Toward Patient-Tailored Care for Treatment-Resistant Depression: A Pilot Patient-Preference Clinical Trial of Music and Mindfulness in Psilocybin-Assisted Psychotherapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Enrollment Feasibility
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 21 years of age at screening.
- •Diagnosis of unipolar Major Depressive Disorder (MDD) according to diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), confirmed by a study psychiatrist using the Mini International Neuropsychiatric Interview (MINI) version 7.0.
- •Failure to achieve remission from at least two trials of evidence-based oral antidepressants, in the current episode, of adequate dose and duration.
- •Moderate to severe symptoms according to the clinician-administered Montgomery-Åsberg Depression Rating Scale (MADRS): total score ≥ 25 on screening.
- •Active follow-up in psychiatry.
- •Able and willing to give informed consent to participate in the study, and for the study clinicians to communicate with their psychiatrist throughout the intervention phase of the study.
- •Available and willing to comply with all study assessments.
- •Stable psychotropic medications for at least eight weeks at the time of enrollment.
- •Able to read and understand French and/or English.
- •Has at least one identified support person, including a friend or family member, who agrees to accompany patient home (or to an otherwise safe destination) following the psilocybin treatment sessions.
排除标准
- •Deemed to be greater than low risk of suicide on psychiatric interview.
- •Currently or previously diagnosed with any of the following, according to available information and psychiatric interview: major depression with psychotic features, schizophrenia spectrum or other psychotic disorders, and/or bipolar affective disorder I or related disorders.
- •Current or past diagnosis of personality disorder deemed to pose a significant risk for safety and/or trial compliance.
- •Family history (first-degree relative) of psychosis.
- •Current or recent (< six months) substance use disorder, except for tobacco use disorder.
- •Deemed to be greater than low risk of future substance use disorder.
- •Currently receiving and deemed to be unsuitable, on psychiatric interview, to discontinue medications with significant serotonin 2A antagonism (e.g., trazodone) or known potential for serious interactions with psilocybin including serotonin syndrome (e.g., monoamine oxidase inhibitors), seizures (e.g., lithium), or which may affect psilocybin pharmacokinetics (e.g. UDG modulators, aldehyde dehydrogenase inhibitors).
- •Unwilling or unable to maintain current psychotropic medications throughout the treatment phase of the trial.
- •Currently undergoing psychotherapy that will not remain stable for the duration of the study or was initiated within 21 days of baseline.
- •Prior use of serotonergic psychedelics in the past year and/or more than five life-time uses.
- •Use of any serotonergic psychedelic or ketamine, or any other illicit substance during the active treatment period of the trial.
- •Medical contraindications:
- •Current or past history of seizure disorder with the exception of infantile febrile seizures.
- •Significant cardiovascular disease including uncontrolled blood pressure (> 140/90mmHg), clinically significant arrhythmia, heart failure, coronary artery disease, history of ischemic or hemorrhagic stroke, or history of myocardial infarction.
- •Abnormal and clinically significant results on the physical examination, laboratory investigations, or ECG at screening.
- •Any other clinically significant illness deemed to pose significant health risks for participation in the study.
- •Pregnant or lactating.
- •For women of child-bearing potential, defined as all women physiologically capable of becoming pregnant: unwilling to utilize highly effective contraceptive during the 10-week active intervention (e.g., oral contraceptive). Acceptable forms of highly effective contraception methods include: a. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b. Male/female sterilization defined as: 1) Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed and documented by follow up hormone level assessment; 2) Male sterilization of the sole partner (at least 6 months prior to screening) of a female patient on the study. c. A combination of any two of the following (i+ii or i+iii or ii+iii):
- •i) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository ii) Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception iii) Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- •Men unwilling to not attempt to father a child or not donate sperm, while participating the active treatment period of this study.
研究组 & 干预措施
Non-preferred treatment
干预措施: Psilocybin 25mg (Drug)
Preferred treatment
干预措施: Music-centered psilocybin-assisted therapy (Other)
Preferred treatment
干预措施: Mindfulness-centered psilocybin-assisted therapy (Other)
Non-preferred treatment
干预措施: Music-centered psilocybin-assisted therapy (Other)
Non-preferred treatment
干预措施: Mindfulness-centered psilocybin-assisted therapy (Other)
Preferred treatment
干预措施: Psilocybin 25mg (Drug)
结局指标
主要结局
Enrollment Feasibility
时间窗: From screening through enrollment
The proportion of participants screened as eligible who enroll in the trial.
