Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

NCT03429075 | Completed Phase 2 Results

• 2 other identifiers: 17HH37902017-000219-18
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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).

Conditions

Depressive Disorder, Major

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage Change of the BOLD Signal

  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.

  Baseline measure vs 6 weeks post 1st psilocybin dosing

• Change in QIDS-16: Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-16)

  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)

  Baseline vs 6 weeks post 1st psilocybin dosing

Secondary Outcomes (5)

• Change in Hamilton Depression Scale (HAMD-17)

  Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose

• Change in Beck Depression Inventory (BDI-IA)

  Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose

• Change in MADRS

  Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose

• 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 "Remitted": QIDS-16 Remission Rate

  Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose

Study Arms (2)

Psilocybin

EXPERIMENTAL

Patients receive Psilocybin

Drug: Psilocybin + Placebo

Escitalopram

ACTIVE COMPARATOR

Patients receive Escitalopram

Drug: Psilocybin + Escitalopram

Interventions

Psilocybin + Placebo DRUG

Multiple dosing days psilocybin vs 6 weeks of daily placebo

Psilocybin

Psilocybin + Escitalopram DRUG

Multiple dosing days psilocybin vs 6 weeks of daily escitalopram

Escitalopram

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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. creatine clearance:renal clearance (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)

Sponsors & Collaborators

• Imperial College London: lead
• Alexander Mosely Charitable Trust: collaborator

Study Sites (1)

Imperial College Hammersmith campus

London, W12 0NN, United Kingdom

Location

Related Publications (8)

• 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.

  PMID: 29119217 BACKGROUND

• 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.

  PMID: 33852780 RESULT

• Erritzoe D, Barba T, Greenway KT, Murphy R, Martell J, Giribaldi B, Timmermann C, Murphy-Beiner A, Jones MB, Nutt D, Weiss B, Carhart-Harris R. Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. EClinicalMedicine. 2024 Sep 21;76:102799. doi: 10.1016/j.eclinm.2024.102799. eCollection 2024 Oct.

  PMID: 39764567 DERIVED

• Peill J, Marguilho M, Erritzoe D, Barba T, Greenway KT, Rosas F, Timmermann C, Carhart-Harris R. Psychedelics and the 'inner healer': Myth or mechanism? J Psychopharmacol. 2024 May;38(5):417-424. doi: 10.1177/02698811241239206. Epub 2024 Apr 12.

  PMID: 38605658 DERIVED

• Szigeti B, Weiss B, Rosas FE, Erritzoe D, Nutt D, Carhart-Harris R. Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression. Psychol Med. 2024 Jun;54(8):1717-1724. doi: 10.1017/S0033291723003653. Epub 2024 Jan 22.

  PMID: 38247730 DERIVED

• Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas FE, Peill JM, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris R. A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression. Psychedelic Med (New Rochelle). 2023 Mar;1(1):18-26. doi: 10.1089/psymed.2022.0002. Epub 2022 Oct 28.

  PMID: 37337526 DERIVED

• 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.

  PMID: 35431912 DERIVED

• 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.

  PMID: 35411074 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder

Interventions

Psilocybin; Escitalopram

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans

Results Point of Contact

• Title: Dr Robin Carhart-Harris
• Organization: Imperial College London

r.carhart-harris@imperial.ac.uk

02075947992

Study Officials

• David J Nutt, Medicine

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: February 12, 2018
• Study Start: January 7, 2019
• Primary Completion: April 17, 2020
• Study Completion: October 17, 2020
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)