Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study.

In a small, uncontrolled trial, 15 veterans with severe treatment-resistant depression received a single 25 mg dose of psilocybin. At three weeks, 60% met criteria for response and 53% for remission. By twelve weeks, 47% maintained response and 40% remission. Co-occurring PTSD did not affect outcomes, and the intensity of the psychedelic experience did not correlate with depression improvement. Four participants who needed to restart antidepressants were counted as non-responders from that point. No unexpected adverse events occurred. The authors note limitations including the small sample and lack of a control group, and call for further study.

Study at a glance

Abstract

The enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD). 15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions. Of 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred. Limitations include the small sample size, and the uncontrolled and unblinded nature of the study. In this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted. ClinicalTrials.gov Identifier: NCT04433858.