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

Jun 11, 2025Journal of affective disorders

Long-term results of one dose of psilocybin for U.S. military veterans with severe hard-to-treat depression after 12 months

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

At 12 months, 40% of Veterans with severe treatment-resistant depression maintained a response to psilocybin treatment.

Depression severity showed significant reductions from baseline at multiple time points.
At Month 6, 80% of participants met the criteria for response and 50% for remission.
Responses to treatment began to decrease at Month 9, with only 40% maintaining response and 30% maintaining remission at Month 12.
An increase in depression scores was observed from earlier time points to Month 12, although this was not statistically significant.
The study faced limitations including a small sample size and an uncontrolled design.

AI simplified

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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: Limitations include the small sample size and the uncontrolled, unblinded design.

CONCLUSIONS: 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.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04433858.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief