Cost-Effectiveness of Psilocybin-Assisted Therapy Versus Standard of Care for Patients With Treatment-Resistant Depression.

Treatment-resistant depression (TRD) imposes a substantial public health and economic burden. Although psilocybin-assisted therapy (PAT) has shown clinical promise, its economic value remains uncertain. This study evaluated the cost-effectiveness of PAT compared with the standard of care for TRD. A Markov model adopting a US healthcare perspective simulated patient transitions among health states (remission, response, non-response, and relapse) every 6-week cycle. Model inputs were derived from randomized controlled trials and relevant published literature. Outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. Sensitivity analyses were conducted to assess uncertainty in key parameters, dosing regimens, retreatment strategies, and psilocybin prices. Scenario analyses extended the time horizon to 30 years to examine treatment persistence and efficacy waning. Compared with the standard of care, PAT was more effective and less costly, yielding approximately $7000 in cost savings and a gain of 0.10 QALYs per patient. These economic advantages persisted across variations in key parameters, dosing strategies, retreatment assumptions, and psilocybin prices in sensitivity analyses. Extending the horizon to 30 years in scenario analyses increased cumulative savings to $215 900 with gains of 9.87 QALYs. PAT remained cost-effective under all efficacy-waning assumptions over the 30-year horizon. This modeling analysis provides preliminary evidence that PAT may be a cost-effective option for TRD management. Consistent findings across extended time horizons suggest that its economic value is largely driven by early clinical benefits that offset downstream chronic care costs. Longitudinal real-world evidence will be essential to validate these findings and inform sustainable integration into clinical practice.