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

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Title: Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
Author(s): Carhart-Harris, RL
Bolstridge, M
Rucker, J
Day, CM
Erritzoe, D
Kaelen, M
Bloomfield, M
Rickard, JA
Forbes, B
Feilding, A
Taylor, D
Pilling, S
Curran, VH
Nutt, DJ
Item Type: Journal Article
Abstract: 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.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 psilocybins 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 efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.Psilocybins 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.This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.Medical Research Council.
Publication Date: 17-May-2016
Date of Acceptance: 1-Apr-2016
URI: http://hdl.handle.net/10044/1/33092
DOI: https://dx.doi.org/10.1016/S2215-0366(16)30065-7
ISSN: 2215-0374
Publisher: Elsevier
Start Page: 619
End Page: 627
Journal / Book Title: Lancet Psychiatry
Volume: 3
Issue: 7
Copyright Statement: © Carhart-Harris et al. 2016. Open Access article distributed under the terms of CC BY.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/J00460x/1
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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