Trial PaperAnxiety DisordersDepressive DisordersPTSDSet & SettingPsilocybin

Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

In a randomised trial of psilocybin-assisted therapy for moderate–severe depression, stronger therapeutic alliance and pre-session rapport predicted larger emotional‑breakthrough and mystical‑type experiences and were associated with greater symptom reduction. Emotional breakthrough during the first session and mystical experience during the second differentially contributed to improvement, while alliance before the second session had an additional direct effect on endpoint depression.

Authors

  • Richard Zeifman
  • Robin Carhart-Harris
  • David Nutt

Published

Frontiers in Pharmacology
individual Study

Abstract

Background

Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes.

Methods

This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder (N= 59). This analysis focused on the psilocybin condition (n= 30), who received two oral doses of 25 mg psilocybin, 3-weeks apart, with psychological preparation, in-session support, and integration therapy. A new psychedelic therapy model, called “Accept-Connect-Embody” (ACE), was developed in this trial. The primary outcome was depression severity 6 weeks post treatment (Quick Inventory of Depressive Symptomatology, QIDS-SR-16). Path analyses tested the hypothesis that therapeutic alliance (Scale To Assess the Therapeutic Relationship Patient Version, STAR-P) would predict depression outcomes via its influence on the acute psychedelic experience, specifically emotional-breakthrough (EBI) and mystical-type experiences (MEQ). The same analysis was performed on the escitalopram arm to test specificity.

Results

The strength of therapeutic alliance predicted pre-session rapport, greater emotional-breakthrough and mystical-type experience (maximum EBI and MEQ scores across the two psilocybin sessions) and final QIDS scores (β= −0.22,R2= 0.42 for EBIMax;β= −0.19,R2= 0.32 for MEQMax). Exploratory path models revealed that final depression outcomes were more strongly affected by emotional breakthrough during the first, and mystical experience during the second session. Emotional breakthrough, but not mystical experience, during the first session had a positive effect on therapeutic alliance ahead of the second session (β= 0.79,p< 0.0001). Therapeutic alliance ahead of the second session had a direct impact on final depression scores, not mediated by the acute experience, with a weaker alliance ahead of the second psilocybin session predicting higher absolute depression scores at endpoint (β= −0.49,p< 0.001)

Discussion

Future research could consider therapist training and characteristics; specific participant factors, e.g., attachment style or interpersonal trauma, which may underlie the quality of the therapeutic relationship, the psychedelic experience and clinical outcomes; and consider how therapeutic approaches might adapt in cases of weaker therapeutic alliance.

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Research Summary of 'Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression'

Introduction

Psychedelic-assisted therapy combines administration of a psychedelic (here, psilocybin) with psychological support. Earlier research has re-established promise for psychedelics across several mental health indications, and prior trials have found that the subjective acute psychedelic experience—most notably mystical-type or peak experiences—predicts therapeutic benefit. More recently, emotional breakthrough (cathartic release or the resolution of difficult emotions) has been proposed as an additional mechanistic pathway, but its role has not been evaluated in a controlled clinical trial. Another widely held but untested assumption in the field is that the therapeutic relationship between participant and guides—the therapeutic alliance and more immediate pre-session rapport—shapes the nature of the acute experience and thereby clinical outcomes. Murphy and colleagues set out to test whether the quality of the therapeutic relationship (measured by the participant-rated STAR-P and a single-item rapport visual analogue scale) predicts depression outcomes via its influence on acute subjective effects (emotional breakthrough, measured by the EBI, and mystical-type experience, measured by the MEQ). Using data from a double-blind randomised controlled trial comparing psilocybin-assisted therapy with escitalopram, the present paper focuses on the psilocybin arm (n = 30) and examines both an overall mediation model using the maximum acute scores across two dosing sessions and exploratory session-specific sequential mediation models.

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Study Details

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