Perioperative duloxetine helps after joint replacement, modestly

A meta-analysis of 13 randomised trials (1,176 patients) tested perioperative duloxetine as part of multimodal analgesia for total hip and knee replacement.

Duloxetine significantly reduced pain at rest (mean difference -5.09 mm on a 100 mm scale at 24 hours) and on walking, with benefit persisting to two weeks. It spared opioids at 48 hours (-22.74 morphine milligram equivalents) and 72 hours (-10.58), though the 48-hour estimate had extreme heterogeneity (I² = 100%) and a very wide interval, so should be read with caution. It reduced nausea and vomiting (risk ratio 0.73) but increased drowsiness (risk ratio 1.88). Several findings lost significance when a single high-risk trial was removed.

The honest reading is that duloxetine offers a real but sub-threshold analgesic effect and useful opioid-sparing in the first three days, at the cost of sedation worth warning patients about. It is a reasonable component of a multimodal plan in selected patients, not a large independent effect.

• Small but significant reductions in rest and ambulatory pain to 2 weeks
• Opioid-sparing at 48–72 h, but the 48-h estimate is very imprecise (I² = 100%)
• Less nausea/vomiting (RR 0.73); more drowsiness (RR 1.88) — counsel patients
• Fragile: several results lost significance on leave-one-out analysis

The statistics, in plain English

A pain reduction of about 5 mm on a 100 mm scale is statistically significant but below the ~10 mm usually considered clinically meaningful — hence 'sub-threshold'. An I² of 100% for the 48-hour opioid estimate means the trials disagreed almost completely, so that particular number is unreliable even though it reached significance.

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