Duloxetine for Postoperative Pain After Knee Surgery

Overseen By Denis Nam, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Rush University Medical Center

Must not be taking: SSRIs, SNRIs, Serotonergic drugs

Disqualifiers: Psychiatric disorders, Heavy alcohol, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether duloxetine, a medication, can reduce pain and the need for opioids after knee replacement surgery. The study compares two groups: one receiving duloxetine and another receiving a placebo (a pill with no active medication). It aims to determine if duloxetine manages pain better than current treatments alone. Ideal candidates for this trial are those planning knee replacement surgery due to osteoarthritis and who have not previously used certain mental health medications. As a Phase 4 trial, duloxetine is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

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 is the safety track record for duloxetine?

Research has shown that duloxetine is generally safe and can help with pain after surgeries like knee replacements. Many studies have found that participants tolerated duloxetine well, experiencing few serious side effects. Most side effects were mild, such as nausea or fatigue. Since the FDA has already approved duloxetine for other uses, its safety profile is well-established. Therefore, using duloxetine for post-surgery pain is considered safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about duloxetine for managing postoperative pain after knee surgery because it offers a unique approach compared to standard treatments like opioids and NSAIDs. Duloxetine is typically used as an antidepressant and for nerve pain, but it has a different mechanism: it works by increasing levels of serotonin and norepinephrine in the brain, which can help modulate pain perception. This could potentially reduce reliance on traditional painkillers, which often come with significant side effects and addiction risks. Additionally, duloxetine is taken orally and can be started before surgery, potentially providing more comprehensive and sustained pain relief.

What evidence suggests that duloxetine might be an effective treatment for postoperative pain after knee surgery?

Studies have shown that duloxetine, which participants in this trial may receive, can effectively reduce pain and lower the need for strong painkillers after knee surgery. Research indicates that patients taking duloxetine feel less pain and can begin rehab exercises sooner. A review of several studies supports that duloxetine helps manage pain and reduces the need for opioids. However, some studies found no major differences between duloxetine and opioids in terms of pain control and function over a year. Overall, duloxetine has proven effective for managing pain after knee replacements. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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

Willingness to undergo randomization and return for all scheduled visits

I am having a knee replacement due to arthritis.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Duloxetine
• Placebos

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

In a clinical trial with 68 patients undergoing high tibial osteotomy, those who received perioperative duloxetine (40 mg/day) experienced significantly lower knee pain scores on postoperative days 1, 7, and 14 compared to the control group.

Patients in the duloxetine group also required significantly fewer non-steroidal anti-inflammatory drugs for pain management and showed improved function in sports at 3 months post-surgery, indicating that duloxetine enhances both pain relief and recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative duloxetine administration reduces pain after high tibial osteotomy and non-steroidal anti-inflammatory administration: A prospective, controlled study. Otsuki, S., Okamoto, Y., Ikeda, K., et al.[2022]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9957748/

Duloxetine for Postoperative Pain Control Following Knee or ... Duloxetine appears to decrease postoperative pain and opioid consumption following total joint arthroplasty.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9997837/

Effect of duloxetine on pain relief after total knee arthroplasty This is consistent with our results. To sum up, duloxetine can effectively relieve postoperative pain and accelerate rehabilitation exercises.

3. researchgate.net researchgate.net/publication/368502903_Duloxetine_for_Postoperative_Pain_Control_Following_Knee_or_Hip_Replacement_A_Systematic_Review_and_Meta-Analysis

Duloxetine for Postoperative Pain Control Following Knee ... This meta-analysis aims to evaluate the efficacy of duloxetine in reducing pain and postoperative opioid use following lower extremity total ...

4. bmcmusculoskeletdisord.biomedcentral.com bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-021-04168-x

Efficacy and safety of duloxetine for postoperative pain after ... The primary outcome is the intensity of residual pain at six months after TKA, including the visual analogue scale, 11-point numeric rating ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0253641

Efficacy of duloxetine compared with opioid for postoperative ... Duloxetine and opioid did not show any difference in pain control, function, and side effects for up to one year after TKA.

6. go.drugbank.com go.drugbank.com/drugs/DB00476

Duloxetine: Uses, Interactions, Mechanism of Action Improve decision support & research outcomes with our structured adverse effects data. See a data sample. Toxicity. Overdose ... Postoperative pain / Total Knee ...