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.