Duloxetine for Postoperative Pain After Knee Surgery

Overseen By Denis Nam, MD, MSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Rush University Medical Center

Must not be taking: SSRIs, SNRIs, Serotonergic drugs

Disqualifiers: Psychiatric disorders, Heavy alcohol, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if duloxetine can help reduce pain and opioid use in patients after knee replacement surgery. It focuses on patients who often have severe pain or heightened pain sensitivity. Duloxetine may work by altering brain chemicals to lessen pain signals. Duloxetine has been shown to have significant pain-relieving effects for managing chronic pain associated with conditions like fibromyalgia and diabetic peripheral neuropathic pain.

Will I have to stop taking my current medications?

The trial requires that you have not used SSRIs, SNRIs, or serotonergic drugs (except tramadol) in the past 6 months. If you are taking these medications, you would need to stop before participating.

What data supports the effectiveness of the drug duloxetine for postoperative pain after knee surgery?

Research shows that duloxetine can help reduce the need for opioids (strong painkillers) and lower pain levels after knee surgery. It has been effective in managing pain for patients with central sensitization (a condition where the nervous system is more sensitive to pain) after knee replacement surgery. ^{1 2 3 4 5}

Is duloxetine safe for humans when used for postoperative pain after knee surgery?

Duloxetine is generally safe for humans, but it may cause some side effects like insomnia, while reducing nausea and vomiting compared to a placebo. It has been studied for various conditions, showing it can help manage pain with a good safety profile. ^{3 4 5 6 7}

How does the drug duloxetine differ from other treatments for postoperative pain after knee surgery?

Duloxetine is unique because it is a serotonin and norepinephrine reuptake inhibitor (SNRI) that not only helps reduce postoperative pain but also decreases the need for opioids and enhances patient satisfaction after knee surgery. Unlike traditional painkillers, it may also lower wound temperature and is generally safe with manageable side effects like headache and nausea. ^{3 5 8 9 10}

Eligibility Criteria

This trial is for adults under 80 years old who are having a knee replacement due to osteoarthritis and can speak English. They must be willing to follow the study plan and return for check-ups. People with severe health issues, mental disorders, heavy alcohol use, opioid tolerance, or kidney problems cannot join.

Inclusion Criteria

English speaking

I am 18 years old or older.

Willingness to undergo randomization and return for all scheduled visits

Exclusion Criteria

Non-English speaking

Non-independent (i.e. requires a caretaker to make medical decisions on their behalf)

I have been taking at least 60 morphine equivalents daily for the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgery Treatment

Participants in the experimental arm receive 30 mg of duloxetine daily starting one week prior to surgery

1 week

Post-surgery Treatment

Participants continue to receive 30 mg of duloxetine daily for 6 weeks following surgery

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse medication effects and patient-reported outcomes

Up to 3 months

Treatment Details

Interventions

• Duloxetine (Serotonin-Norepinephrine Reuptake Inhibitor)
• Placebos (Other)

Trial Overview The trial tests if duloxetine reduces pain and opioid need after knee surgery compared to a placebo (a pill without medicine). It also looks at how it affects patient-reported outcomes. Participants will be randomly assigned to either receive duloxetine or a placebo.

Participant Groups

Group I: Duloxetine Experimental Treatment 1 Intervention

Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally (per os \[PO\]) daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage.

Group II: Control Placebo Group 1 Intervention

Patients randomized to the control arm will receive PO-matched placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing TKA at Rush University Medical Center.

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

In a study involving 60 patients undergoing major colonic surgeries, duloxetine did not significantly reduce postoperative morphine consumption compared to a placebo, indicating it may not be effective for this purpose.

Pain intensity at rest and during movement also showed no significant differences between the duloxetine and placebo groups in the first 48 hours after surgery, suggesting that duloxetine may not provide additional pain relief in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of a short-term perioperative duloxetine treatment on post-colectomy pain: A randomized, controlled clinical trial. Erdmann, TR., Gerber, MT., Gaspareto, PB., et al.[2022]

This randomized, placebo-controlled trial aims to evaluate the efficacy of duloxetine in reducing postoperative residual knee pain in patients with preoperative central sensitization (CS) after total knee arthroplasty (TKA), with a focus on pain intensity measured at six months post-surgery.

