Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

被引:976
作者
Carhart-Harris, Robin L. [1 ]
Bolstridge, Mark [1 ]
Rucker, James [1 ,3 ]
Day, Camilla M. J. [1 ]
Erritzoe, David [1 ]
Kaelen, Mendel [1 ]
Bloomfield, Michael [5 ]
Rickard, James A. [8 ]
Forbes, Ben [4 ]
Feilding, Amanda [9 ]
Taylor, David [2 ]
Pilling, Steve [6 ]
Curran, Valerie H. [7 ]
Nutt, David J. [1 ]
机构
[1] Imperial Coll London, Fac Med, Div Brain Sci, Ctr Neuropsychopharmacol, London W12 0NN, England
[2] South London & Maudsley NHS Fdn Trust, Dept Pharm & Pathol, London, England
[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England
[4] Kings Coll London, Inst Pharmaceut Sci, London, England
[5] UCL, Dept Psychiat, London, England
[6] UCL, Clin Psychol & Clin Effectiveness, London, England
[7] UCL, Clin Psychopharmacol Unit, London, England
[8] Barts Hlth NHS Trust, Barts Hlth Pharmaceut, Royal London Hosp, London, England
[9] Beckley Fdn, Beckley Pk, Oxford, England
基金
英国医学研究理事会;
关键词
LYSERGIC-ACID DIETHYLAMIDE; 5-HT2A RECEPTOR; LSD;
D O I
10.1016/S2215-0366(16)30065-7
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
引用
收藏
页码:619 / 627
页数:9
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