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

In a small randomized trial of psilocybin-assisted therapy for adults with major depressive disorder, the therapeutic alliance between participants and facilitators strengthened from the final preparation session to one week after the intervention. A stronger alliance before the psilocybin sessions predicted lower depression scores at 4 weeks, 6 months, and 12 months afterward. Stronger alliance also correlated with more intense mystical experiences and psychological insight during the drug sessions, which in turn predicted better depression outcomes. The findings suggest the therapeutic relationship is important for treatment success.

Study at a glance

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 .