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The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder

Adam W. Levin, Rafaelle Lancelotta, Nathan D. Sepeda, Natalie Gukasyan, Sandeep M. Nayak, Theodore L Wagener, Frederick S. Barrett, Roland R. Griffiths, Alan K. Davis

PLoS One March 14, 2024 DOI: 10.1371/journal.pone.0300501 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 24
Population Adults with major depressive disorder
Intervention Psilocybin-assisted therapy
Dose 20mg/70kg and 30mg/70kg
Duration 12-month follow-up
Topics Psychedelic-assisted therapy Depression Psilocybin
Keywords Psilocybin research Therapeutic relationships Mental health Depression treatment
Citations 65
Registration NCT03181529
Key findings A stronger therapeutic alliance before and after psilocybin sessions predicted lower depression scores up to 12 months later, and was correlated with more intense mystical experiences and psychological insight.

Abstract

We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults ( N = 24), participants were randomized to an immediate ( N = 13) or delayed ( N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention ( p = .03, d = .43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks ( r = -.65, p = .002), 6 months ( r = -.47, p = .036), and 12 months ( r = -.54, p = .014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences ( r = .49, p = .027) and psychological insight ( r = .52, p = .040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks ( r = -.45, p = .030 for mystical; r = -.75, p < .001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks ( r = -.85, p < .001), 3 months ( r = -.52, p = .010), 6 months ( r = -.77, p < .001), and 12 months ( r = -.61, p = .001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529 . https://classic.clinicaltrials.gov/ct2/show/NCT03181529 .

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