Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Study Overview
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Brief Summary
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This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in 'magic mushrooms', with the SSRI (selective serotonin reuptake inhibitor) escitalopram for major depressive disorder (MDD).

Official Title
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Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Drug: Psilocybin + Placebo
* Drug: Psilocybin + Escitalopram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depressive disorder (DSM-IV) Depression of moderate to severe degree (17+ on the 21-item HAM-D). No MRI contraindications No SSRI contraindications Has a GP (general practitioner) or other mental healthcare professional who can confirm diagnosis 18-80 years of age Males and females Sufficiently competent with English language Key exclusion criteria: Current or previously diagnosed psychotic disorder Immediate family member with a diagnosed psychotic disorder Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure e.g. CLRC < 30 ml/min etc.) History of serious suicide attempts requiring hospitalisation. Significant history of mania (determined by study psychiatrist and medical records) Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin, e.g. borderline personality disorder Blood or needle phobia Positive pregnancy test at screening or during the study, women who are planning a pregnancy and/or women who are nursing/breastfeeding. Participants who do not agree to use an acceptable contraceptive method throughout their participation in study. Current drug or alcohol dependence No email access Use of contraindicated medication Patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 440ms for men and above 470ms for women)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin<br>Patients receive Psilocybin | Drug: Psilocybin + Placebo<br>* Multiple dosing days psilocybin vs 6 weeks of daily placebo<br>|
| Active Comparator: Escitalopram<br>Patients receive Escitalopram | Drug: Psilocybin + Escitalopram<br>* Multiple dosing days psilocybin vs 6 weeks of daily escitalopram<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional magnetic resonance imaging (fMRI) | Change in blood oxygen level dependent (BOLD) signal during fMRI in response to emotional faces during an emotional faces paradigm done inside the fMRI scanner. | Baseline measure vs 6 weeks post 1st psilocybin dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quick Inventory of Depressive Symptomatology (QIDS-SR16) | Change in QIDS-SR16 (self-rated measure of depressive symptoms). Scale is composed of 16 items that correlate with the 9 DSM-IV symptom criteria for depression. Each response is graded 0-4 (none-severe symptoms). Questions 1-4 concern sleep disturbances, Question 5 addresses sad mood, Questions 6-9 appetite/weight, Question 10 concentration, Question 11 self-criticism, Question 12 suicidal ideation, Question 13 interest, Q14 energy/fatigue and Questions 15-16 psychomotor agitation/retardation. All questions that address the same topic are grouped and only the highest score from each group is summed up together with the other questions in order to produce a total score. Scores can range from 0-27 and depression severity is graded based on the total score in the following way: 1-5 = No depression 6-10 = Mild depression 11-15 = Moderate depression 16-20 = Severe depression 21-27 = Very severe depression | Baseline vs 6 weeks post 1st psilocybin dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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escitalopram, ssri, depression, mdd, major depression, major depressive disorder, unipolar depression, psilocybin, psychedelics, psychedelic