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Clinical Trial
. 2023 Apr 14:327:120-127.
doi: 10.1016/j.jad.2023.01.108. Epub 2023 Feb 4.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life

Guy M Goodwin  1 , Scott T Aaronson  2 , Oscar Alvarez  3 , Merve Atli  4 , James C Bennett  4 , Megan Croal  4 , Charles DeBattista  5 , Boadie W Dunlop  6 , David Feifel  7 , David J Hellerstein  8 , Muhammad Ishrat Husain  9 , John R Kelly  10 , Molly R Lennard-Jones  4 , Rasmus W Licht  11 , Lindsey Marwood  4 , Sunil Mistry  4 , Tomáš Páleníček  12 , Ozlem Redjep  4 , Dimitris Repantis  13 , Robert A Schoevers  14 , Batya Septimus  4 , Hollie J Simmons  4 , Jair C Soares  15 , Metten Somers  16 , Susan C Stansfield  4 , Jessica R Stuart  4 , Hannah H Tadley  4 , Nisha K Thiara  4 , Joyce Tsai  4 , Mourad Wahba  17 , Sam Williams  4 , Rachel I Winzer  4 , Allan H Young  18 , Matthew B Young  4 , Sid Zisook  19 , Ekaterina Malievskaia  4
Affiliations
Free article
Clinical Trial

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life

Guy M Goodwin et al. J Affect Disord. .
Free article

Abstract

Background: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints.

Methods: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function.

Results: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures.

Limitations: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin.

Conclusions: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

Keywords: Antidepressant; Anxiety; Patient-reported outcomes; Psilocybin; Psychedelic; Treatment-resistant depression.

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Conflict of interest statement

Conflict of interest GMG is emeritus NIHR Senior Investigator and has consulted for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVApharm, H Lundbeck A/S, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda and WebMD. STA has consulted for COMPASS Pathways, Genomind, Janssen Global Services, LivaNova, Neuronetics, and Sage Therapeutics. CD has consulted for AbbVie and Corcept Therapeutics. CD has received grant funding from Beckley Psytech, Relmada Therapeutics, and Sage Therapeutics. BWD has consulted for Cerebral Therapeutics, Greenwich Biosciences, Myriad Genetic Laboratories, Otsuka America Pharmaceutical, Sage Therapeutics, and Sophren Therapeutics. BWD has received grant funding from Boehringer Ingelheim, COMPASS Pathways, Otsuka America Pharmaceutical, and the Usona Institute. DF has received grant funding from MindMed, Neurolief, Perception Neuroscience, and Relmada Therapeutics. DF holds a patent for psychedelic drug treatment of neuropsychiatric disorders and cerebral palsy. DJH has consulted for Reset Pharmaceuticals. DJH has received grant funding from Assurex, Intra-Cellular Therapies, Marinus Pharmaceuticals, COMPASS Pathways, Relmada Pharmaceuticals, and Beckley Foundation. MIH owns shares in Mindset Pharma. MIH has received consultancy fees from Psyched Therapeutics and the Wake Network. JRK has consulted for Clerkenwell Health and has received grant funding from the Health Research Board (ILP-POR-2022-030). RWL has participated in speaking engagements for H Lundbeck A/S, Janssen Global Services, and Teva Pharmaceuticals. TP has consulted for Atai Life Sciences, CB21 Pharma, and GH Research. TP is a principal investigator at Ketabon GmbH and MAPS Europe BV. TP is a fiduciary officer at the PSYRES Foundation, Psyon, and the Society for the Promotion of Neuroscience Research. DR is honorary board chair of the nonprofit organization MAPS Deutschland. RAS has consulted for Clexio Biosciences and GH Research and has received grant funding from Janssen Pharmaceuticals. JCS has consulted for Alkermes, Johnson & Johnson, and Merck. JCS has received grant funding from MindMed and Relmada Therapeutics. MW and SZ have participated in speaking engagements for COMPASS Pathways and Janssen Pharmaceuticals. GMG, JT, LM, NKT, OR, SS, BS, HHT, SW, and EM own shares in COMPASS Pathways. GMG, MA, JCB, MC, MRL-J, EM, LM, SM, OR, BS, HJS, JRS, HHT, NKT, JT, RIW, MBY, SCS, SW, and EM are current or past employees of COMPASS Pathways. OA, BWD, CD, DF, MIH, DJH, JCS, and SZ have received grant funding from COMPASS Pathways. STA, OA, CD, BWD, DF, DJH, MIH, JRK, RWL, TP, DR, RAS, JCS, MS, MW, AHY, and SZ were site investigators or sub-investigators for COMPASS Pathways during the clinical trial and received funding to conduct the study. AHY is employed by King's College London; Honorary Consultant South London and Maudsley NHS Foundation Trust (NHS UK). AHY was editor of Journal of Psychopharmacology and Deputy Editor for BJPsych Open. AHY participated in paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS Pathways, Sage, Novartis, Neurocentrx. AHY was principal investigator in the Restore-Life VNS registry study funded by LivaNova, ESKETINTRD3004 funded by Janssen Research & Development, LLC, and “The Effects of Psilocybin on Cognitive Function in Healthy Participants”. AHY is principal investigator for Novartis MDD study MIJ821A12201 and additional studies for COMPASS Pathways. AHY has received grant funding from NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK); and Janssen (UK) EU Horizon 2020. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

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