CARES (Comprehensive Analgesic, Recovery, and Education Support) for Surgery Trial

This is a Type 1 hybrid effectiveness-implementation, three-arm, parallel randomized controlled trial (RCT) evaluating a behavioral-pharmacologic intervention for postoperative opioid management in patients with preoperative long-term opioid use (LTOU). A total of 375 participants will be enrolled across four academic medical centers: * Stanford University Medical Center, * Harvard University- Brigham and Women's Hospital, * Wake Forest University- Atrium Health Wake Forest Baptist Medical Center, and * University of Kansas Medical Center. Eligible participants will be randomized in equal allocation to one of three study conditions: * Motivational Interviewing-Guided Opioid Taper combined with tizanidine (MI-Opioid Taper + Tizanidine), * MI-Opioid Taper with placebo, or * Enhanced Usual Care (EUC). Participants will be followed for 12 months following surgery, with structured assessments of opioid use, pain outcomes, and related behavioral and clinical measures. The primary endpoint is time to return to baseline opioid use. Secondary endpoints include time to opioid cessation, time to opioid dispensing cessation, time to pain cessation, and incidence of postoperative opioid misuse. Additional exploratory analyses will examine behavioral and clinical mediators of treatment effects, including motivation for change, change talk, and pain reduction. Effect modification analyses will assess whether baseline participant characteristics are associated with differential treatment engagement and outcomes. Implementation outcomes will be evaluated using a mixed-methods approach guided by the RE-AIM framework, focusing on barriers and facilitators to future dissemination and scalability of the MI-Opioid Taper intervention. This project addresses a critical gap in postoperative care for patients with long-term opioid use in need of precision postoperative pain care to minimize opioid-related harms.