Psilocybin vs escitalopram for depression
| ISRCTN | ISRCTN10584863 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10584863 |
| ClinicalTrials.gov (NCT) | NCT03429075 |
| Clinical Trials Information System (CTIS) | 2017-000219-18 |
| Integrated Research Application System (IRAS) | 221666 |
| Protocol serial number | IRAS ID: 221666, sponsor: 17HH3790 |
| Sponsor | Imperial College Joint Research Compliance Office (JRCO) |
| Funder | Alexander Mosely Charitable Trust |
- Submission date
- 03/08/2018
- Registration date
- 10/09/2018
- Last edited
- 28/06/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Depression is the leading cause of disability in the world, according to the World Health Organisation. Despite this, treatment of depression has not significantly advanced since the discovery and marketing of selective serotonin reuptake inhibitor drugs (SSRIs) in the 80s and 90s. While SSRIs work well for some people, many do not want to have to rely on taking them every day and can suffer a variety of side effects. Additionally, about 20% of people with major depression are “treatment-resistant”, meaning that no currently licensed anti-depressant treatment seems to work for them at all.
Psychedelic substances such as psilocybin (the active ingredient in so-called ‘magic mushrooms’) act via the same system of the brain as SSRIs. Between the 1940s and 1960s, before psychedelics were made illegal, nearly 2000 scientific papers were published on them, several of which suggested potential for treating disorders such as depression, addiction, PTSD, etc.
In 2016, we (the Psychedelic Research Group at Imperial College London) carried out a study where we provided 20 patients with severe treatment-resistant depression with psilocybin. This study was mostly focused on safety, but the results were encouraging, with 50% showed improvement after 3 weeks, with some patients in remission over a year later. This study aims to build on this research, comparing psilocybin with a standard SSRI, escitalopram. We want to look at the different effects that psilocybin and escitalopram on the brain's response to emotional faces, changes in depressive symptoms, anxiety, side-effects and personality.
Who can participate?
UK residents between the ages of 18-80 who have been diagnosed with moderate to severe unipolar major depressive disorder by a UK general practitioner
What does the study involve?
All participants will receive two doses of psilocybin, three weeks apart. Psilocybin dosages will vary across the study. Some participants will also take escitalopram for 6 weeks (10mg for 3 weeks then 20mg for a further 3 weeks) and the rest will take daily placebo capsules instead. The study is double-blind, so neither the participants nor the researchers will know what treatments each participant is receiving. All participants will be scanned before the first psilocybin dose and then 6 weeks later. There will be 7 study visits over the course of 3-4 months and participants will be expected to complete weekly questionnaires. There will also be a Skype interview 6 months after treatment and further monthly measures during that time period.
What are the possible benefits and risks of participating?
The possible benefit of taking part in this study is that the treatment may help to improve depressive symptoms; however, there is no guarantee of this. Additionally, enrolling in this research will help us understand more about the potential of psilocybin as a treatment for depression, contributing to knowledge that may help make this new form of therapy legal in the United Kingdom. It will also help us understand the differences in mechanisms between this new potential treatment and ones currently used in the NHS.
However, any participant who wishes to be involved must come off any anti-depressant medication they are currently on, which can take weeks and can be difficult. We will liaise with each participant’s GP to make sure that this is done safely. If participants are randomised into a group that will be taking escitalopram, they might experience side-effects associated with this drug. Common side effects include agitation, restlessness, diarrhoea, sleeping difficulties, dry mouth, headache, nausea, sexual difficulties, dizziness and sweating. Less common side effects include frequent urination, indigestion, increased or decreased appetite, taste alterations, shaking, tingling, weight changes, influenza-like symptoms and pain in neck or shoulders, serotonin syndrome, suicidal thinking and behaviour, abnormal bleeding, seizures, manic episodes, low sodium and angle closure glaucoma. Psilocybin has been shown to be quite safe within a research setting, and side-effects only include pre-dose anxiety and headaches the next day. This study requires a lot of time commitment and so we would like to make sure that participants are fully aware of this before they enrol.
Where is the study run from?
Imperial College Hammersmith Campus, London
When is the study starting and how long is it expected to run for?
January 2017 to October 2020
Who is funding the study?
