Psilodep-RCT: Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Sponsor

Imperial College London (Other)

Overall Status

Unknown status

CT.gov ID

NCT03429075

Collaborator

Alexander Mosely Charitable Trust (Other)

Enrollment

Location

Arms

20.8

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: Psilocybin + Placebo Drug: Psilocybin + Escitalopram	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Actual Study Start Date :

Jan 7, 2019

Actual Primary Completion Date :

Apr 17, 2020

Anticipated Study Completion Date :

Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Psilocybin Patients receive Psilocybin	Drug: Psilocybin + Placebo Multiple dosing days psilocybin vs 6 weeks of daily placebo
Active Comparator: Escitalopram Patients receive Escitalopram	Drug: Psilocybin + Escitalopram Multiple dosing days psilocybin vs 6 weeks of daily escitalopram

Arm

Intervention/Treatment

Experimental: Psilocybin

Patients receive Psilocybin

Drug: Psilocybin + Placebo

Multiple dosing days psilocybin vs 6 weeks of daily placebo

Active Comparator: Escitalopram

Patients receive Escitalopram

Drug: Psilocybin + Escitalopram

Multiple dosing days psilocybin vs 6 weeks of daily escitalopram

Outcome Measures

Primary Outcome Measures

functional magnetic resonance imaging (fMRI) [Baseline measure vs 6 weeks post 1st psilocybin dosing]
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.

Secondary Outcome Measures

Quick Inventory of Depressive Symptomatology (QIDS-SR16) [Baseline vs 6 weeks post 1st psilocybin dosing]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)