Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty
Condition: Joint Disease; Pain, Acute; Pain, Chronic
MeSH terms: Joint Diseases; Acute Pain; Chronic Pain
Intervention: Cymbalta; Placebo
Intervention description: 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; Placebo to compare outcomes against Duloxetine
Intervention MeSH terms: Duloxetine Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 160.0
Sex: All
Minimum age: 25 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.