Understanding Music and Mindfulness Preferences in Psilocybin-Assisted Psychotherapy

Depression is one of the top causes of disability worldwide. Psilocybin-assisted psychotherapy (PAP) is an emerging treatment for Treatment-Resistant Depression (TRD) that pairs one or two doses of psilocybin, a serotonergic psychedelic, with a brief course of psychotherapy. While multiple studies of PAP have found safe, rapid, and lasting antidepressant effects, much remains unknown about how to optimize this promising intervention's psychotherapy component. This pilot study aims to explore a novel strategy for improving the efficacy and tolerability of PAP: individually-tailoring its psychotherapy based on patient preferences for two important nonpharmacological treatment elements: music and mindfulness. These core treatment components were selected based on their ubiquitousness in psilocybin studies and their potential for significant patient preference effects. The investigators will conduct a patient-preference randomized clinical trial where 16 patients with TRD will receive two doses of psilocybin (PEX010, Filament Health, 25mg). For each patient, one psilocybin dose will be administered with music-centered psychological support and the other with mindfulness-centered psychological support. In the first 4-week phase, patients will be asked to rate their preferences for these different psychotherapeutic approaches. Patients will then be 50:50 randomized to first receive either their preferred or their non-preferred treatment approach. In a second 4-week crossover phase, patients will receive the other treatment approach. All patients will thus undergo both music-centered and mindfulness-centered PAP interventions, but in an order dictated by their preferences and randomization. Each treatment phase entails pre-treatment and post-treatment psychotherapy following standard protocols. Similar patient-preference clinical trial designs have shown that preferences can significantly influence the efficacy and tolerability of existing psychiatric treatments. The primary aim of this pilot trial is to examine this design's feasibility for exploring such preference effects in PAP, which the investigators hypothesize will be substantial. As secondary aims, the trial will generate preliminary estimates about the magnitude of preference effects, compare the music- and mindfulness-centered approaches, and yield qualitative data about the diverse sociocultural factors that influence patient preferences, including with a modified Cultural Formulation Interview administered at baseline. An additional exploratory aim is to examine novel physiological measures of therapeutic alliance, a crucial factor in psychiatric care. Depression affects millions of Canadians and new treatments are sorely needed. This line of research seeks to produce systematic approaches to tailoring the psychotherapy of PAP for TRD. Its ultimate goal is to improve this promising intervention's efficacy, safety, and applicability to diverse populations.