Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Phase 2

Completed

• Conditions: Depressive Disorder, Major
• Interventions: Drug: Psilocybin + Escitalopram; Drug: Psilocybin + Placebo

• Registration Number: NCT03429075
• Lead Sponsor: Imperial College London

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 selective serotonin reuptake inhibitor (SSRI) escitalopram for major depressive disorder (MDD).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-12-06
• Study First Submitted QC: 2018-02-05
• Study First Posted: 2018-02-12
• Study Start: 2019-01-07
• Primary Completion: 2020-04-17
• Study Completion: 2020-10-17
• Results First Submitted: 2021-08-05
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-02
• Last Update Submitted: 2024-08-02
• Results First Posted: 2024-10-24
• Last Update Posted: 2024-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

1. Major depressive disorder (DSM-IV)
2. Depression of moderate to severe degree (17+ on the 17-item Hamilton Depression Scale (HAM-D)).
3. No Magnetic Resonance Imaging (MRI) contraindications
4. No SSRI contraindications
5. Has a general practitioner (GP) or other mental healthcare professional who can confirm diagnosis
6. 18-80 years of age
7. Males and females
8. Sufficiently competent with English language

Key exclusion criteria:

1. Current or previously diagnosed psychotic disorder
2. Immediate family member with a diagnosed psychotic disorder
3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure e.g. creatine clearance:renal clearance (CLRC) < 30 ml/min etc.)
4. History of serious suicide attempts requiring hospitalisation.
5. Significant history of mania (determined by study psychiatrist and medical records)
6. Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin, e.g. borderline personality disorder
7. Blood or needle phobia
8. Positive pregnancy test at screening or during the study, women who are planning a pregnancy and/or women who are nursing/breastfeeding.
9. Participants who do not agree to use an acceptable contraceptive method throughout their participation in study.
10. Current drug or alcohol dependence
11. No email access
12. Use of contraindicated medication
13. 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)

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Escitalopram	Psilocybin + Escitalopram	Patients receive Escitalopram
Psilocybin	Psilocybin + Placebo	Patients receive Psilocybin

Primary Outcome Measures

Name	Time	Method
Percentage Change of the BOLD Signal	Baseline measure vs 6 weeks post 1st psilocybin dosing	Patients were tested with functional magnetic resonance imaging (fMRI) to measure brain brain responses to emotional faces before and after the treatment. The 2 values of BOLD signal (before and after exposure to emotional faces) were used to estimate a percentage value per patient and then these were used to estimated a group percentage change.
Change in QIDS-16: Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-16)	Baseline vs 6 weeks post 1st psilocybin dosing	Change in QIDS-16 (self-rated measure of depressive symptoms). Scale is composed of 16 items that correlate with the 9 Diagnostic Statistical Manual (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; Lower score =better outcome (less depression)

Secondary Outcome Measures

Name	Time	Method
Change in Hamilton Depression Scale (HAMD-17)	Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose	HAMD-17: clinician rated Hamilton Depression Scale of depression severity. Range of scores: 0-52: where 0-7 is normal, 8-16 is mild, 17-23 is moderate, \>23 is severe.; A threshold score of 17 is the entry: a score of 17 or higher indicated moderate-severe depression and was a requirement for entry into this trial at the screening point. This baseline does not refer to the screening point, it refers to the HAMD conducted 7-10 days before psilocybin dosing.; A higher decrease in the HAMD (larger negative change score) is a better outcome.
Change in Beck Depression Inventory (BDI-IA)	Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose	BDI-IA: patient-rated Beck Depression Inventory, depressive symptomatology scale. Higher score = worse depression. The total score range is 0-63: where 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe; Higher negative score = greater decrease in depression scores 6 weeks after each treatment arm = better outcome.
Change in MADRS	Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose	MADRS - Montgomery-Asberg Depression Rating Scale, clinician-rated measure of depression. This scale is clinician-rated and consists of 10 items; each item is rated on a 0-6 scale, resulting in a maximum total score of 60 points, with higher scores indicative of greater depressive symptomology.36 The MADRS scoring instructions indicate that a total score ranging from 0 to 6 indicates that the patient is in the normal range (no depression), a score ranging from 7 to 19 indicates "mild depression," 20 to 34 indicates "moderate depression," a score of 35 and greater indicates "severe depression," and a total score of 60 or greater indicates "very severe depression."; A higher decrease in the MADRS (larger negative change score) is a better outcome.
Number of Patients Who "Responded": Quick Inventory of Depressive Symptomatology (QIDS-16) Response at 6 Weeks	Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose	Number of patients who "responded" on the QIDS-16 scale (Quick Inventory of Depressive Symptomatology, self-rated). "Response" is defined by a decrease in QIDS score of 50% from baseline.; Higher number of patients who responded = better outcome for treatment arm.
Number of Patients Who "Remitted": QIDS-16 Remission Rate	Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose	Number of patients who "remitted" on the QIDS-16 scale (Quick Inventory of Depressive Symptomatology, self-rated). "Remission" is defined by having a QIDS score below 5 at the 6 week point = no depression.; Higher remission rate = better outcome (less depressed patients after treatment)

Trial Locations

Locations (1)

Imperial College Hammersmith campus; 🇬🇧 London, United Kingdom