Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

Study Overview
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Brief Summary
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Post-discharge pain after total knee arthroplasty remains problematic; many patients have excessive pain at the 2 week time point (and often thereafter). Reduction in opioid use has become a national goal, due to the 'epidemic' in opioid misuse. In addition to enrolling non-opioid users, we will enroll up to 15 chronic opioid users.

Official Title
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Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty: A Double-blinded Randomized Control Trial

Conditions
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Joint Disease, Pain, Acute, Pain, Chronic

Intervention / Treatment
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* Drug: Cymbalta
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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: Current Use of duloxetine or other SNRIs, SSRIs, MAOIs, Tricyclic antidepressants, triptans (sumatriptan, rizatriptan, naratriptan, eletriptan, almotriptan, frovatriptan), lithium, buspirone, St. John's Wort Hepatic insufficiency o Hepatoxicity is reported as a side effect of duloxetine. Median time to detection of transaminase elevation was about two months (package insert 5.2 Renal insufficiency (ESRD, HD, estimated creatinine clearance < 50 ml/min) Severe CRI may impair duloxetine clearance CLcr=[(140-age (years)] x weight (kg)x0.85 (for female patients)/[72xserum creatinine (mg/dL)] 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) Patients with major prior ipsilateral open knee surgery. Chronic opioid use (taking opioids for longer than 3 months) However, patients using chronic opioids may enroll in a parallel pilot study entitled 'effect of duloxetine on opioid use after total knee athroplasty among patients exposed to opioids- a pilot study'. The chronic opioid users will be allowed to continue their customary analgesics. The pilot study is otherwise identical to the main study. This study will enroll up to 15 chronic opioid users. After that, all chronic opioid users are excluded.

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 (Cymbalta)<br>Epidural analgesia after knee arthroplasty is not as prevalent at HSS as formerly, in large part due to the rise of local infiltration analgesia. Studies using epidural analgesia may also lack generalizability given the infrequent use of epidural analgesia at other institutions. For these reasons, we plan to use adductor canal nerve blockade + local infiltration analgesia for management of immediate postoperative pain. Patients will receive spinal anesthesia as the primary anesthetic. It is particularly important to study duloxetine (Cymbalta) in the context of local infiltration analgesia, as patients receiving local infiltration analgesia receive increased doses of opioids, compared to patients receiving epidural analgesia. | Drug: Cymbalta<br>* Duloxetine (Cymbalta) is a serotonin and norepinephrine dual reuptake inhibitor (SNRI) that is an effective treatment for painful diabetic neuropathy. It is approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain<br>|
| Placebo Comparator: Placebo<br>Placebo to compare pain scores and opioid use againts Duloxetine | Other: Placebo<br>* Placebo to compare outcomes against Duloxetine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Use | Opioid use (measured in cumulative morphine equivalents) | Post-operative day 14 | 
| Pain Scores | Numerical Rating Score pain with movement. Minimum value of 0, maximum value of 10. Higher scores mean more pain and worse outcome. | Post-operative day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Phenotype | 2011 Survey Criteria for Fibromyalgia. Minimum value of 0, and maximum value of 12. A higher score means a worse outcome. | Day of surgery |