This pre-print analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.
Abstract of Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression
“Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two groups with major depressive disorder: 1) a ‘psilocybin group’ that received two dosing sessions with 25mg plus six weeks of daily placebo, and 2) an ‘escitalopram group’ that received six weeks of the SSRI escitalopram, plus two dosing sessions with an inactive/placebo dose of 1mg psilocybin. Both groups had an equal amount of psychological support throughout. An emotional face fMRI paradigm was completed at baseline (pre-treatment) and at the six-week post-treatment primary endpoint (three weeks following psilocybin dosing sessions). An analysis examining the interaction between patient group (psilocybin vs. escitalopram) and time-point (pre-vs. post-treatment) showed a robust effect in a distributed network of cortical brain regions. Follow-up analyses showed that post-treatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change, or even a slight increase, in the psilocybin group. Specific analyses of the amygdala showed a reduction of response to fear faces in the escitalopram group, but no effects for the psilocybin group. Despite large improvements in depressive symptoms in the psilocybin group, psilocybin-therapy had only a minor effect on brain responsiveness to emotional stimuli. We suggest that reduced emotional responsiveness may be a biomarker of SSRIs’ antidepressant action that is not shared by psilocybin-therapy.”
Authors: Matthew B. Wall, Lysia Demetriou, Bruna Giribaldi, Leor Roseman, Natalie Ertl, David Erritzoe, David J. Nutt & Robin L. Carhart-Harris
Summary of Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression
Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments. fMRI was used to assess neural responses to emotional faces in two groups with major depressive disorder: a psilocybin group that received two dosing sessions with 25mg plus six weeks of daily placebo, and an escitalopram group. Despite large improvements in depressive symptoms, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli.
Major Depressive Disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders. SSRIs are a popular treatment option, but are moderately effective and have acceptability rates comparable with placebo.
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https://doi.org/10.1101/2023.05.29.23290667
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Cite this paper (APA)
Wall, M. B., Demetriou, L., Giribaldi, B., Roseman, L., Ertl, N., Erritzoe, D., ... & Carhart-Harris, R. L. (2023). Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression. medRxiv, 2023-05.
Study details
Compounds studied
Psilocybin
Topics studied
Depression
Neuroscience
Study characteristics
Original Re-analysis
Placebo-Controlled
Active Placebo
Double-Blind
Randomized
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.
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
Imperial College LondonThe Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 25 mg | 2xLinked Research Papers
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Trial of Psilocybin versus Escitalopram for Depression
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