Importance Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression. Objective To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode. Design, Setting, and Participants This was a 12-week, open-label nonrandomized open-label trial conducted at Sheppard Pratt Hospital. Participants aged 18 to 65 years with BDII, a current depressive episode longer than 3 months, and documented insufficient benefit with at least 2 pharmacologic treatments during the current episode were invited to participate. Of 70 approached, 19 met inclusion criteria and were enrolled. The trial was conducted between April 14, 2021, and January 5, 2023. Interventions A single dose of synthetic psilocybin, 25 mg, was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing. Therapists met with patients for 3 sessions during pretreatment, during the 8-hour dosing day, and for 3 integration sessions posttreatment. Main Outcomes and Measures The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures included MADRS scores 12 weeks posttreatment, the self-rated Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR), and the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), each completed at baseline and all subsequent visits. Safety measures included the Columbia Suicide Severity Rating Scale (CSSRS) and the Young Mania Rating Scale (YMRS) completed at each visit. Results Of the 15 participants in this study (6 male and 9 female; mean [SD] age, 37.8 [11.6] years), all had lower scores at week 3, with a mean (SD) change of -24.00 (9.23) points on the MADRS, (Cohen d = 4.08; 95% CI, -29.11 to -18.89; P < .001). Repeat measures analysis of variance showed lower MADRS scores at all tested posttreatment time points, including the end point (Cohen d = 3.39; 95% CI, -33.19 to -16.95; adjusted P < .001). At week 3, 12 participants met the response criterion (50% decrease in MADRS), and 11 met remission criterion (MADRS score ≤10). At the study end point, 12 patients met both response and remission criteria. QIDS-SR scores and Q-LES-Q-SF scores demonstrated similar improvements. YMRS and CSSRS scores did not change significantly at posttreatment compared to baseline. Conclusions and Relevance The findings in this open-label nonrandomized open-label trial suggest efficacy and safety of psilocybin with psychotherapy in BDII depression and supports further study of psychedelics in this population.

中文翻译：

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单剂量合成裸盖菇素联合心理疗法治疗难治性双相 II 型重性抑郁发作：一项非随机开放标签试验。


重要性 II 型双相情感障碍 (BDII) 是一种使人衰弱的疾病，通常与难以治疗的抑郁发作相关。有证据表明裸盖菇素具有快速抗抑郁作用，但尚未在双相抑郁症中进行研究。目的 确定裸盖菇素对当前抑郁发作的 BDII 患者的安全性和有效性。设计、设置和参与者 这是一项在 Sheppard Pratt 医院进行的为期 12 周的开放标签非随机开放标签试验。邀请年龄为 18 至 65 岁、患有 BDII、当前抑郁发作时间超过 3 个月、且在当前发作期间至少接受过 2 种药物治疗但疗效不足的参与者参加。在 70 名接触者中，有 19 名符合纳入标准并被登记。该试验于 2021 年 4 月 14 日至 2023 年 1 月 5 日期间进行。 干预措施 给予单剂量的合成裸盖菇素 25 毫克。服药前至少两周停用精神药物。在治疗前、每天 8 小时给药期间以及治疗后 3 次整合治疗期间，治疗师与患者会面 3 次。主要结果和测量 主要结果测量是治疗后 3 周蒙哥马利-阿斯伯格抑郁评定量表 (MADRS) 的变化。次要指标包括治疗后 12 周的 MADRS 评分、自评抑郁症状快速清单 - 自我评分 (QIDS-SR) 以及自评生活质量享受和满意度问卷 - 简表 (Q-LES-Q-SF) ），每一项均在基线和所有后续访问中完成。安全措施包括每次就诊时完成的哥伦比亚自杀严重程度评定量表（CSSRS）和青年躁狂评定量表（YMRS）。 结果 本研究的 15 名参与者（6 名男性和 9 名女性；平均 [SD] 年龄为 37.8 [11.6] 岁）在第 3 周时的得分均较低，平均 (SD) 变化为 -24.00 (9.23) 分在 MADRS 上，（Cohen d = 4.08；95% CI，-29.11 至 -18.89；P < .001）。重复测量方差分析显示，在所有测试的治疗后时间点（包括终点）MADRS 评分较低（Cohen d = 3.39；95% CI，-33.19 至 -16.95；调整后 P < .001）。第 3 周，12 名参与者达到缓解标准（MADRS 下降 50%），11 名参与者达到缓解标准（MADRS 评分≤10）。在研究结束时，12 名患者同时满足缓解和缓解标准。 QIDS-SR 分数和 Q-LES-Q-SF 分数表现出类似的改进。与基线相比，治疗后 YMRS 和 CSSRS 评分没有显着变化。结论和相关性 这项开放标签非随机开放标签试验的结果表明裸盖菇素联合心理治疗治疗 BDII 抑郁症的有效性和安全性，并支持在该人群中进一步研究迷幻药。