Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder

Phase 3Not Yet RecruitingNCT06943573

Lakshmi N Yatham90 enrolled

Overview

This study is a 12-week (in addition to up to 30 days of screening) randomized, double-blind, placebo-controlled, parallel-group trial. The primary objective of this study is to assess the effectiveness, safety, and tolerability of single-dose psilocybin (25 mg)-assisted therapy in comparison to active placebo (1 mg micro-dose) psilocybin-assisted therapy in patients with bipolar II depression who have not responded to adequate trials with at least two first or second-line treatments for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). The active placebo is a substance that looks identical to the study medication but contains less therapeutic ingredients, and thus is less capable of producing the transformative and meaningful aspects of psychedelic experience compared to the 25 mg dose. Participants will have a total of 11 study visits over a period of up to 16 weeks, which includes 5 therapy sessions from trained study therapists.

Bipolar disorders (BD) are lifelong conditions characterized by recurrent episodes of depression and (hypo)mania. Statistics Canada data indicate over a million Canadians are affected by this illness. Bipolar II disorder is characterised by recurrent episodes of hypomania and depression and individuals with BD-II are symptomatic about 50% of the time despite treatment. The majority of this time is spent being depressed thus there is an urgent need to develop new treatments that are safe and effective. Psilocybin, a naturally occurring psychedelic compound found in mushrooms, has been noted to result in an increase in psychological well-being in healthy volunteers as well as have antidepressant effects when administered in conjunction with psychological support. Two recent open-label pilot trials of Psilocybin-Assisted Therapy (PAT) in treatment-resistant depression, including BD-II participants, demonstrated high response rates and excellent tolerability, thereby providing strong justification for the current study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 19 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. You are male or female aged 19 to 65 years inclusive. 2. You have a diagnosis of bipolar disorder type II, and are currently in a major depressive episode. 3. You are willing, for the entire duration of the study, to practice highly effective methods of contraception (e.g., contraceptive pills, intrauterine device or system, vasectomy and tubal ligation, or double-barrier methods of contraception) OR agree to completely abstain from heterosexual intercourse. Females who do not have childbearing potential are required to be postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) OR surgically sterile. 4. You have sufficient English language skills to understand, consent to, and comply with study requirements, study visits, and to return to the clinic for follow-up evaluations. 5. Your current medications have been at a stable dose for two weeks prior to the dosing visit. Exclusion Criteria: 1. You have a history of psychotic symptoms. 2. You have a history of seizures. 3. You have a current unstable or inadequately treated medical illness, especially cardiovascular illness, except for the current depression. 4. You recently (i.e., within the past 6 weeks) started taking treatment for your acute bipolar depressive episode. 5. You recently (i.e., within the past 8 weeks) began structured psychotherapy (e.g., cognitive-behavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy). 6. You have a history of nonresponse or intolerance to psilocybin. 7. You have, in the past 6 months, used any psychedelic drugs, including ketamine, LSD, or psilocybin-containing mushrooms. 8. You have a history of non-response to electroconvulsive therapy. 9. You are pregnant or lactating.

Locations (3)

Djavad Mowafaghian Centre for Brain Health

Vancouver, British Columbia, Canada

Department of Psychiatry, University of Ottawa, The Ottawa Hospital

Ottawa, Ontario, Canada

Department of Psychiatry, University of Toronto, University Health Network,

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Change in depressive symptoms

The Montgomery Asberg Depression Rating Scale (MADRS) will be used to measure change in depressive symptoms. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.

Time frame: Baseline to Week 3

Secondary Outcomes

Response Rates

Patients showing ≥50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) scores from Baseline. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.

Time frame: Week 3, Week 6, Week 12

Remission Rates

Defined as Montgomery Asberg Depression Rating Scale (MADRS) scores ≤ 10 and Young Mania Rating Scale (YMRS) scores ≤ 8. Scores for the MADRS range from 0 to 60, with lower scores reflecting better clinical outcomes. Scores for the YMRS range from 0 to 60, with lower scores reflecting better clinical outcomes.

