Psilocybin for Treatment-Resistant Depression

NCT05029466 | Completed Phase 2

• 1 other identifier: 253490
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if psilocybin, an investigational drug, is safe and well tolerated. Researchers also want to know if psilocybin can improve symptoms of depression. This study will see if psilocybin is safe and well tolerated by tracking changes in suicidal thoughts and behaviour, monitoring if any participants choose to stop participating in the study, and measuring any serious side effects, as well as how long they take to resolve. This study will also see if depression symptoms improve (or worsen) after psilocybin is administered. Additional information about participants' depressive symptoms and side effects will also be measured during the study.

Conditions

Treatment Resistant Depression

Keywords

Bipolar II Disorder; Major Depressive Disorder; Depressive Disorder, Treatment-Resistant; Mood Disorders; Mental Disorders; Psilocybin; Hallucinogen; Psychedelic; Antidepressant; Phase 2; Depression

Outcome Measures

Primary Outcomes (3)

• Feasibility of the study based on participant retention

  Participant drop-out rates will be calculated to determine the feasibility of psilocybin in adults with treatment-resistant depression.

  Up to 24 weeks

• Feasibility of the study based on suicidal ideation and behaviour scores

  Feasibility will be judged based on change in Columbia Suicide Severity Rating Scale (CSSRS) scores. The CSSRS evaluates suicidal ideation and behaviour. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

  Up to 24 weeks

• Feasibility of the study based on adverse events

  Feasibility will be judged based on the percentage of participants experiencing serious adverse events and the percentage of adverse events resolving within 48 hours of each dose administration.

  Up to 24 weeks

Secondary Outcomes (24)

• Montgomery-Åsberg Depression Rating Scale (MADRS) total score

  Up to 24 weeks

• Montgomery-Åsberg Depression Rating Scale (MADRS) response rate

  Up to 24 weeks

• Montgomery-Åsberg Depression Rating Scale (MADRS) remission rate

  Up to 24 weeks

• McIntyre and Rosenblat Rapid Response Scale (MARRRS)

  Up to 24 weeks

• Patient Health Questionnaire 9-item (PHQ-9)

  Up to 24 weeks

Study Arms (2)

Immediate treatment

EXPERIMENTAL

Participants will commence psilocybin treatment immediately upon study enrollment.

Drug: Psilocybin

Delayed treatment

EXPERIMENTAL

Participants will commence psilocybin treatment two weeks after study enrollment.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Participants will receive a single dose of psilocybin and be assessed weekly for six weeks and biweekly for 18 weeks. Participants who relapse may receive up to two repeated doses of psilocybin.

Delayed treatment; Immediate treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over the age of 18 years and under the age of 65;
• Diagnosed with major depressive disorder or bipolar II disorder by a healthcare provider;
• Experiencing a major depressive episode (MDE) without psychotic features as defined and operationalized in the DSM-5, where the duration of the current episode is at least 3 months;
• Have failed to respond to an adequate dose and duration of at least two guideline-concordant pharmacological treatments for the current MDE, as determined by the Massachusetts General Hospital-Antidepressant Treatment History Questionnaire; and
• Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.
• Individuals meeting one or more of the following DSM-5-defined criteria will be excluded:
• Current or past history of bipolar I disorder, schizophrenia, psychotic disorder, delusional disorder, paranoid personality disorder, or schizoaffective disorder, as assessed by a structured clinical interview (MINI) and International Personality Disorder Examination (IPDE);
• First degree history of schizophrenia or any psychotic disorders, including bipolar disorder with psychotic features;
• Currently experiencing symptoms of hypomania or mania as measured by the Young Mania Rating Scale (YMRS) total score \> 12;
• History of a hypomanic or manic episode in the past 3 months;
• History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 3 months;
• Lifetime history of substance use disorder with a hallucinogen;
• Lifetime history of substance-induced psychosis;
• Currently experiencing psychotic symptoms as part of an MDE (mood congruent/mood incongruent).
• Individuals meeting one or more of the following criteria will also be excluded:

Sponsors & Collaborators

• Brain and Cognition Discovery Foundation: lead
• Braxia Scientific Corp.: collaborator
• Usona Institute: collaborator

Study Sites (1)

Canadian Rapid Treatment Centre of Excellence (CRTCE)

Mississauga, Ontario, L5G 3H4, Canada

Location

Related Publications (1)

• Rosenblat JD, Meshkat S, Doyle Z, Kaczmarek E, Brudner RM, Kratiuk K, Mansur RB, Schulz-Quach C, Sethi R, Abate A, Ali S, Bawks J, Blainey MG, Brietzke E, Cronin V, Danilewitz J, Dhawan S, Di Fonzo A, Di Fonzo M, Drzadzewski P, Dunlop W, Fiszter H, Gomes FA, Grewal S, Leon-Carlyle M, McCallum M, Mofidi N, Offman H, Riva-Cambrin J, Schmidt J, Smolkin M, Quinn JM, Zumrova A, Marlborough M, McIntyre RS. Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin. Med. 2024 Mar 8;5(3):190-200.e5. doi: 10.1016/j.medj.2024.01.005. Epub 2024 Feb 14.

  PMID: 38359838 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Bipolar Disorder; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Joshua D Rosenblat, MD, MSc

  Canadian Rapid Treatment Centre of Excellence

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 31, 2021
• Study Start: November 19, 2021
• Primary Completion: July 22, 2023
• Study Completion: July 22, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)