Overall Trial Completion Feasibility
时间窗: From enrollment through the end of active treatment (Week 10)
The proportion of enrolled participants who complete the trial, defined as attending ≥ 90% of required study visits.
Trial Completion by Preference Assignment
时间窗: From enrollment through the end of active treatment (Week 10)
The proportion of participants in the preferred and non-preferred treatment groups who complete ≥ 90% of study visits.
Distribution of Treatment Preferences
时间窗: Baseline
The proportion of participants who choose the music-centered versus the mindfulness-centered approach as their preferred treatment at baseline.
Ease of Delivering Treatment Approaches as Assessed by the NASA-TLX
时间窗: End of each psilocybin treatment session (Week 3, Week 9)
The ease of delivering the music-centered versus the mindfulness-centered as assessed by therapists' reported levels of effort with each intervention measured with the NASA Task Load Index (NASA-TLX). The NASA Task Load Index (NASA-TLX) is a self-reported measure assessing perceived workload and cognitive effort during a task that will be completed by the therapists. It evaluates six dimensions: Mental Demand, Physical Demand, Temporal Demand, Performance, Effort, and Frustration. Each dimension is rated using a continuous 0-100 visual analog scale, with anchors ranging from very low (0) to very high (100) (for Performance, 0 = poor to 100 = excellent). Higher scores reflect greater perceived workload, except for Performance, where higher scores indicate better perceived performance. Scores will be compared by preference group (preferred vs. non-preferred) and therapeutic approaches (music-centered vs. mindfulness-centered).
Theoretical Framework of Acceptability (TFA)
时间窗: Baseline, Weeks 3 and 9 (treatment sessions), Week 11 (follow-up)
Acceptability of each therapeutic approach as measured by the Theoretical Framework of Acceptability (TFA) questionnaire for music-centered and mindfulness-centered interventions. Items cover comfort with the intervention, effort required, ethical or moral concerns, perceived effectiveness, clarity of intervention rationale, confidence in performing required activities, potential interference with other priorities, and overall acceptability. Each item is rated on a 5-point Likert scale (1 = lowest to 5 = highest). Total scores are calculated by summing all item responses, with possible scores ranging from 8 to 40. Higher scores indicate greater acceptability of the intervention.
次要结局
- Rate of Adverse Events in Music- versus Mindfulness-centered Interventions(Baseline, Week 5 (primary endpoint), Week 11 (follow-up))
- Rate of Adverse Events in Preferred vs. Non-Preferred Interventions(Baseline, Week 5 (primary endpoint), Week 11 (follow-up))
- Rate of Participant Drop-Outs in Preferred vs. Non-Preferred Interventions(Baseline, Week 5 (primary endpoint), Week 11 (follow-up))
- Rate of Participant Drop-Outs in Music- versus Mindfulness-centered Interventions(Baseline, Week 5 (primary endpoint), Week 11 (follow-up))
- Change From Baseline in MADRS Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in BDI-II Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in GAD-7 Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in the 5-level EQ-5D version (EQ-5D-5L) Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in Work and Social Adjustment Scale (WSAS) Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in Gratitude Questionnaire-Six Item Form (GQ-6) Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in Multidimensional Psychological Flexibility Inventory (MPFI-24) Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Change From Baseline in Watts Connectedness Scale (WCS) Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Psychedelic Music Questionnaire Short-Form (PMQ-SF)(End of each psilocybin treatment session (Week 3, Week 9))
- Change From Baseline in Pearlin Mastery Scale Total Score to Key Endpoint(Baseline, Week 5 (primary endpoint))
- Semi-structured Qualitative Interviews(Baseline, Week 11 (follow-up))
- Challenging Experience Questionnaire Brief (CEQ-7)(End of each psilocybin treatment session (Week 3, Week 9))
- Acceptance/Avoidance-Promoting Experiences Questionnaire (APEQ-SF)(End of each psilocybin treatment session (Week 3, Week 9))
- Imprinting (Self-constructed)(End of each psilocybin treatment session (Week 3, Week 9))
- Mystical Experience Questionnaire Brief (MEQ-4)(End of each psilocybin treatment session (Week 3, Week 9))
- Awe Experience Scale - Short Form (AWE-SF)(End of each psilocybin treatment session (Week 3, Week 9))
- Modified Psychedelic Communitas Scale(End of each psilocybin treatment session (Week 3, Week 9))
研究者
Kyle Greenway
Psychiatrist and Investigator
Sir Mortimer B. Davis - Jewish General Hospital