Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - 12-month data from an open-label pilot study.
Sara Ellis, Catherine Bostian, Anna Donnelly, Wendy Feng, Katherine Eisen, Melanie Lean, Elizabeth Conlan, Michael Ostacher, Scott T Aaronson, Trisha Suppes
Journal of Affective Disorders June 9, 2025 DOI: 10.1016/j.jad.2025.119655 (opens in new tab) via PubMed
Summary
AI-generated from the abstractAmong veterans with severe treatment-resistant depression, a single 25 mg dose of psilocybin produced significant reductions in depression scores that were sustained for up to 12 months, though antidepressant effects began to wane after 6 months and more substantially after 9 months. At 12 months, 40% of 10 participants maintained a response (≥50% reduction in MADRS) and 30% maintained remission (MADRS ≤10). The study was a small, open-label pilot without a control group, so the findings suggest but do not demonstrate lasting benefit.
Study at a glance
| Characteristics | Open-label pilot study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Veterans with severe treatment-resistant depression |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | 12-month follow-up |
| Topics | Depression Psilocybin |
| Keywords | Long-term outcomes Psychedelics Veterans mental health Psychedelic medicine |
| Citations | 3 |
| Registration | NCT04433858 |
| Key finding | A single 25 mg dose of psilocybin produced significant reductions in depression severity that persisted for 12 months, although the antidepressant effect began to wane after 6 months and more substantially after 9 months. |
Abstract
One-third of Veterans with major depressive disorder suffer from treatment-resistant depression (TRD). This is the first study to evaluate the long-term outcomes of psilocybin in Veterans with severe TRD. This paper presents 12-month results from an open-label pilot study assessing the effects of 25 mg psilocybin in Veterans with severe TRD, defined as a major depressive episode failing to respond to ≥5 treatments, or lasting >2 years. 10 out of 15 participants completed the 12-month follow-up. Depression severity was measured by Montgomery-Åsberg Depression Rating scale (MADRS) at 6, 9, and 12 months posttreatment. Response was defined as ≥50 % reduction in MADRS, and remission as ≤10 MADRS score. Depression scores show significant reductions from baseline across all timepoints. However, there was an increase in MADRS scores from short-term timepoints (Weeks 3 and 12) to Month 12. Of 10 participants, at Month 6, 80 % met response and 50 % met remission criteria for the MADRS. At Month 9, acute responses began to wane. At Month 12, 40 % maintained response and 30 % maintained remission. Limitations include the small sample size and its uncontrolled, unblinded design. In this first-of-kind study on long-term effects of psilocybin for Veterans with severe TRD, depression scores showed significant sustained reductions up to 12-months. However, the antidepressant effects began to wane at 6 months, and then more substantially after 9 months, although these increases in MADRS did not reach statistical significance. Further research is needed. ClinicalTrials.gov Identifier: NCT04433858.