Trial PaperDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Set & SettingPsilocybin

Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study

This qualitative study of 11 patients with treatment‑resistant depression who received a single psilocybin session identified three core themes—trust and expectation management, navigating the acute experience, and the need for more comprehensive care. Patients’ accounts suggest that optimising set and setting through individualised preparation, sustained therapeutic relationships, and offering additional sessions could improve safety, effectiveness and real‑world adoption of psilocybin treatment.

Authors

  • Robert Schoevers
  • Jeanine Kamphuis
  • Eric Vermetten

Published

Scientific Reports
individual Study

Abstract

Psilocybin is the most researched classic psychedelic for Treatment-Resistant Depression (TRD). While optimizing set and setting are considered essential for efficacy and safety, patient perspectives on these aspects have rarely been investigated. To address this knowledge gap, the current paper explored the experiences of 11 TRD patients (8 women, 3 men) participating in a double-blind randomized clinical trial with a single session of oral (1, 10 or 25 mg) psilocybin treatment. After qualitative analysis, three major themes were identified: (1) challenges with trust-building and expectation management; (2) navigating the experience; and (3) the need for a more comprehensive treatment. Subthemes of the first theme include a general distrust in mental healthcare, trust in study therapists, limited time for preparation, and managing expectations. The second theme included the following subthemes: trusting to surrender, profound and overwhelming experiences, and music as a guide. The third theme addressed a desire for multiple psilocybin sessions, and challenges with sensemaking. Patients’ perspectives provided important insights into potential optimization of psilocybin treatment of TRD, including individualized preparation, investment in trust-building, offering additional psilocybin sessions, providing access to sustained (psycho)therapy with trusted therapists, and personalizing treatment approaches, which may also enhance real-world adaption of these treatments.

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Research Summary of 'Patient perspectives and experiences with psilocybin treatment for treatment-resistant depression: a qualitative study'

Introduction

Depression is a prevalent disorder with substantial unmet need: up to 30% of patients do not respond adequately to standard treatments. Classic psychedelics, and psilocybin in particular, have re-emerged as candidate therapeutics for major depressive disorder and treatment-resistant depression (TRD). Clinical trials to date have administered one or two doses (commonly 10–30 mg) and reported rapid, sometimes sustained, reductions in depressive symptoms, but qualitative research on patients' subjective experiences and on contextual factors (set and setting) remains limited. This study aimed to fill that gap by exploring expectations and lived experiences of TRD patients who participated in a double-blind, randomized, dose-finding Phase 2b trial of a single oral psilocybin session (1 mg active control, 10 mg, or 25 mg). Using in-depth interviews and an Interpretative Phenomenological Analysis framework, the investigators sought to identify themes about preparation, the dosing experience, and integration that could inform optimisation of psilocybin treatment for this vulnerable population.

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Study Details

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