VA Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
VA Palo Alto Health Care System, Palo Alto, CA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
J Affect Disord. 2025 Jan 15;369:381-389. doi: 10.1016/j.jad.2024.09.133. Epub 2024 Sep 27.
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.
退伍军人常患有持久且严重的抑郁症，这给他们带来了极大的痛苦，并与高自杀率和残疾率相关。这是第一项评估迷幻蘑菇在患有严重治疗抵抗性抑郁症（TRD）的退伍军人中的疗效和安全性的研究。
15 名患有严重 TRD（重度抑郁发作经 5 种以上治疗或持续>2 年仍未缓解）的退伍军人接受了 25mg 迷幻蘑菇治疗。主要结局为治疗后 3 周时蒙哥马利-阿斯伯格抑郁评定量表（MADRS）的变化。反应定义为 MADRS 降低≥50%，缓解定义为 MADRS 评分≤10。使用五维度改变意识状态量表（5D-ASC）评估迷幻体验。安全性评估包括自杀意念和不良反应的评估。服用抗抑郁药的患者逐渐减少剂量以避免药物相互作用。
15 名参与者中，60%在第 3 周时达到反应标准，53%达到缓解标准。在 12 周时，47%维持反应，40%缓解。共病 PTSD 并未显著影响研究结果。5D-ASC 报告的迷幻体验与反应无相关性。被判断需要抗抑郁药的参与者从该时间点开始重新服用，并被视为无反应者（n=4）。未发生意外不良反应。
局限性包括样本量小，以及研究的非对照和非盲法性质。
在这项针对患有严重 TRD 的退伍军人的迷幻蘑菇的首次研究中，观察到了惊人的反应和缓解率。许多退伍军人患有 PTSD，但未观察到反应的调节作用。迷幻体验的程度与抑郁变化无关。需要进一步研究。
ClinicalTrials.gov 标识符：NCT04433858。
