Center for Psychedelic and Consciousness Research, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.
College of Social Work, The Ohio State University, Columbus.
JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.
Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.
To investigate the effect of psilocybin therapy in patients with MDD.
DESIGN, SETTING, AND PARTICIPANTS: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).
Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.
The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).
Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).
Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.
ClinicalTrials.gov Identifier: NCT03181529.
重要性：重度抑郁症（MDD）是一个重大的公共卫生负担，但目前的治疗方法效果有限，且患者的依从性也较差。最近的证据表明，1 或 2 次使用致幻蘑菇加上心理支持，可以在癌症患者和治疗抵抗性抑郁症患者中产生抗抑郁作用。
目的：调查迷幻蘑菇疗法治疗 MDD 的效果。
设计、地点和参与者：这是一项在马里兰州巴尔的摩市约翰霍普金斯湾景医疗中心的迷幻药和意识研究中心进行的随机、等待名单对照临床试验。年龄在 21 至 75 岁之间、患有 MDD 诊断、目前未使用抗抑郁药物、没有精神障碍、严重自杀企图或住院史的成年人有资格参加。招募工作于 2017 年 8 月至 2019 年 4 月进行，主要结局评估于 2019 年 7 月完成。共有 27 名参与者被随机分配到即刻治疗组（n = 15）或延迟治疗组（等待名单对照组；n = 12）。数据分析于 2019 年 7 月 1 日至 2020 年 7 月 31 日进行，包括完成干预措施的参与者（可评估人群）。
干预措施：在支持性心理治疗的背景下（约 11 小时），给予两次致幻蘑菇治疗（第 1 次：20mg/70kg；第 2 次：30mg/70kg）。参与者被随机分为立即开始治疗或延迟 8 周后开始治疗。
主要结局和测量指标：主要结局是使用 GRID-Hamilton 抑郁评定量表（GRID-HAMD）评分评估抑郁严重程度，在延迟治疗组中在基线时（≥17 分才可入组）和入组后第 5 周及第 8 周进行评估，对应于即刻治疗组中干预后第 1 周和第 4 周进行评估。次要结局包括快速抑郁症状自评量表（QIDS-SR）。
结果：在随机分组的参与者中，27 名中有 24 名（89%）完成了干预和第 1 周及第 4 周的治疗后评估。这一人群的平均（SD）年龄为 39.8（12.2）岁，其中 16 名女性（67%），基线时的平均（SD）GRID-HAMD 评分为 22.8（3.9）。即刻治疗组在第 1 周和第 4 周的平均（SD）GRID-HAMD 评分分别为 8.0（7.1）和 8.5（5.7），明显低于延迟治疗组在第 5 周和第 8 周的可比时间点的评分，分别为 23.8（5.4）和 23.5（6.0）。第 5 周时的效应量较大（Cohen d=2.5；95%CI，1.4-3.5；P<0.001），第 8 周时的效应量也较大（Cohen d=2.6；95%CI，1.5-3.7；P<0.001）。QIDS-SR 记录了从第 1 次治疗后的第 1 天到第 1 天，平均（SD）抑郁评分从基线时的 16.7（3.5）降低到 6.3（4.4）（Cohen d=2.6；95%CI，1.8-3.5；P<0.001），这一降低一直持续到第 4 周的随访（6.0[5.7]；Cohen d=2.3；95%CI，1.5-3.0；P<0.001）。在总体样本中，第 1 周有 17 名（71%）参与者和第 4 周有 17 名（71%）参与者对干预有明显的反应（GRID-HAMD 评分降低≥50%），第 1 周有 14 名（58%）参与者和第 4 周有 13 名（54%）参与者达到缓解（GRID-HAMD 评分≤7）。
结论和相关性：结果表明，迷幻蘑菇与治疗相结合在治疗 MDD 方面是有效的，从而扩展了之前对癌症和抑郁症患者进行这项干预以及对治疗抵抗性抑郁症患者进行非随机研究的结果。
试验注册：ClinicalTrials.gov 标识符：NCT03181529。
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