The goal of this pilot clinical trial is to learn whether it is feasible to individually tailor psilocybin-assisted psychotherapy (PAP) for people with treatment-resistant depression (TRD) based on their personal preferences. The study also aims to explore whether two different psychotherapy styles, music-centered and mindfulness-centered, influence how people respond to psilocybin treatment. The main questions it aims to answer are: * Is it feasible to conduct a patient-preference randomized trial of psilocybin-assisted psychotherapy? * Does receiving a preferred psychotherapy style improve treatment experiences or outcomes? * How do music-centered and mindfulness-centered PAP approaches compare in their effects on improving mood and well-being? Researchers will compare music-centered PAP to mindfulness-centered PAP to see if aligning psychotherapy with individual preferences is a practical and potentially beneficial approach for improving treatment efficacy and tolerability. Participants will: * Be adults with treatment-resistant depression * Receive two 25 mg psilocybin (PEX010, Filament Health) sessions, spaced four weeks apart * Experience one session with music-centered psychotherapy and one with mindfulness-centered psychotherapy * Before treatment, rate their preference for the two psychotherapy approaches * Be randomly assigned to receive their preferred or non-preferred approach first, followed by the other * Complete preparation and integration sessions before and after each psilocybin session This feasibility trial will also collect information on participants' cultural and personal factors influencing psychotherapy preferences using a modified Cultural Formulation Interview, and explore physiological measures of therapeutic alliance, an important factor in psychotherapy outcomes.
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Enrollment Feasibility
Timeframe: From screening through enrollment
Overall Trial Completion Feasibility
Timeframe: From enrollment through the end of active treatment (Week 10)
Trial Completion by Preference Assignment
Timeframe: From enrollment through the end of active treatment (Week 10)
Distribution of Treatment Preferences
Timeframe: Baseline
Ease of Delivering Treatment Approaches as Assessed by the NASA-TLX
Timeframe: End of each psilocybin treatment session (Week 3, Week 9)
Theoretical Framework of Acceptability (TFA)
Timeframe: Baseline, Weeks 3 and 9 (treatment sessions), Week 11 (follow-up)