Psilocybin-assisted therapy for treatment-resistant depression in the US: a model-based cost-effectiveness analysis

Introduction

Major depressive disorder (MDD) is highly prevalent in the United States, affecting an estimated 21 million adults (8.3% of the adult population) and generating substantial health, social and economic costs. Around one-third of people with MDD do not respond adequately to available treatments, a condition commonly labelled treatment-resistant depression (TRD), which is associated with higher mortality and greater healthcare and societal costs. Earlier randomised trials have reported promising antidepressant effects of psilocybin-assisted therapy (PAT): for example, a 6-week trial (N = 104) found 25% sustained remission after a single dose versus 9.1% with active placebo, and a TRD-focused RCT (N = 79) reported a three-week remission rate of 29% for single-dose PAT versus 13.7% for standard third-line antidepressants. PAT delivery in trials has required substantial therapist time and supervised dosing sessions, raising questions about its resource intensity and economic value relative to existing TRD treatments. Avanceña and colleagues set out to estimate the short-term cost-effectiveness of single-dose PAT as a third-line therapy for adults with TRD in the US. Using a model-based analysis, the study compares PAT to a weighted mix of standard third-line care (pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), and esketamine) over a 12-month horizon, and it examines how determinants such as the cost of PAT and its effectiveness influence whether PAT meets commonly used US cost-effectiveness thresholds. The authors position this as the first analysis of PAT economics in a US context, intended to inform trial design, pricing and coverage decisions should PAT be approved.