Effect of Duloxetine on Opioid Use After Total Knee Arthroplasty

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.