This preprint (2022) reanalyses the data of a clinical trial in which the effects of psilocybin were compared to that of the SSRI escitalopram for major depressive disorder. Bayesian reanalysis found indeterminate evidence that psilocybin is superior that escitalopram using the QIDS SR-16 while strong evidence favoured psilocybin when using the BDI-1D and MADRS and extremely strong evidence when using the HAMD-17. These results, and other findings, support the idea that psilocybin outperformed escitalopram but was not clinically meaningful and, psilocybin is almost certainly non-inferior to escitalopram.
Abstract
“Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.
Design: Reanalysis of a two-arm double-blind placebo-controlled trial.
Participants: Fifty-nine patients with MDD. Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups. Outcome measures: Quick Inventory of Depressive Symptomatology–Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.
Results: Using Bayes factors and ‘sceptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature-defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board, we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.
Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful—-and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.”
Authors: Sandeep Nayak, Bilal A. Bari, David B. Yaden, Meg J. Spriggs, Fernando Rosas, Joesph M. Peill, Bruna Giribaldi, David Erritzoe, David J. Nutt & Robin Carhart-Harris
Summary of A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression
Introduction
A recent trial investigating psilocybin’s efficacy, relative to escitalopram, for major depressive disorder reported no significant benefit relative to the standard of care. However, psilocybin significantly outperformed escitalopram on all secondary outcomes, including three clinically-validated depression scales.
Frequentist and Bayesian Approaches in Clinical Trials
Carhart-Harris et al. (2021) highlight several drawbacks of frequentist methods, including multiple comparisons, p-values not conveying the probability of any particular hypothesis, rigid separation of hypothesis testing from effect size estimation, and fixed sample sizes chosen on the basis of a priori assumptions about the true effect size.
Find this paper
A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression
https://doi.org/10.31234/osf.io/sb5ur
Open Access | Google Scholar | Backup | 🕊
Study details
Compounds studied
Psilocybin
Topics studied
Depression
Study characteristics
Placebo-Controlled
Double-Blind
Participants
59
Humans
Authors
Authors associated with this publication with profiles on Blossom
David NuttDavid John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.
David Yaden
David Bryce Yaden (Ph.D.) is a Research Fellow at Johns Hopkins University School of Medicine. His research focus is on the psychology, neuroscience, and psychopharmacology of psychedelics and other positively transformative experiences. Specifically, David is interested in understanding how brief experiences can result in such long-term changes to well-being.
Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.
David Erritzoe
David Erritzoe is the clinical director of the Centre for Psychedelic Research at Imperial College London. His work focuses on brain imaging (PET/(f)MRI).
Institutes
Institutes associated with this publication
Johns Hopkins UniversityJohns Hopkins University (Medicine) is host to the Center for Psychedelic and Consciousness Research, which is one of the leading research institutes into psychedelics. The center is led by Roland Griffiths and Matthew Johnson.
Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.
Linked Research Papers
Notable research papers that build on or are influenced by this paper
Trial of Psilocybin versus Escitalopram for DepressionThis double-blind placebo-controlled study (n=59) compared psilocybin (2x25mg; 3 weeks apart) to escitalopram (SSRI) over a six-week period and found large improvements in depression scores for those suffering from depression (MDD) in both groups. On the main measure of depression, the QIDS-SR-16, there was no significant difference between both groups. The study did find significant differences, favoring psilocybin, on the HAM-D-17, MADRS, avoidance, flourishing, wellbeing, and suicidality.