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

This trial (n=59) assessed the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes in depressed patients. Following psilocybin administration at a second session, the therapeutic alliance 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 the endpoint.

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 a 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 a weaker therapeutic alliance.”

Authors: Roberta Murphy, Hannes Kettner, Rick Zeifman, Bruna Giribaldi, Laura Kartner, Johnny Martell, Tim Read, Ashleigh Murphy-Beiner, Michelle Baker-Jones, David J. Nutt, David Erritzoe, Rosalind Watts & Robin L. Carhart-Harris

Study details

Compounds studied
Psilocybin

Participants
59 Humans

Authors

Authors associated with this publication with profiles on Blossom

David Nutt
David 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.

Rosalind Watts
Rosalind Watts is a clinical psychologist and clinical lead at the Psychedelics Research Group at Imperial College London. She is also known for developing the 'Accept, Connect, Embody' psychedelic therapy model.

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).

Michelle Baker Jones
Michelle Baker Jones is an integrative psychotherapeutic counselor and lead guide in the ongoing Imperial College London psychedelic research.

Tim Read
Tim is a psychiatrist and psychotherapist based in London. He is the Lead Supervisor at Synthesis and has had training in holotropic breathwork from Stan Grof.

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Trial of Psilocybin versus Escitalopram for Depression
This 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.