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 Aaronson, Trisha Suppes
Journal of affective disorders June 9, 2025 DOI: 10.1016/j.jad.2025.119655 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.