Trial Outcomes & Findings for Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms (NCT NCT03429075)
NCT ID: NCT03429075
Last Updated: 2024-10-24
Results Overview
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.
COMPLETED
PHASE2
59 participants
Baseline measure vs 6 weeks post 1st psilocybin dosing
2024-10-24
Participant Flow
Participant milestones
| Measure |
Psilocybin
Patients receive two doses of 25mg psilocybin, 3 weeks apart. After the first dose of 25mg psilocybin, patients start taking one daily placebo tablet every morning for 3 weeks. After their second 25mg psilocybin session, patients start taking two daily placebo tablets for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
Escitalopram
Patients receive two doses of 1mg psilocybin (considered to be virtually placebo), 3 weeks apart. After the first dose of 1mg psilocybin, patients start taking one daily 10mg escitalopram tablet every morning for 3 weeks. After their second 1mg psilocybin session, patients start taking two daily tablets of escitalopram (10mg each, 20mg in total) for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
29
|
|
Overall Study
COMPLETED
|
30
|
29
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms
Baseline characteristics by cohort
| Measure |
Psilocybin
n=30 Participants
Patients receive two doses of 25mg psilocybin, 3 weeks apart. After the first dose of 25mg psilocybin, patients start taking one daily placebo tablet every morning for 3 weeks. After their second 25mg psilocybin session, patients start taking two daily placebo tablets for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
Escitalopram
n=29 Participants
Patients receive two doses of 1mg psilocybin (considered to be virtually placebo), 3 weeks apart. After the first dose of 1mg psilocybin, patients start taking one daily 10mg escitalopram tablet every morning for 3 weeks. After their second 1mg psilocybin session, patients start taking two daily tablets of escitalopram (10mg each, 20mg in total) for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=93 Participants
|
29 Participants
n=4 Participants
|
59 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
43.3 years
STANDARD_DEVIATION 11.7 • n=93 Participants
|
39.1 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
41.2 years
STANDARD_DEVIATION 10.9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
28 participants
n=93 Participants
|
24 participants
n=4 Participants
|
52 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=93 Participants
|
4 participants
n=4 Participants
|
5 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Mixed Asian + White
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
30 participants
n=93 Participants
|
29 participants
n=4 Participants
|
59 participants
n=27 Participants
|
|
No previous psilocybin use
|
22 participants
n=93 Participants
|
21 participants
n=4 Participants
|
43 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline measure vs 6 weeks post 1st psilocybin dosingPopulation: The data obtained from an imaging group in the trial, in which functional MRI was used to predict responses to the trial drugs, have not been analyzed.
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.
Outcome measures
| Measure |
Psilocybin
n=25 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=21 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Percentage Change of the BOLD Signal
|
-0.08 percentage change in BOLD signal
Standard Deviation 0.45
|
0.43 percentage change in BOLD signal
Standard Deviation 0.62
|
PRIMARY outcome
Timeframe: Baseline vs 6 weeks post 1st psilocybin dosingChange 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)
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Change in QIDS-16: Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-16)
|
-8 score on a scale
Standard Error 1
|
-6 score on a scale
Standard Error 1
|
SECONDARY outcome
Timeframe: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin doseHAMD-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.
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Change in Hamilton Depression Scale (HAMD-17)
|
-10.5 units on a scale
Standard Error 1
|
-5.1 units on a scale
Standard Error 1
|
SECONDARY outcome
Timeframe: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin doseBDI-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.
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Change in Beck Depression Inventory (BDI-IA)
|
-18.4 units on a scale
Interval -22.6 to -13.8
|
-10.8 units on a scale
Interval -14.3 to -7.3
|
SECONDARY outcome
Timeframe: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin doseMADRS - 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.
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Change in MADRS
|
14.4 score on a scale
Standard Error 1.7
|
-7.2 score on a scale
Standard Error 1.7
|
SECONDARY outcome
Timeframe: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin doseNumber 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.
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Number of Patients Who "Responded": Quick Inventory of Depressive Symptomatology (QIDS-16) Response at 6 Weeks
|
21 participants
|
14 participants
|
SECONDARY outcome
Timeframe: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin doseNumber 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)
Outcome measures
| Measure |
Psilocybin
n=30 Participants
Patients receive Psilocybin
Psilocybin + Placebo: Multiple dosing days psilocybin vs 6 weeks of daily placebo
|
Escitalopram
n=29 Participants
Patients receive Escitalopram
Psilocybin + Escitalopram: Multiple dosing days psilocybin vs 6 weeks of daily escitalopram
|
|---|---|---|
|
Number of Patients Who "Remitted": QIDS-16 Remission Rate
|
17 participants
|
8 participants
|
Adverse Events
Psilocybin
Escitalopram
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Psilocybin
n=30 participants at risk
Patients receive two doses of 25mg psilocybin, 3 weeks apart. After the first dose of 25mg psilocybin, patients start taking one daily placebo tablet every morning for 3 weeks. After their second 25mg psilocybin session, patients start taking two daily placebo tablets for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
Escitalopram
n=29 participants at risk
Patients receive two doses of 1mg psilocybin (considered to be virtually placebo), 3 weeks apart. After the first dose of 1mg psilocybin, patients start taking one daily 10mg escitalopram tablet every morning for 3 weeks. After their second 1mg psilocybin session, patients start taking two daily tablets of escitalopram (10mg each, 20mg in total) for another 3 weeks.
All tablets are identical and visit procedures are identical otherwise.
|
|---|---|---|
|
Nervous system disorders
Headache
|
66.7%
20/30 • 6 weeks
|
51.7%
15/29 • 6 weeks
|
|
Gastrointestinal disorders
Nausea
|
26.7%
8/30 • 6 weeks
|
31.0%
9/29 • 6 weeks
|
|
General disorders
Fatigue
|
6.7%
2/30 • 6 weeks
|
24.1%
7/29 • 6 weeks
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/30 • 6 weeks
|
13.8%
4/29 • 6 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/30 • 6 weeks
|
13.8%
4/29 • 6 weeks
|
|
Nervous system disorders
Migraine
|
10.0%
3/30 • 6 weeks
|
3.4%
1/29 • 6 weeks
|
|
Cardiac disorders
Palpitations
|
3.3%
1/30 • 6 weeks
|
10.3%
3/29 • 6 weeks
|
|
Psychiatric disorders
Sleep disorder
|
3.3%
1/30 • 6 weeks
|
10.3%
3/29 • 6 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
1/30 • 6 weeks
|
6.9%
2/29 • 6 weeks
|
|
General disorders
Feeling abnormal
|
0.00%
0/30 • 6 weeks
|
10.3%
3/29 • 6 weeks
|
|
General disorders
Feeling jittery
|
6.7%
2/30 • 6 weeks
|
3.4%
1/29 • 6 weeks
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
2/30 • 6 weeks
|
3.4%
1/29 • 6 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place