A multicentre clinical trial led by COMPASS Pathways across 22 international sites including Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust has found that a single 25mg dose of COMP360 psilocybin, alongside psychological support, had a significant impact in reducing symptoms of depression in participants with treatment-resistant depression.
Approximately 100 million people in the world suffer with treatment-resistant depression, which means they have not responded to at least two antidepressant treatments for their major depressive disorder.
The study, published in the New England Journal of Medicine, investigated the change from baseline in the severity of depression, as assessed using the Montgomery–Åsberg Depression Rating Scale, in participants with treatment-resistant depression over the course of 12 weeks following a single dose of COMP360 psilocybin alongside psychological support. Researchers found that participants reported a greater reduction in depression scores three weeks after taking a single 25 mg dose of COMP360 psilocybin compared to those who took the lowest 1 mg dose.
Some adverse effects, such as headaches, nausea, dizziness, fatigue, and thoughts around suicide, were reported across all dose groups.
This phase 2b clinical trial was conducted at 22 sites in 10 countries across Europe (Czech Republic, Denmark, Germany, Ireland, the Netherlands, Portugal, Spain, and the United Kingdom) and North America (Canada and the United States) between 1 March 2019 and 27 September 2021. 233 participants with treatment-resistant depression were allocated at random to receive a single 25 mg, 10 mg, or 1 mg dose of COMP360 psilocybin, along with psychological support; with those who received the 1 mg dose acting as a control group. Neither the participants nor the researchers were aware which dose the participant had received.
Dr James Rucker, Consultant Psychiatrist & Lead for the Psychoactive Trials Group at IoPPN, at King’s College London and South London and Maudsley NHS Foundation Trust, who took part in the research said:
‘Whilst many patients with mental health problems get better with available treatments, a subgroup of patients do not even though they try many different forms of treatment. This is sometimes called ‘treatment resistance’. This can lead to a variety of other problems that seriously impact on patients and the people around them. Treatment options are often limited, coming with troublesome side effects and/or stigma. Therefore, new paradigms of treatment are needed, and clinical research of new treatments is important. Psilocybin therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials. We are doing this work at the Psychoactive Trials Group, and we deliver new and pioneering treatments in collaboration with our colleagues at the Maudsley Centre for Advanced Treatments.’
‘This study, which is by far the largest clinical trial on the use of psilocybin for treatment-resistant depression to date, demonstrated that a single 25 mg dose of psilocybin improved participants’ symptoms of depression in comparison to a 1 mg dose (control). These findings are a positive step in the right direction. Our task now is to investigate psilocybin for treatment-resistant depression in larger clinical trials with more participants, comparing it both to placebo and to established treatments.’
‘The publication of our COMP360 psilocybin therapy study in the most prestigious peer-reviewed medical journal in the world is a proud moment for everyone involved,’ said Professor Guy Goodwin, Chief Medical Officer, COMPASS Pathways. ‘We saw positive results in a particularly difficult to treat group of patients, and the highest dose of COMP360 psilocybin had the greatest impact on people’s depression. This suggests that COMP360 psilocybin has a true pharmacological effect, a finding that is critical for it to be recognised as a new treatment option in the future. We look forward to starting our phase 3 programme later this year, moving us closer to providing COMP360 psilocybin with psychological support for patients who desperately need it.’
All participants were assessed on the severity of their depressive symptoms the day before the COMP360 psilocybin was administered, and follow up assessments were conducted on day two, and weeks one, three, six, nine, and 12.
Participants were given COMP360 psilocybin in specialised rooms designed to provide a nonclinical and calming atmosphere. The psychedelic effects lasted between 6 to 8 hours, and during this time an experienced therapist was in the room to provide psychological support. All therapists underwent a detailed training programme designed for the trial. After the psychedelic effects were fully dissipated participants were able to return home.