Alexander Mosely Charitable Trust (UK)
Who is the main contact?
Ms Bruna Giribaldi
b.cunha@imperial.ac.uk
Contact information
Scientific
Imperial College London Hammersmith campus
Du Cane Rd
London
W12 0NN
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional double-blind randomised controlled phase II clinical trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Psilocybin versus escitalopram for major depressive disorder: comparative mechanisms |
| Study acronym | Psilodep |
| Study objectives | Primarily this study aims to compare the mechanisms by which the psychedelic substance psilocybin and the selective serotonin reuptake inhibitor (SSRI) escitalopram may exert antidepressant action in 50 patients with moderate-severe major depressive disorder. Specifically, the amygdala's BOLD (blood-oxygen-level-dependent signal) response to emotional faces in a functional magnetic resonance imaging (fMRI) task. |
| Ethics approval(s) | NRes Brent Research Ethics Committee, 31/07/2018, 17/LO/0389 |
| Health condition(s) or problem(s) studied | Moderate to severe major depressive disorder (17+ HAMD) |
| Intervention | After enrolment, patients are randomly assigned randomisation numbers by our unblinded team that will correspond to treatment arms. These numbers are provided to us by the company that labels the psilocybin bottles. Participants will be randomised into 2 groups. Participants in both groups will receive 2 doses of psilocybin, 3 weeks apart from each other. One group will then also receive a placebo for 6 weeks. The other group will receive 6 weeks of escitalopram (10 mg daily for 3 weeks, followed by 20 mg daily for the remaining 3 weeks). Participants will be asked to attend the study centre 7 times. Visit 1 is a screening, where participants will enrol on the study and sign informed consent. 2-4 weeks later, visit 2 will involve preparation for the first psilocybin dosing session and their first fMRI scan. Visit 3 will be 1 day later, where participants receive psilocybin for the first time, and either escitalopram or placebo capsules (depending on group allocation) to take daily for the next 6 weeks. Visit 4 will occur 1 day later, which involves a follow-up with study guides and therapists who were present at the psilocybin dosing session to discuss what they experience. 3 weeks after the first dose, visit 5 will involve the second psilocybin dosing session. Visit 6 is 1 day later, which again involves a follow-up with study guides and therapists who were present at the psilocybin dosing session. 3 weeks after the second dose, visit 7 will be a final follow-up and a second fMRI scan. Participants will be asked to complete weekly questionnaires for 6 months following the final session and to take part in a Skype interview 6 months after the final session. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Psilocybin Escitalopram |
| Primary outcome measure(s) |
Amygdala's BOLD-response to fearful faces in fMRI emotional faces task, assessed at the baseline (1 day before first psilocybin dose) and at final follow-up (6 weeks after first psilocybin dose) |
| Key secondary outcome measure(s) |
1. Self-rated depression, assessed using: |
| Completion date | 17/10/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | All |
| Target sample size at registration | 50 |
| Total final enrolment | 59 |
| Key inclusion criteria | 1. Major depressive disorder (DSM-IV) 2. Depression of moderate to severe degree (17+ on the 21-item HAM-D). 2. No MRI contraindications 3. No SSRI contraindications 4. Has a GP or other mental healthcare professional who can confirm diagnosis 5. Aged 18-80 6. 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) |
| Date of first enrolment | 10/09/2018 |
| Date of final enrolment | 04/03/2020 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
Commonwealth building
Du Cane Road
London
W12 0NN
London
W12 0NN
United Kingdom
Burlington Danes building
Du Cane Road
London
W12 0NN
London
W12 0NN
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 15/04/2021 | 28/06/2022 | Yes | No | |
| Results article | Increased global integration in the brain after psilocybin therapy for depression | 01/04/2022 | 28/06/2022 | Yes | No |
| Results article | Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression | 31/03/2022 | 28/06/2022 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Interim results article | 01/02/2018 | 28/06/2022 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
28/06/2022: Publication references added.
05/10/2020: The following changes have been made:
1.The intention to publish date has been changed from 01/12/2020 to 01/03/2021.
2. The final enrolment number has been added.
24/04/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/06/2020 to 04/03/2020.
2. The overall trial end date was changed from 01/07/2020 to 17/10/2020.
06/11/2019: Internal review.
