Does Duloxetine Reduce Sub-Acute Pain After Knee Arthroplasty?

Study Overview
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Brief Summary
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We are investigating the impact of duloxetine (Cymbalta), a serotonin and norepinephrine reuptake inhibitor, on pain after total knee arthroplasty (TKA). Specifically, the investigators will determine whether duloxetine, 60 mg daily for 2 weeks, reduces pain scores 2 weeks after TKA.

Official Title
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Does Duloxetine Reduce Sub-Acute Pain After Knee Arthroplasty?

Conditions
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Total Knee Arthroplasty

Intervention / Treatment
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* Drug: Placebo
* Drug: Duloxetine 60mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with osteoarthritis scheduled for primary tricompartmental total knee arthroplasty with a participating surgeon Age 25 to 75 years Planned use of regional anesthesia Ability to follow study protocol English speaking (primary outcome obtained via telephone call and secondary outcomes include questionnaires validated in English only) Patients planning on being discharged home or to a rehabilitation center that has agreed to participate Exclusion Criteria: Concurrent use of duloxetine or other SNRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort Hepatic insufficiency Renal insufficiency Patients younger than 25 years old and older than 75 Patients intending to receive general anesthesia Allergy or intolerance to one of the study medications Patients with an ASA of IV Chronic gabapentin/pregabalin use (regular use for longer than 3 months) Chronic opioid use (taking opioids for longer than 3 months) Patients with major prior ipsilateral open knee surgery

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duloxetine<br>Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken preoperatively. Starting on postoperative day (POD) 1, patients will take one capsule once a day until end of POD14. | Drug: Duloxetine 60mg<br>* Patients will receive 60mg of duloxetine per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.<br>* Other names: Cymbalta;|
| Placebo Comparator: Control<br>Patients will receive 0mg of duloxetine | Drug: Placebo<br>* Patients will receive placebo drug with no active ingredients per dose. 1 capsule will be taken pre-operatively. One capsule once a day until end of POD14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NRS Pain With Ambulation at 2 Weeks | When considering the pain in the knee in which you are having/had surgery, on a scale of 0-10, with 0 being no pain and 10 being pain as bad as you can imagine, how would you describe your level of pain in the last 24 hours during ambulation? | 2 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Daily Opioid Use (mg Oral Morphine Equivalents) | Total daily opioid use (including PO, PCEA, IV, subcutaneous, IV push) in mg oral morphine equivalents on POD 1. | POD 1 | 
| Nausea Severity | Nausea severity measured using Likert scale ranging from 0 (none) to 10 (severe). | POD 1 |