Researchers found that participants who received the 25 mg dose of COMP360 psilocybin, with psychological support, experienced a rapid and greater reduction in depression scores than those who received the 1 mg control dose (p<0.001).
Over the 12-week study period adverse effects, including headache, nausea, dizziness, and fatigue, occurred in 84% of participants in the 25 mg dose group, 75% in the 10 mg dose group, and 72% in the 1 mg dose group. Suicidal ideation and intentional self-injury were seen in all dose groups, as is common in treatment-resistant depression studies. Most cases occurred more than a week after the COMP360 psilocybin session. There was no mean worsening of suicidal ideation scores on the MADRS scale in any dose group. Suicidal behaviours were reported at least one month after COMP360 administration for three non-responders in the 25mg group.
The trial was designed and funded by COMPASS Pathways. It was conducted in collaboration with the Psychoactive Trials Group at the IoPPN and the South London and Maudsley NHS Foundation Trust.
For further information please contact: Patrick O’Brien, Senior Media Officer, IoPPN King’s College London Tel: +44 7813706151 Em: email@example.com
‘Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression’ Goodwin et al is published in New England Journal of Medicine on 2 November 2022 5pm ET/9pm GMT DOI: 10.1056/NEJMoa2206443
Link to publication when embargo lifts http://www.nejm.org/doi/full/10.1056/NEJMoa2206443
About King’s College London
King's College London is one of the top 35 universities in the world and one of the top 10 in Europe (QS World University Rankings, 2021/22) and among the oldest in England. King's has more than 33,000 students (including more than 12,800 postgraduates) from over 150 countries worldwide, and 8,500 staff. King's has an outstanding reputation for world-class teaching and cutting-edge research.
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.
About COMPASS Pathways
COMPASS Pathways plc (Nasdaq: CMPS) is a mental health care company dedicated to accelerating patient access to evidence-based innovation in mental health. Our focus is on improving the lives of those who are suffering with mental health challenges and who are not helped by current treatments. We are pioneering the development of a new model of psilocybin therapy, in which our proprietary formulation of synthetic psilocybin, COMP360, is administered in conjunction with psychological support. COMP360 has been designated a Breakthrough Therapy by the US Food and Drug Administration (FDA) and has received Innovative Licensing and Access Pathway (ILAP) designation in the UK for treatment-resistant depression (TRD). We have completed a phase 2b clinical trial of psilocybin therapy for TRD, in 22 sites across Europe and North America. This was the largest randomised, controlled, double-blind psilocybin therapy clinical trial ever conducted, and our topline data showed a statistically significant (p<0.001) and clinically relevant improvement in depressive symptom severity after three weeks for patients who received a single high dose of COMP360 psilocybin with psychological support. We are also running phase 2 clinical trials of COMP360 psilocybin therapy for post-traumatic stress disorder (PTSD) and anorexia nervosa. COMPASS is headquartered in London, UK, with offices in New York and San Francisco in the US. Our vision is a world of mental wellbeing. www.compasspathways.com
New England Journal of Medicine
Method of Research
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Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
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The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health or Care Research, or the Department of Health and Social Care in the United Kingdom. Supported by COMPASS Pathfinder. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. We thank the participants, without whom this research would not have been possible; the following staff members at COMPASS Pathfinder and Worldwide Clinical Trials for their contributions: Molly Lennard-Jones, Rachel Winzer, Batya Septimus, Merve Atli, Ozlem Redjep, Hannah Tadley, Nisha Thiara, Hollie Simmons, Julia Forte, Niccolo Bassani, and Alexandra Novikova; Edward Schweizer for helping with the first draft of the manuscript; Megan Croal for helping revise subsequent drafts; the staff at all the sites for help with recruitment of participants, including the Champalimaud Foundation (Portugal), Hospital del Mar (Spain), Leiden UMC (the Netherlands), and St. Pancras Clinical Research (United Kingdom); and Bill Richards, Mike Emmanuel, and Mary Johnson for their advice in designing the trial originally.