Psilocybin-assisted therapy in treatment-resistant depression: rapid remission, uncertain durability, and the next phase of clinical evidence
Annals of Medicine and Surgery June 18, 2026 Astrit Sabani, Adnan Khatak
Psilocybin-assisted therapy shows promise for treatment-resistant depression (TRD), defined as depression persisting after at least two adequate antidepressant trials. Early randomized trials report rapid symptom reduction and encouraging short-term remission, primarily in major depressive disorder, with limited evidence in TRD populations. However, key questions remain: whether benefits last beyond several weeks, the safety of repeated dosing, and comparisons with established treatments like esketamine, electroconvulsive therapy, and transcranial magnetic stimulation. Current evidence is limited by small samples, short follow-up, blinding challenges, and few active comparators. Implementation requires substantial therapeutic infrastructure, raising concerns about scalability, cost, and equitable access. Future research needs standardized definitions, longer outcomes, rigorous comparators, and cost-effectiveness analyses.