Trial PaperDepressive DisordersSchizophreniaMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Anxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressPsilocybin

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

This between-subjects study (n=33) investigated whether psilocybin alters emotional processing biases in patients with treatment-resistant depression (TRD) when compared to healthy controls without TRD or psilocybin use. Two sessions of psilocybin with psychological support did improve the processing of emotional faces in treatment-resistant depression and this correlated with reduced anhedonia.

Authors

  • Robin Carhart-Harris
  • David Nutt
  • Robert Leech

Published

Psychopharmacology
individual Study

Abstract

Rationale

Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome.

Objectives

The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients’ emotional processing biases.

Methods

Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin.

Results

We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010).

Conclusions

Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

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Research Summary of 'Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression'

Introduction

Psilocybin, a naturally occurring serotonergic psychedelic, has been investigated for a range of psychiatric indications and prior trials have reported improvements in depressive symptoms, anxiety associated with terminal illness, and substance use disorders when combined with psychological support. Like other classical psychedelics, psilocybin acts primarily via 5-HT2A receptor agonism; the authors note a complex and partly paradoxical literature on 5-HT2A pharmacology and antidepressant mechanisms. Earlier pilot work with psilocybin-assisted therapy produced promising results, but questions remain about durability of effect and reproducibility in treatment-resistant populations. This study extends a previously published pilot by increasing the sample from 12 to 20 patients with treatment-resistant unipolar major depressive disorder and lengthening follow-up to 6 months. The trial aimed to assess safety, tolerability and clinical effects of two supervised oral psilocybin sessions (10 mg then 25 mg, one week apart) delivered within a standardised psychological support model, with the primary clinical endpoint set at 5 weeks post high-dose session using the self-rated QIDS-SR16 as the primary outcome measure.

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