240 patients undergoing total knee arthroplasty were randomized to receive either standard of care (Group A; n=60), cognitive behavioral therapy (CBT) alone (Group B; n=60), zolpidem tartrate alone (Group C; n=60), or CBT + zolpidem tartrate (Group D; n=60). Outcomes of interest included the Pittsburgh Sleep Quality Index (PSQI), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), Interleukin-6 (IL-6), pain on a Visual Analog Scale (VAS), knee circumference, Generalized Anxiety Disorder-7 (GAD-7), American Knee Society (AKS) score, 12-item Short Form Health Survey (SF-36), and perioperative adverse reactions. Outcomes were assessed up to five postoperative days. CBT + zolpidem tartrate, CBT alone, and zolpidem alone improved sleep quality-related issues, postoperative pain, functional recovery, and quality of life. The trial demonstrated that a combined approach of psycho-behavioral and zolpidem tartrate significantly improved sleep quality, reduced pain and inflammation, enhanced functional recovery, and increased patient satisfaction.