Psilocybin Therapy for Depression in Bipolar II Disorder

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder.

Detailed Description
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The primary goal of this study is to examine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder (BD II). Fourteen participants, ages 18 to 70 with clinically diagnosed BD II with active depression, in active outpatient mental health treatment, and who meet all other inclusion and exclusion criteria at screening will be enrolled. After baseline assessments, participants will engage in preparatory visits with trained facilitators, followed by an initial drug administration of oral psilocybin,supervised by the facilitators and a clinician who will conduct safety monitoring throughout. Participants will complete assessment and integration sessions with the facilitators subsequently in order to help process the experience. Participants who tolerated the first dosage may be asked to complete a second psilocybin dosing session, involving the same preparation, procedures, integration, and supervision as the first. Primary outcome measures will assess safety, tolerability, and feasibility of study procedures. Efficacy will be measured by change in depression as measured by the MADRS three weeks after the final psilocybin administration. Exploratory outcome measures will assess changes in sleep, quality of life, and therapeutic engagement.

Official Title
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An Open-Label Pilot Study Examining the Feasibility, Safety, and Effectiveness of Psilocybin Therapy for Depression in Bipolar II Disorder

Conditions
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Bipolar II Disorder

Intervention / Treatment
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* Drug: Psilocybin therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 70 Comfortable speaking and writing in English Diagnosis of Bipolar Disorder II with current depression Have a care partner/support person available throughout the study Able to attend all in-person visits at UCSF as well as virtual visits Having tried at least one previous medication trials for their bipolar disorder, each lasting at 6 weeks or more. Have an established mental health care provider who is seen at least once a month Exclusion Criteria: Current or previous diagnosis of Bipolar I Disorder History of schizophrenia spectrum or psychotic disorder Use of psychedelics within the past 12 months, including MDMA and Ketamine Current diagnosis of cancer Seizures that continue to the present Fear of blood or needles Regular use of medications that may have problematic interactions with psilocybin, including but not limited to antidepressants (Bupropion allowed), serotonin antagonists, some antipsychotics, dopamine agonists/antagonists, stimulants, opioids, and Lithium. A health condition that makes this study unsafe or unfeasible, determined by study physicians

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single-arm, pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin therapy<br>Participants will receive one or two doses of psilocybin in a monitored setting approximately three weeks apart, with preparation sessions before and integration sessions after. | Drug: Psilocybin therapy<br>* - Psilocybin administration session 10mg-25mg delivered orally with psychological support and monitoring<br>* Other names: 4-phosphoryloxy-N,N-dimethyltryptamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of psilocybin therapy for depression in BD II | -Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs) | Baseline to 3 months following last drug dose | 
| Recruitment rate | -Measured as a percentage of participants who were contacted for pre-screening and consented. | Baseline to 3 months following last drug dose | 
| Retention rate | -Measured as a percentage of participants who began and completed treatment. | Baseline to 3 months following last drug dose | 
| Clinician-reported effects of psilocybin therapy on depressive symptoms in people with Bipolar II | Montgomery-Asberg Depression Rating Scale (MADRS) Each item is scored on a on a scale of 0-6 with a total score of 0-60 Higher scores correspond to worse outcomes | Baseline to 3 weeks following last drug dose | 
| Treatment Satisfaction of study procedures | Measured by the treatment satisfaction questionnaire 5-item scale, plus three free response questions Higher scores representing better treatment satisfaction | Baseline to 3 months following last drug dose | 
| Self-reported effects of psilocybin therapy on manic and/or psychotic symptoms in people with Bipolar II | Altman Self-Rating Mania Scale(ASRM-14) Each item rated on a 0 to 4 scale, with a total score of 0 to 56 Higher scores indicating greater severity of manic symptoms, with items that also measure psychosis | Baseline to 11 days following each drug dose | 
| Clinician-reported effects of psilocybin therapy on mania symptoms in people with Bipolar II | Young Mania Scale(YMS) 7 items are rated on a 0 to 4 scale and 4 items are rated on a 0 to 8 scale. The total score ranges from 0-60 Higher scores indicating greater severity of manic symptoms. | Baseline to 3 months following each drug dose | 
| Clinician-reported effects of psilocybin therapy on suicidality symptoms in people with Bipolar II | Columbia-Suicide Severity Rating Scale (C-SSRS) Characterizes suicidal ideation in three separate categories with a total score range from 0-25 Higher scores indicate greater severity | Baseline to 3 months following last drug dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported effects of psilocybin therapy on depressive symptoms symptoms in people with Bipolar II (exploratory) | Quick Inventory of Depressive Symptomatology (QIDS-SR) Each item is scored on a on a scale of 0-3, with a total score of 0-27 Higher scores correspond to worse outcomes | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on anxiety symptoms in people with Bipolar II (exploratory) | Generalized Anxiety Disorder 7-item scale (GAD-7) Each item is rated on a scale from 0-3, with a total score of 0-21 Higher scores correspond to worse outcomes | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on sleep quality in people with Bipolar II (exploratory) | Insomnia Severity Index (ISI) Each item is scored on a scale of 0-4 with a total score range of 0-28 Higher scores indicate greater severity in sleep disturbance | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on quality of life in people with Bipolar II (exploratory) | Quality of Life in Bipolar Disorder Questionnaire (QoL-BD) Each item is scored on a scale of 1-5 with a total score range of 48-240 Higher scores indicate greater quality of life | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on borderline personality disorder symptoms in people with Bipolar II (exploratory) | Zanarini Rating Scale (ZRS) Each item is scored on a scale of 0-4 with a total score range of 0-30 Higher scores indicate greater severity in symptoms | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on adult attachment in people with Bipolar II (exploratory) | Experiences in Close Relationships-Modified 16-Item Scale (ECR-M16) Each item is scored on a scale of 1-7 with a total score range of 8-126 Lower scores on each dimension of attachment anxiety and avoidance represent greater levels of attachment security | Baseline to 3 months following last drug dose | 
| Effects of psilocybin therapy on participant-reported recovery in people with Bipolar II (exploratory) | Bipolar Recovery Questionnaire (BRQ) 36 items (visual analog scales) Higher total scores indicate a higher degree | Baseline to 3 months following last drug dose | 
| Subjective effects of psilocybin therapy in people with Bipolar II | 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) 94 items (visual analog scales) broken down into subcategories to quantify the acute subjective effects of psilocybin directly following each psilocybin administration session | Baseline to 3 months following last drug dose | 
| Subjective effects of psilocybin therapy in people with Bipolar II | Study specific Transformational Experiences Questionnaire (TEQ) Meant to quantify subjective effects of psilocybin on 1-7 scale | 3 weeks following last drug dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bipolar, Depression, Psilocybin, Psychedelic, Psilocybin Therapy, Bipolar II, Safety