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

• ClinicalTrials.gov Identifier: NCT03429075
• Recruitment Status: Unknown
• First Posted: February 12, 2018
• Last Update Posted: July 31, 2020
• Sponsor: Imperial College London
• Collaborator: Alexander Mosely Charitable Trust
• Information provided by (Responsible Party): Imperial College London

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 (Clinical Trial)
• 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: January 7, 2019
• Actual Primary Completion Date: April 17, 2020
• Estimated Study Completion Date: October 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

Outcome Measures

Primary Outcome Measures :

1. functional magnetic resonance imaging (fMRI) [ Time Frame: 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 :

1. Quick Inventory of Depressive Symptomatology (QIDS-SR16) [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Major depressive disorder (DSM-IV)
2. Depression of moderate to severe degree (17+ on the 21-item HAM-D).
3. No MRI contraindications
4. No SSRI contraindications
5. Has a GP (general practitioner) 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. 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)

Contacts and Locations

Locations

United Kingdom

Imperial College Hammersmith campus

London, United Kingdom, W12 0NN

Sponsors and Collaborators

Imperial College London

Alexander Mosely Charitable Trust

Investigators

• Principal Investigator: David J Nutt, Medicine; Imperial College London

More Information

Publications:

Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Murphy R, Kettner H, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker-Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris R. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression. Front Pharmacol. 2022 Mar 31;12:788155. doi: 10.3389/fphar.2021.788155. eCollection 2021.

Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R. Increased global integration in the brain after psilocybin therapy for depression. Nat Med. 2022 Apr;28(4):844-851. doi: 10.1038/s41591-022-01744-z. Epub 2022 Apr 11.

Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021 Apr 15;384(15):1402-1411. doi: 10.1056/NEJMoa2032994.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03429075
• Other Study ID Numbers: 17HH3790; 2017-000219-18 ( EudraCT Number )
• First Posted: February 12, 2018
• Last Update Posted: July 31, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

depression; mdd; major depression; major depressive disorder; unipolar depression; psilocybin; psychedelics; psychedelic; escitalopram; ssri

Additional relevant MeSH terms:

Psilocybin; Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Pathologic Processes; Mood Disorders; Mental Disorders; Behavioral Symptoms; Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Hallucinogens