Effect of duloxetine on pain and opioid consumption after total knee and hip arthroplasty: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid consumption in patients after total hip or knee arthroplasty.

Aim: This systematic review and meta-analysis aimed to analyze pain control, opioid consumption, and associated adverse events of perioperative administration of duloxetine after total hip or knee arthroplasty.

Method: After being registered with PROSPERO (CRD42022323202), the databases of MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception until March 20, 2023, for randomized controlled trials (RCTs). Primary outcomes were the visual Analog Scale (VAS) pain scores at rest (rVAS) and upon ambulation (aVAS). Secondary outcomes were postoperative opioid consumption quantified as oral morphine milligram equivalents (MMEs) and adverse effects of duloxetine.

Results: Nine RCTs with 806 cases were included. Duloxetine was associated with lower VAS scores at different times after surgery (24 h, two weeks, and ≥ 3 months). Compared to placebo, perioperative daily duloxetine use significantly reduced daily opioid MMEs at 24 h (standard mean deviation [SMD] -0.71, 95% confidence interval [95% CI] -1.19 to -0.24, P = 0.003), three days (SMD -1.10, 95% CI -1.70 to -0.50, P = 0.0003), and one week (SMD -1.18, 95% CI -1.99 to -0.38, P = 0.004) after surgery. The duloxetine group had a significantly lower rate of nausea (odds ratio 0.62, 95% CI [0.41 to 0.94], P = 0.02) and a higher rate of drowsiness and somnolence (odds ratio 1.87, 95% CI [1.13 to 3.07], P = 0.01) compared to the placebo group. No significant differences were observed in the rates of other adverse events.

Conclusion: Perioperative duloxetine significantly decreased postoperative pain and opioid consumption with good safety profiles. Further high quality designed and well-controlled randomized trials are warranted.

Keywords: Duloxetine; Opioid consumption; Postoperative pain; Total hip arthroplasty; Total knee arthroplasty.