Patients in the duloxetine group will receive a preemptive dose before surgery and a full dose after, allowing for a comprehensive assessment of duloxetine's safety and effectiveness in managing pain compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of duloxetine for postoperative pain after total knee arthroplasty in centrally sensitized patients: study protocol for a randomized controlled trial. Wang, S., Wang, W., Shao, L., et al.[2021]

In a study involving 100 patients undergoing total knee arthroplasty, perioperative use of duloxetine significantly reduced both resting and ambulation pain scores compared to a placebo, indicating its efficacy in managing acute postoperative pain.

Patients taking duloxetine also consumed less opioids post-surgery, suggesting that it can help decrease opioid use without increasing the risk of adverse effects, making it a valuable addition to pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effect of perioperative duloxetine in patients after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial. Yuan, M., Tang, T., Ding, Z., et al.[2022]

Duloxetine 60 mg administered perioperatively significantly reduces total postoperative opioid consumption in patients undergoing elective orthopedic surgery, with a mean difference of -31.68 MME overall, indicating its efficacy in pain management.

While duloxetine is associated with increased insomnia, it also results in lower rates of nausea and vomiting, suggesting it is a safe addition to multimodal analgesia regimens without major adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for the reduction of opioid use in elective orthopedic surgery: a systematic review and meta-analysis. Branton, MW., Hopkins, TJ., Nemec, EC.[2021]

In a 13-week study involving 231 patients with knee osteoarthritis, duloxetine significantly reduced pain scores compared to placebo, showing effectiveness as early as Week 1.

Duloxetine also improved physical functioning and other secondary outcomes without a significant increase in adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. Chappell, AS., Ossanna, MJ., Liu-Seifert, H., et al.[2022]

Duloxetine significantly reduces postoperative pain scores at 24 and 48 hours compared to placebo, indicating its efficacy in managing acute postoperative pain based on a meta-analysis of 29 studies involving 2043 patients.

Patients receiving duloxetine also required less opioid rescue analgesia within the first 48 hours post-surgery, while experiencing similar side effects and recovery profiles as those on placebo, suggesting it is a safe adjunct for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative acute pain management with duloxetine as compared to placebo: A systematic review with meta-analysis of randomized clinical trials. Govil, N., Arora, P., Parag, K., et al.[2023]

Duloxetine has been shown to effectively reduce postoperative pain and morphine consumption in patients undergoing total knee arthroplasty (TKA), based on a systematic review of nine studies involving 942 participants.

The medication is generally safe, with common side effects including headache and nausea, but no serious adverse events reported, indicating it could be a viable option for managing pain after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analgesic effect and safety of duloxetine in total knee arthroplasty: A systematic review. Kouhestani, E., Minaei, R., Salimi, A., et al.[2023]

Preemptive duloxetine significantly reduced postoperative pain levels in patients with central sensitization after total knee arthroplasty, as evidenced by lower pain scores up to 6 weeks post-surgery.

Duloxetine also resulted in lower wound temperatures compared to placebo, indicating potential benefits for wound healing, although there were no differences in wound complication rates between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preemptive Duloxetine Relieves Postoperative Pain and Lowers Wound Temperature in Centrally Sensitized Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. Kim, MS., Koh, IJ., Sung, YG., et al.[2021]

Duloxetine significantly reduces postoperative pain after total knee arthroplasty, particularly at rest and during movement from 3 days to 8 weeks post-surgery, based on a meta-analysis of 11 studies involving 1019 patients.

The use of duloxetine also improves physical function and range of motion of the knee within 1 to 6 weeks, while lowering opioid consumption within the first 24 hours after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis. Yang, JM., Wang, Y., Li, JY., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effects of a short-term perioperative duloxetine treatment on post-colectomy pain: A randomized, controlled clinical trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of duloxetine for postoperative pain after total knee arthroplasty in centrally sensitized patients: study protocol for a randomized controlled trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Analgesic effect of perioperative duloxetine in patients after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Duloxetine for the reduction of opioid use in elective orthopedic surgery: a systematic review and meta-analysis. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Perioperative duloxetine administration reduces pain after high tibial osteotomy and non-steroidal anti-inflammatory administration: A prospective, controlled study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Postoperative acute pain management with duloxetine as compared to placebo: A systematic review with meta-analysis of randomized clinical trials. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The analgesic effect and safety of duloxetine in total knee arthroplasty: A systematic review. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Preemptive Duloxetine Relieves Postoperative Pain and Lowers Wound Temperature in Centrally Sensitized Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Duloxetine for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis. [2023]