Clinical Trial Results:
Psilocybin vs. escitalopram for major depressive disorder: comparative mechanisms
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Summary
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EudraCT number |
2017-000219-18 |
Trial protocol |
GB |
Global end of trial date |
17 Oct 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jun 2022
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First version publication date |
12 Jun 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
17HH3790
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Additional study identifiers
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ISRCTN number |
ISRCTN10584863 | ||
US NCT number |
NCT03429075 | ||
WHO universal trial number (UTN) |
U1111-1195-4514 | ||
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
RGIT Imperial College London, Room 221, Medical School Building, St Marys campus, Norfolk Pl, London, United Kingdom, W2 1PG
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Public contact |
Carhart-Harris, Robin, Imperial College London, +44 02075946550, r.carhart-harris@imperial.ac.uk
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Scientific contact |
Carhart-Harris, Robin, Imperial College London, +44 02075946550, r.carhart-harris@imperial.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Oct 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Oct 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
How effective is a single dose of psilocybin for major depressive disorder against an an active gold-standard medical treatment (6-weeks of escitalopram)?
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Protection of trial subjects |
Patients had several hours of in-person and remote preparation sessions with at least one, often two, clinicians (psychiatrists, clinical psychologists or therapists) before receiving psilocybin. The day after their psilocybin sessions they also had several hours (as needed) of 'integration' therapy, a psychological debrief about their psilocybin experience and state of mine. They had a call one week later and could have up to 3 extra calls with their clinical team as required in between visits. They also had a final integration session before the end of the trial to discuss their trial experience, 3 weeks after their second psilocybin dose. They were supported by study psychiatrists, alongside GPs, to come off medication before and after trial (where relevant). There was a 24/7 contact phone number kept by the study psychiatrists.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Nov 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 59
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Worldwide total number of subjects |
59
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
59
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
All enrolled patients were self-referred. We also recruited via the Clinical Research Network. | |||||||||
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Pre-assignment
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Screening details |
Patients did an initial telephone screening and remote Hamilton Depression Scale (required a score of over 17) with study clinicians. We also required a GP confirmation of their medical history. They then did a face-to-face screening with ECG, blood tests, urine drugs, pregnancy and alcohol breath tests and MINI psychiatric exam, etc. | |||||||||
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
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Arms
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Arm title
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Baseline - all patients | |||||||||
Arm description |
All patients before they were randomised into arms. | |||||||||
Arm type |
Baseline | |||||||||
Investigational medicinal product name |
No products in baseline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Unknown use
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Dosage and administration details |
No products at baseline.
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Period 2
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Period 2 title |
6 week trial period
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Is this the baseline period? |
No | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Psilocybin | |||||||||
Arm description |
Patients had two sessions with high doses of psilocybin (25mg), 3 weeks apart. After the first dose, they were given tablets of placebo to take 1 a day for 3 weeks, then 2 a day for another 3 weeks. All other study procedures were the same across arms. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Psilocybin 25mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
5 capsules with 5mg of psilocybin each, 25mg in total
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Arm title
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Escitalopram | |||||||||
Arm description |
Patients had two sessions with very low (virtually placebo) doses of psilocybin (1mg), 3 weeks apart. After the first dose, they were given tablets of the selective serotonin reuptake inhibitor (SSRI) escitalopram to take 1 a day for 3 weeks (10mg), then 2 a day for another 3 weeks (20mg). All other study procedures were the same across arms. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Escitalopram
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Investigational medicinal product code |
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Other name |
Lexapro, Cipralex
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Daily 10mg capsules of escitalopram for 3 weeks, then daily 20mg (2 capsules) of escitalopram for 3 weeks.
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Investigational medicinal product name |
Psilocybin 1mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
5 capsules, one with 1mg psilocybin and the others with placebo (made to look identical to the 25mg psilocybin arm)
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Baseline characteristics reporting groups
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Reporting group title |
Baseline - all patients
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Reporting group description |
All patients before they were randomised into arms. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Baseline - all patients
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Reporting group description |
All patients before they were randomised into arms. | ||
Reporting group title |
Psilocybin
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Reporting group description |
Patients had two sessions with high doses of psilocybin (25mg), 3 weeks apart. After the first dose, they were given tablets of placebo to take 1 a day for 3 weeks, then 2 a day for another 3 weeks. All other study procedures were the same across arms. | ||
Reporting group title |
Escitalopram
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Reporting group description |
Patients had two sessions with very low (virtually placebo) doses of psilocybin (1mg), 3 weeks apart. After the first dose, they were given tablets of the selective serotonin reuptake inhibitor (SSRI) escitalopram to take 1 a day for 3 weeks (10mg), then 2 a day for another 3 weeks (20mg). All other study procedures were the same across arms. | ||
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End point title |
Quick Inventory of Depressive Symptomatology (QIDS-SR-16) | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Change from baseline to 6 weeks after the first psilocybin session.
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Statistical analysis title |
ANCOVA | |||||||||||||||
Comparison groups |
Escitalopram v Psilocybin
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Number of subjects included in analysis |
59
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.17 | |||||||||||||||
Method |
ANCOVA | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
-2
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-5 | |||||||||||||||
upper limit |
0.9 | |||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1
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Adverse events information
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Timeframe for reporting adverse events |
6 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Psilocybin arm
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Escitalopram arm
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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21 Nov 2017 |
Various changes to conduct of trial: arm number (3 to 2), patient number (to 50), length of trial, etc. |
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18 May 2018 |
Various changes: extra psilocybin dose, primary end-point change from 4 weeks to 6 weeks, extra visit, extra questionnaires, changes required by HRA and MHRA. |
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13 Jul 2018 |
To MHRA: change in escitalopram dosing (all tablets given after first psilocybin dose), addition of Fisher as site of QP certification and Milpharm Limited as MA holder number. |
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31 Jul 2018 |
To REC: changes to adverse event reporting, adding a scale, change in escitalopram dosing (receive all tablets at once after DD1). |
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08 Jan 2019 |
To REC only: poster/flyer/text message templates for recruitment (suggested by Clinical Research Network), addition of press release details, patient contact cards and 2 new questionnaires |
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22 Feb 2019 |
To REC only: new documents (PIS, consent form etc) relating to documentary about trial (patients only see these new documents after they have left trial). Changes to protocol concerning documentary and inclusion of more rescue meds. |
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19 Aug 2019 |
To REC only: increase recruitment goal to 60 completers, new recruitment form and addition of 1m follow-up interview |
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03 Sep 2019 |
To MHRA only: increasing study completers from 50 to 60. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/33852780 |
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