What is the evidence for perioperative administration of duloxetine in patients undergoing total knee or hip arthroplasty for postoperative pain management and narcotic consumption reduction?
AMSTAR Rating
Summary
Patient Population:
9 randomized controlled trials (RCTs) met eligibility criteria, encompassing a total pooled sample size of n = 806 patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) for advanced, symptomatic osteoarthritis. Patient age averages across the included primary trials ranged from 51.5 to 69.0 years old, with severe baseline arthritic degeneration.
Intervention:
Perioperative oral administration of duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI). Dosage protocols specified either 30 mg or 60 mg once daily. Delivery durations varied from starting 2 to 10 weeks preoperatively up to starting on the day of surgery and continuing through postoperative day 14 to week 8.
Comparison:
Inactive placebo control capsules administered according to identical oral dosing schedules within identical multi-center multimodal analgesia frameworks (including regional anesthesia, nerve blocks, or regular post-treatment oral NSAIDs).
Outcome:
Quantitative meta-analysis demonstrated that duloxetine significantly decreased visual analog scale pain scores at rest (rVAS) and upon ambulation (aVAS) across multiple post-surgical windows (24 hours, 2 weeks, and ≥ 3 months) compared to placebo.
Additionally, duloxetine significantly reduced postoperative cumulative opioid oral morphine equivalents (MMEs) at 24 hours (Standardized Mean Difference [SMD] = -0.71; 95% CI, -1.19 to -0.24; p = 0.003), 3 days (SMD = -1.10; 95% CI, -1.70 to -0.50; p = 0.0003), and 1 week postoperatively (SMD = -1.18; 95% CI, -1.99 to -0.38; p = 0.004).
Safety profiles indicated that duloxetine patients experienced a significantly lower rate of nausea (Odds Ratio [OR] = 0.62; 95% CI, 0.41 to 0.94; p = 0.02) but a significantly higher rate of central nervous system side effects, including drowsiness and somnolence (OR = 1.87; 95% CI, 1.13 to 3.07; p = 0.01).
Guideline Recommendations
| Source | Recommendation |
|---|---|
| AAOS, 2022 | Adjunctive treatment for peri-operative pain |
Outcomes Assessed
- Benefit
- Harm
- Inconclusive
Pain control v. control (Rest and Ambulation)
24 hours
2 weeks
> 3 months
Reduction of post-operative morphine equivalents (MME's)
24 hours
3 days
1 week
Safety/Side Effects
Drowsiness
Somnolence
Headache
Relevant Clinical Info
YaDeau JT, Liu SS, Fields KG, et al. Duloxetine and duloxetine-related adverse effects after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. Bone Joint J. 2022;104-B(6S):S147-154.
YaDeau et al. (2022) was a multi-center parallel-group RCT included in this meta-analysis, evaluating a total sample size of 160 patients undergoing total knee arthroplasty. Participants were randomized to receive either 60 mg daily oral duloxetine or an identical placebo control capsule starting on the morning of surgery and continuing until postoperative day 14. The trial demonstrated that while duloxetine provided valuable sub-acute pain control and significantly restricted long-term narcotic dependency at the 3-month mark, clinicians must proactively anticipate the therapy’s neuro-modulatory side effects, as the duloxetine group displayed significantly increased rates of postoperative drowsiness (18 vs. 11 cases) and headaches compared to controls.
Participant Information
The sample size was 806
There were 9 studies used.
