Acceptability & Safety of Two Sequential Doses of Psilocybin in Bipolar Disorder II Depression and Suicidality

Обзор

The purpose of the study is to assess the safety and acceptability of up to two sequential administrations of 25 mg psilocybin with additional therapeutic support in decreasing suicidality in patients with Bipolar Disorder (BD II) depression.

Подробное описание

This study aims to determine whether psilocybin paired with psychotherapy is a safe, feasible, and acceptable treatment for Bipolar II (BD II) depression, specifically, individuals experiencing suicidal ideation (without having an active plan or intention to act). The design is a non-randomized clinical trial, where patients will receive up to 2 doses of 25mg psilocybin in the context of psychological support informed by mindfulness-based CBT and typical elements of psychedelic treatments (e.g., preparation, intention setting, integration). The investigators will measure suicidality, depression, and acute experiences using validated questionnaires at multiple time points in the study. If this study shows psilocybin to be a feasible, acceptable, and safe treatment option, this would have huge implications for improving outcomes because highly effective treatment for suicidality in patients with Bipolar Disorder is still lacking.

Вмешательства

• Препарат Psilocybin
  Two sequential administrations of 25 mg psilocybin, 4 weeks apart.
• Поведенческое Therapeutic Support
  Five preparatory in-person psychotherapy sessions will be offered before the first administration session during weeks 1, 2, 3, 4, and 5. The optional second administration session will be preceded by a shorter 60 min preparatory session the day before. Each administration session will be followed by 3 integration sessions and will adopt a Mindfulness-based CBT approach (M-CBT), in which a therapist will help the participant to process their experience and how to translate this into actual chan

Первичные конечные точки

• Feasibility as Assessed by Number of Participants who Complete the Trial (Overall Retention) [Срок оценки: from baseline to 3 weeks after first administration session]
• Feasibility as Assessed by Number of Therapy Sessions Attended [Срок оценки: from baseline to 3 weeks after first administration session]
• Feasibility as Assessed by Number of Assessments Completed [Срок оценки: from baseline to 3 weeks after first administration session]
• Acceptability of Two Dosing Sessions as Assessed by Number of Participants who Choose to Participate in a Second Administration Session [Срок оценки: 11 weeks after first administration session]
• Acceptability as Assessed by Number of Therapy Sessions Attended [Срок оценки: from baseline to 11 weeks after first administration session]
• Acceptability as Assessed by Number of Assessments Completed [Срок оценки: from baseline to 11 weeks after first administration session]
• Score on the Thwarted Belongingness (TB) Items of the Interpersonal Needs Questionnaire (INQ-15) [Срок оценки: baseline, 3 weeks after first administration session]
• Score on the Perceived Burdensomeness (PB) Items of the Interpersonal Needs Questionnaire (INQ-15) [Срок оценки: baseline, 3 weeks after first administration session]
• Score on the Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: baseline, 3 weeks after first administration session]

Вторичные конечные точки (5)

• Score on the Montgomery-Åsberg Depression Rating Scale (MADRS) [Срок оценки: baseline, 3 weeks after first administration session]
• Score on the Quick Inventory of Depressive Symptomatology (QIDS-SR16) [Срок оценки: baseline, 3 weeks after first administration session]
• Score on the Young Mania Rating Scale (YMRS) [Срок оценки: baseline, 3 weeks after first administration session]
• Psychiatric Symptoms as Assessed by Score on the Brief Psychiatric Rating Scale (positive symptom subscale) (BPRS+) [Срок оценки: baseline, 3 weeks after first administration session]
• Score on the Altman Self-Rating Mania Scale (ASRM) [Срок оценки: baseline, 3 weeks after first administration session]

Критерии участия

Критерии включения

• Must have completed written informed consent
• Must be at 25 years of age or older at screening (but below age of 70)
• Confirmed Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of BD-II using clinical records and Diagnostic Interview for Anxiety, Mood, and Obsessive-compulsive disorder (OCD) and Related Neuropsychiatric Disorders (DIAMOND)
• Must meet criteria for suicidality according to the INQ cutoff scores: A score of at least 12 on the Perceived Burden (PB) subscale and at least a score of 36 on the Thwarted Belongingness (TB) subscale indicating substantial risk for passive suicidal ideation
• Must meet criteria for depression according to the MADRS cutoff scores: A score of 7-34 indicating mild to moderate depression
• Must pass medical examination (physical exam, personal/family medical history, including consultation with current medical provider, ECG, about 4 tablespoons blood draw, psychiatric/psychological assessments, urine drug test)
• Willingness to taper down mood stabilizers and other relevant medications (including but not limited to: antidepressants, antipsychotics, lithium, benzodiazepines, Monoamine oxidase inhibitors (MAOIs), Selective serotonin reuptake inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs), A serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs), Tricyclic antidepressants (TCAs), stimulants, cannabis, and other medications, supplements or therapeutics that affect serotonergic function) for the duration of the study before and during administration days (starting 5 weeks before administration), and be off medication for at least 2 weeks prior to administration
• Willingness to stop allowed medication at least 24 h prior to administration of psilocybin as advised by study physician (e.g., benzodiazepines)
• Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits

Критерии исключения

• Participants who do not read/speak English
• Active suicidal ideation with at least some intent and/or plan (i.e., a current score of 4 or 5 on the C-SSRS)
• History of medically significant suicide attempt in the last 6 months
• Current or past history of Bipolar I disorder, psychotic symptoms or psychotic disorder, (including but not limited to schizophrenia, delusional disorder, schizoaffective disorder) clinically relevant personality disorder (such as borderline, antisocial, narcissistic or paranoid personality disorder), or any serious psychiatric comorbidity considered negatively impacting participation or safety (e.g., PTSD or severe substance use or alcohol disorder) assessed by medical history and/or a structured clinical interview
• Have a first or second degree relative with Bipolar I disorder or a psychotic disorder
• Currently experiencing a hypomanic or mixed-symptom episode
• Have a psychiatric or other condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• Any indication of a Personality Disorder (PD) such as but not limited to Borderline, Narcissistic, Antisocial, Paranoid, or Schizotypal PD based on Structured Clinical Interview for DSM-5 for PD and/or clinical judgment

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• The University of Texas Health Science Center at Houston — Houston

Публикации

• Aaronson ST, van der Vaart A, Miller T, LaPratt J, Swartz K, Shoultz A, Lauterbach M, Sackeim HA, Suppes T. Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial. JAMA Psychiatry. 2024 Jun 1;81(6):555-562. doi: 10.1001/jamapsychiatry.2023.4685. PMID 38055270
• Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry PMID 36001306
• Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8. PMID 29119217
• Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285. PMID 33146667
• Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Kel PMID 36322843
• Meyer TD, Vale LN, Ibrahim M, Olmos C, Quevedo J, Soares JC. Acceptability and safety of two sequential doses of psilocybin in bipolar II depression: protocol for an open-label single-arm feasibility study. BMJ Open. 2026 Jul 13;16(7):e118471. doi: 10.1136/bmjopen-2026-118471. PMID 42442821

Идентификаторы

NCT: NCT06706232 · HSC-MS-23-0905

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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