Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
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DOI：
10.1016/s2215-0366(16)30065-7
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发表时间：
2016-07-01
影响因子：
64.3
通讯作者：
Nutt, David J.
中科院分区：
文献类型：
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作者：
Carhart-Harris, Robin L.;Bolstridge, Mark;Nutt, David J.
裸盖菇素是一种5-羟色胺受体激动剂，天然存在于某些蘑菇物种中。最近的研究评估了裸盖菇素对各种疾病的治疗潜力，包括临终焦虑，强迫症，吸烟和酒精依赖，并取得了令人鼓舞的初步结果。在这里，我们的目的是调查的可行性，安全性和有效性的裸盖菇素的患者与单极治疗难治性depression.Methods在这个开放标签的可行性试验，12例（6名男性，6名女性）与中度至重度，单极，难治性抑郁症接受了两个口服剂量的裸盖菇素（10毫克和25毫克，7天间隔）在支持性设置。没有对照组。在每次会议之前，期间和之后提供心理支持。可行性的主要结局指标是患者报告的裸盖菇素效应强度。在给药期间以及随后的门诊和远程随访期间监测患者的不良反应。在治疗后1周至3个月采用标准评定量表对抑郁症状进行评定，以16项抑郁症状快速量表（QIDS）作为主要疗效指标。该试验在ISRCTN注册，编号ISRCTN 14426797。结果裸盖菇素的急性迷幻作用通常在给药后30-60分钟可检测到，在给药后2-3小时达到峰值，并在给药后至少6小时消退至可忽略的水平。低剂量阶段的平均自我评定强度（0-1量表）为0.51（SD 0.36），高剂量阶段为0.75（SD 0.27）。所有患者对裸盖菇素耐受良好，未发生严重或意外不良事件。我们注意到的不良反应是药物发作期间的短暂焦虑（所有患者），短暂的意识模糊或思维障碍（9例患者），轻度和短暂的恶心（4例患者）和短暂的头痛（4例患者）。相对于基线，高剂量治疗后1周（平均QIDS差异-11.8，95% CI-9.15至-14.35，p= 0.002，Hedges' g=3.1）和3个月（-9.2，95% CI -5.69至-12.71，p= 0.003，Hedges' g= 2）抑郁症状显著减轻。显著和持续改善焦虑和快感缺乏也notedia.Interpretation这项研究提供了初步支持的安全性和effi cacy psilocybin治疗难治性抑郁症和动机进一步的试验，更严格的设计，以更好地研究这种方法的治疗潜力。版权所有（C）Carhart-Harris等人。根据CC BY条款分发的开放获取文章。
Background Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.Methods In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary effi cacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.Findings Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0.51 (SD 0.36) for the low-dose session and 0.75 (SD 0.27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11.8, 95% CI-9.15 to -14.35, p= 0.002, Hedges' g=3.1) and 3 months (-9.2, 95% CI -5.69 to -12.71, p= 0.003, Hedges' g= 2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.Interpretation This study provides preliminary support for the safety and effi cacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. Copyright (C) Carhart-Harris et al. Open Access article distributed under the terms of CC BY.