Time frame: Endpoint

Treatment-emergent manic/hypomanic events

The Young Mania Rating Scale (YMRS) will be used to determine the presence of any treatment-emergent manic or hypomanic events from baseline to endpoint. Scores range from 0 to 60, and lower scores reflect better clinical outcome

Time frame: 12 weeks

Mean change in depressive symptoms

The Montgomery Asberg Depression Rating Scale (MADRS) will be used to measure mean change in depressive symptoms. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.

Time frame: Week 6 and 12

Subjective depressive symptoms

The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) will be used to measure change in subjective depressive symptoms from baseline to endpoint. Scores on the QIDS-SR range from 0 to 27; lower scores on the QIDS-SR reflect better clinical outcomes.

Time frame: 12 weeks

Symptoms of anhedonia

The Snaith-Hamilton Pleasure Scale (SHAPS) will be used to measure change in subjective symptoms of anhedonia from baseline to endpoint. Scores on the SHAPS range from 0 to 42; higher SHAPS scores indicate a reduced ability to experience pleasure and reduced capacity to feel pleasure.

Time frame: 12 weeks

Objective anxiety symptoms

The Hamilton Anxiety Rating Scale (HAM-A) will be used to measure change in objective anxiety symptoms from baseline to endpoint. Scores range from 0 to 56 and lower scores reflect better clinical outcomes.

Time frame: 12 weeks

Overall psychiatric status

The Clinical Global Impression - severity \& change scales will be used to measure change in global severity and global improvement in symptoms from baseline to endpoint. Scores range from 3 to 42, and higher scores reflect worsening in overall psychiatric status.

Time frame: 12 weeks

Psychotic symptoms

The Positive and Negative Syndrome Scale (PANSS) will be used to measure change in psychotic symptoms from baseline to endpoint. Scores range from 7 to 49, and lower scores reflect better clinical outcomes.

Time frame: 12 weeks

Subjective cognitive functioning

The Cognitive Complaints in Bipolar Disorder Risk Assessment (COBRA) scale will be used to measure change in subjective cognitive functioning from baseline to endpoint. COBRA scores range from 0 to 48, and lower scores reflect better outcomes.

Time frame: 12 weeks

Objective cognitive functioning

The Screen for Cognitive Impairment in Psychiatry (SCIP) will be used to measure change in objective cognitive functioning from baseline to endpoint. Higher scores reflect better outcomes.

Time frame: 12 weeks

Sleep quality

The Pittsburgh Sleep Quality Index (PSQI) will be used to measure changes in sleep quality and disturbance from baseline to endpoint. Lower scores reflect better sleep quality.

Time frame: 12 weeks

Quality of Life assessed by QoL.BD

The Brief Quality of Life in Bipolar Disorder (QoL.BD) will be used to measure change in quality of life from baseline to endpoint. Higher scores reflect higher quality of life.

Time frame: 12 weeks

Daily functioning

The Functioning Assessment Short Test (FAST) will be used to measure change in daily functioning from baseline to endpoint. Scores range from 0 to 72 with lower scores reflecting better daily functioning.

Time frame: 12 weeks

Suicidal thoughts and behaviours

The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to measure change in suicidal thoughts and behaviours from baseline to endpoint. Scores range from 0 to 37, and lower scores reflect better clinical outcomes.

Time frame: 12 weeks

MEQ30

Psychedelic experience will be measured by the MEQ30. Scores range from 30 to 150; higher scores reflect stronger (more profound) experiences.

Time frame: Dosing Visit (Day 0)

Clinician's perspective on the therapeutic relationship

The Therapeutic Relationship will be measured with the Scale to Assess the Therapeutic Relationship - Clinician version (STAR-C). Scores range from 0 to 48 respectively; higher scores reflect better therapeutic relationships.

Time frame: Baseline and Week 1

Patient's perspective on the therapeutic relationship

The Therapeutic Relationship will be measured with the Scale to Assess the Therapeutic Relationship - Patient version (STAR-P). Scores range from 0 to 48 respectively; higher scores reflect better therapeutic relationships.

Time frame: Baseline and Week 1

Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts