AzTrials
AzTrials

Depressive Disorder, MajorPhase 2Psilodep-RCTNCT03429075

Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

A Phase 2 study testing Psilocybin + Escitalopram in people with Depressive Disorder, Major, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Depressive Disorder, Major
What is being tested?
Psilocybin + Escitalopram
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
59 participants
Where
1 siteUnited Kingdom
Study dates
7 Jan 2019to 17 Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 18-80 years of age
  • Males and females
  • Sufficiently competent with English language

Who cannot join

  • 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
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Imperial College Hammersmith campus

    London, W12 0NN

Other trials in United Kingdom

About this study

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).

Being tested
Psilocybin + Placebo, Psilocybin + Escitalopram
Keywords
depression, mdd, major depression, major depressive disorder, unipolar depression, psilocybin, psychedelics, psychedelic, escitalopram, ssri
Medical subject headings
Depressive Disorder, Major, Depression, Depressive Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Psilocybin + PlaceboDrug

    Multiple dosing days psilocybin vs 6 weeks of daily placebo

  • Psilocybin + EscitalopramDrug

    Multiple dosing days psilocybin vs 6 weeks of daily escitalopram

Study groups in NCT03429075
Study groupRoleWhat they receive
PsilocybinExperimentalPatients receive Psilocybin
Receives: Drug: Psilocybin + Placebo
EscitalopramActive comparatorPatients receive Escitalopram
Receives: Drug: Psilocybin + Escitalopram

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline measure vs 6 weeks post 1st psilocybin dosing

  2. 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)

    Measured: Baseline vs 6 weeks post 1st psilocybin dosing

Secondary outcomes (5)

  1. Change in Hamilton Depression Scale (HAMD-17)

    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.

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

  2. Change in Beck Depression Inventory (BDI-IA)

    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.

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

  3. Change in MADRS

    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.

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

  4. Number of Patients Who "Responded": Quick Inventory of Depressive Symptomatology (QIDS-16) Response at 6 Weeks

    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.

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

  5. Number of Patients Who "Remitted": QIDS-16 Remission Rate

    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)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2018
  2. Study start7 Jan 2019
  3. Primary completion17 Apr 2020
  4. Study completion17 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03429075
Sponsor's protocol ID
17HH3790
Other IDs
2017-000219-18, 2017
Acronym
Psilodep-RCT
Status last verified
Aug 2024
First submitted
6 Dec 2017
Last updated
24 Oct 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 29119217

  • 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.

    PubMed 33852780

  • 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.

    PubMed 39764567

  • 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.

    PubMed 38605658

  • 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.

    PubMed 38247730

  • 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.

    PubMed 37337526

  • 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.

    PubMed 35431912

  • 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.

    PubMed 35411074

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Psilocybin + Escitalopram in people with Depressive Disorder, Major, run by Imperial College London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change of the BOLD Signal (time frame: Baseline measure vs 6 weeks post 1st psilocybin dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03429075, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in