between the duloxetine and placebo groups at the four-week and three-month follow-ups. Notably, for both groups, at four weeks and three months, visual analogue scale(VAS) scores were lower than they were pre-operatively. Duloxetine was generally safe and well-tolerated at the 20mg dose, with the most common side effect being nighttime drowsiness.

Strength and weaknesses:
The methodology is strong, and focusing on such a narrow patient population with limited co-administered medications removes potential confounders. There is a limited generalizability due to the exclusion of all patients with positive depression or anxiety screens, but this also helps support that duloxetine can be helpful for pain separately from its benefit to mood or anxiety. They excluded patients with “central sensitivity,” but the exact screening process is vague, and this is a major weakness. It is hard to know if the results would have been different if the post-op pain control included opioid medications. Overall, this paper is an important addition to understanding of how duloxetine can be beneficial for pain outside of the chronic pain/neuropathic pain realm.

Relevance:
With the safety outcomes suggesting that adding low dose duloxetine is a low-risk intervention, and the VAS measurement timepoints demonstrating that the effects on pain happen within one week of duloxetine administration, this randomized control trial may help us have a lower threshold to recommend low-dose duloxetine, regardless of psychiatric history, if pain is contributing to mood or participation in medical care post-operatively. A major caveat is that this study showed the effects of duloxetine without co-administration other psychotropic medications, and we should continue to review for kidney dysfunction, cumulative risk of complication from platelet dysfunction, CYP2D6 mediated drug-drug interactions, along with other factors that could increase the risk of adverse effects of duloxetine use.