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Background: Patients undergoing neurosurgical procedures frequently experience substantial preoperative anxiety and physiologic stress, which may adversely affect perioperative outcomes and patient well-being. Music medicine has emerged as a promising non-pharmacological intervention for reducing stress and enhancing the patient experience; however, mechanistic evidence linking music interventions to biological markers of stress and inflammation remains limited. The Music-STAR Trial (NCT06536504) was designed to evaluate the impact of simulated live and recorded music interventions on psychological and biological measures of stress and anxiety in neurosurgical patients.

Methods: Music-STAR is a prospective, three-arm randomized controlled trial conducted at MD Anderson Cancer Center. A total of 132 patients undergoing neurosurgical procedures are being randomized to receive either simulated live music via a Steinway Spirio player piano, recorded music, or standard preoperative care. Music selections adhere to a validated, reproducible framework designed to promote relaxation. Participants receive a 30-minute intervention immediately before surgery. Outcomes include validated measures of anxiety, mood, and pain (STAI-S, POMS-SF, VAPS), physiologic parameters, and serum- and plasma-level biomarkers assessed through proteomic and metabolomic analyses.

Results: Interim analysis of the first 52 participants in the music intervention arms demonstrated clinically meaningful reductions in perceived and biologic stress. Compared with baseline, patients receiving music interventions exhibited a 36% reduction in State-Trait Anxiety Inventory–State (STAI-S) scores and a 32% reduction in serum cortisol levels. Concurrently, serum oxytocin concentrations increased by 28%, suggesting enhanced neuroendocrine mechanisms associated with relaxation and emotional regulation. Proteomic and metabolomic analyses revealed significant reductions in inflammatory mediators, including hydroxyeicosatetraenoic acids (HETEs), indicating attenuation of stress-related inflammatory pathways following a single 30-minute intervention.

Conclusions: Preliminary findings from the Music-STAR Trial demonstrate measurable psychobiological effects of music medicine in neurosurgical patients. Music interventions reduced anxiety, cortisol, and inflammatory biomarkers while increasing oxytocin, supporting music medicine as a scalable, low-risk strategy for modulating stress physiology and enhancing perioperative care.