Real-World Psilocybin Therapy for Treatment-Resistant Depression: a Retrospective Observational Study

Abstract Psilocybin has demonstrated promising antidepressant effects in depression and treatment-resistant depression (TRD) in controlled clinical trials. However, its effectiveness and safety in real-world therapeutic settings remain largely unknown. Although psilocybin is not yet approved as an antidepressant treatment, Switzerland’s unique legal framework allows its limited medical use for TRD. We conducted a retrospective analysis of medical records from 19 TRD patients treated with psilocybin (20-35mg) across one to four dosing sessions at the Psychiatric University Hospital Zurich. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Beck Depression Inventory II (BDI). Changes from baseline to interim and post-treatment were analyzed, including response, remission, and the reliable change index. MADRS scores significantly decreased from baseline ( M = 30.78) to post-treatment ( M = 19.89), with a large effect size (Hedges’ g = 1.37, p