Real-World Psilocybin Therapy for Treatment-Resistant Depression: a Retrospective Observational Study
Johannes Jungwirth, Samuel Westenhöfer, Helena Aicher, Barbora Provaznikova, Golo Kronenberg, Erich Seifritz, Susanne Prinz, Sebastian Olbrich
December 10, 2025 preprint DOI: 10.21203/rs.3.rs-8079137/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cohort study |
|---|---|
| Sample size | 19 |
| Population | Patients with treatment-resistant depression treated at the Psychiatric University Hospital Zurich |
| Intervention | Psilocybin |
| Dose | 20–35mg |
| Topics | Depression Psilocybin |
| Keywords | Observational study Dosing Depression economics Antidepressant Adverse effect Rating scale Retrospective cohort study Interim Clinical trial Randomized controlled trial Beck depression inventory Depressive symptoms Major depressive episode Medical record Severity of illness Imipramine |
| Key findings | Psilocybin treatment was associated with significant and clinically meaningful reductions in depressive symptoms in patients with treatment-resistant depression, with response and remission rates below those reported in previous trials. |
Abstract
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 < .001). BDI scores also decreased significantly ( M = 32.33 to M = 23.28), with a large effect ( r = .80, p = .003). Response and remission rates were 33.3% and 22.2% (MADRS), and 27.8% and 27.8% (BDI). No additive effect of multiple dosing was found. No serious adverse events occurred. We observed a significant and clinically meaningful reduction in depressive symptoms after psilocybin treatment, with response and remission rates below those reported in previous trials. Although observational and limited by its sample size, this study provides some of the first real-world evidence on psilocybin. Larger, prospective trials are needed to confirm our findings and identify predictors to increase treatment effectiveness.