Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial

Abstract

Introduction: Psilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials. In this trial (short name: PsiDeR) we aimed to test the feasibility of a parallel-group, randomised, placebo-controlled design. The primary outcomes in this trial are measures of feasibility: recruitment rates, dropout rates and the variance of the primary outcome measure of depression.

Methods and analysis: We are recruiting up to 60 participants at a single centre in London, UK who are unresponsive to, or intolerant of, at least two evidence-based treatments for MDD. Participants are randomised to receive a single dosing session of 25 mg psilocybin or a placebo. All participants receive a package of psychological therapy. The primary outcome measure for depression is the Montgomery Asberg Depression Rating Scale collected by blinded, independent raters. The primary endpoint is at 3 weeks, and the total follow-up is 6 weeks. With further informed consent, this study collects neuroimaging and omics data for mechanism and biomarker analyses and offers participants an open label extension consisting of a further, open label dose of 25 mg of psilocybin.

Ethics and dissemination: All participants will be required to provide written informed consent. The trial has been authorised by the National Research Ethics Committee (20-LO/0206), Health Research Authority (252750) and Medicine's and Healthcare Products Regulatory Agency (CTA 14523/0284/001-0001) in the UK. Dissemination of results will occur via a peer-reviewed publication and other relevant media.

Trial registration numbers: EUDRACT2018-003573-97; NCT04959253.

Keywords: adult psychiatry; clinical trials; depression & mood disorders.

Conflict of interest statement

Competing interests: JR is an honorary consultant psychiatrist at The South London & Maudsley NHS Foundation Trust, a consultant psychiatrist at Sapphire Medical Clinics and an NIHR Clinician Scientist Fellow at the Centre for Affective Disorders at King’s College London. JR’s salary is funded by a fellowship (CS-2017-17-007) from the National Institute for Health Research (NIHR). JR leads the Psychedelic Trials Group with Professor Allan Young at King’s College London. King’s College London receives grant funding from COMPASS Pathways PLC and Beckley PsyTech to undertake phase 1 and phase 2 trials with psychedelics, including psilocybin. COMPASS Pathways PLC has paid for James Rucker to attend trial related meetings and conferences to present the results of research using psilocybin. COMPASS Pathways provided the psilocybin and placebo capsules for this trial, without charge. JR asserts that COMPASS Pathways had no influence over the content of this article or the design of this trial. JR has undertaken paid consultancy work for Beckley PsyTech and Clerkenwell Health. Payments for consultancy work are received and managed by King’s College London. James Rucker does not benefit personally. JR has no shareholdings in pharmaceutical companies. Allan H Young. Employed by King’s College London; Honorary Consultant SLaM (NHS UK). Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS. Consultant to Johnson & Johnson. Consultant to Livanova. Received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova. Principal Investigator in the Restore-Life VNS registry study funded by LivaNova. Principal Investigator on ESKETINTRD3004: 'An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression'. Principal Investigator on 'The Effects of Psilocybin on Cognitive Function in Healthy Participants'. Principal Investigator on 'The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)'. Grant funding (past and present): 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). Janssen (UK). No shareholdings in pharmaceutical companies. All other authors declare no competing interests.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Trial Schematic. Blue, red and black lines represent in-person visits. Green lines represent a flexible visit schedule of psychological preparation, which may be undertaken remotely. Red lines represent dosing sessions. Dosing session at OLE2 consists of 25 mg of psilocybin for all eligible and consenting participants. Black line represents the primary end point (3 weeks after V3). PS, prescreening.