Introduction: Total Knee Arthroplasty (TKA) is amongst the most common surgical procedures performed around the world. PaIents undergoing TKA surgeries experience post-operaIve pain that can be challenging to address. To achieve optimal pain management with opioid stewardship, mulImodal pain medication regimens are utilized. Venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI) medication is typically used for the treatment of mood disorders, but also has clinical use for treatment of neuropathic pain, with growing evidence for use in surgical seRngs. In this clinical trial, we seek to test the use of venlafaxine as an element of TKA post-operative pain management.

Hypothesis: Our null hypothesis is that there is no significant difference in pain severity, functionality scores, and opioid consumption between the two arms of the study: patients receiving venlafaxine vs. placebo. Our alternative hypothesis is that the patients receiving venlafaxine will have significant reductions in pain severity and opioid consumption, and significant increases functionality scores compared to those receiving placebo.

Aims: To compare pain severity, funcIonality, and ongoing opioid medicaIon consumption at 24 hours, seven days, and three months post-operaIvely for patients receiving venlafaxine vs. placebo aXer undergoing total knee arthroplasty.

Methods: This is a randomized control trial with quadruple blinding (parIcipant, care provider, investigator, outcomes assessor) started in May 2021 at UCSF Medical center enrolling approximately 100 patients undergoing TKA. PaIents in the experimental arm receive Venlafaxine extended release 37.5 mg per day on the day of surgery and seven days post-operatively. PaIents in the control arm receive placebo for the same Ime frame. Patients otherwise receive pain medications including opioids at their provider’s discretion. PaIents have their intra-procedure and post-operaIve inpaIent pain medication administraIon recorded from the electronic health record, and self-report outpaIent opioid medication use alongside completion of the Brief Pain Inventory at 24 hours, seven days, and three months post-operaIvely.

Results: In March 2023, the Imeline for study enrollment was expanded with 70 patients enrolled to date. As the trial data is incomplete and with blinding, there are no preliminary results to report of patients that have completed the study to date.

Discussion: This randomized control trial is a novel investigation into the use of venlafaxine for postoperative pain management for patients undergoing TKA. While the results and subsequent interpretation are not available to date, the enrollment process has been enlightening on paIent motivators for such research (negative experiences or associaIons with opioid medications, desire to contribute to well-being of future paIents) as well as apprehension (negative associaIons with “anI-depressants”, polypharmacy).