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.