The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression
This Phase II, randomised, quadruple-blind, parallel-group, dose-ranging trial (n=233) evaluated the safety and efficacy of psilocybin in adults aged 18 and over with treatment-resistant depression (TRD). Sponsored by COMPASS Pathways and conducted across 25 sites in the United States, Canada, and multiple European countries, the study compared three psilocybin dose levels (low, medium, and high) to identify an optimal therapeutic dose for this population.
Detailed Description
Randomized, parallel-group, quadruple-blind, dose-ranging Phase II trial of psilocybin for treatment-resistant depression with three experimental dose arms (low, medium, high); psychotherapy provided alongside dosing.
Multi-centre study (sites in the United States, Canada and several European countries) assessing safety and efficacy outcomes in adults with TRD; actual enrolment reported as 233.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Low dose
experimentalLow dose Psilocybin.
Interventions
- Psilocybin1 mgvia Oral• single dose• 1 doses total
Dose-finding, low dose arm per protocol.
Medium dose
experimentalMedium dose Psilocybin.
Interventions
- Psilocybin10 mgvia Oral• single dose• 1 doses total
Dose-finding, medium dose arm per protocol.
High dose
experimentalHigh dose Psilocybin.
Interventions
- Psilocybin25via Oral• single dose• 1 doses total
Dose-finding, high dose arm per protocol.
Participants
Inclusion Criteria
- Participants meeting all the following inclusion criteria at Screening (V1) should be
- considered for admission into the study
- 1. Signed ICF.
- 2. 18 years of age or older at Screening (V1).
- 3. At least moderate MDD (single or recurrent episode as informed by DSM-5; if single episode, duration of ≥ 3 months and ≤ 2 years) based on medical records, clinical assessment and documented completion of the version 7.0.2 MINI.
- 4. HAM-D-17 (17-item) score ≥ 18 at Screening (V1) and at Baseline (V2).
- 5. Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatment for the current episode as determined through the MGH-ATRQ and using the supplementary advice on additional antidepressants not included in MGH-ATRQ (Appendix III). Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD in that country.
- 6. McLean Screening Instrument for Borderline Personality Disorder < 7 at
- Screening (V1).
- 7. Have successfully discontinued all antidepressant medications at least 2 weeks prior to Baseline (V2).
- 8. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.
Exclusion Criteria
- Participants meeting any of the following exclusion criteria at Screening (V1) will not be enrolled in the study.
- Psychiatric Exclusion Criteria:
- 1. Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).
- 2. Prior electroconvulsive therapy and/or ketamine for current episode.
- 3. Current cognitive behavioural therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of baseline.
- 4. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening (V1).
- 5. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, at Screening or at Baseline, or;
- (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during subject interview.
- 6. Depression secondary to other severe medical conditions.
- 7. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin, including exposure to psilocybin within the past year and use of psychedelics, such as ayahuasca, during the current depressive episode.
- General Medical Exclusion Criteria:
- 8. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of child bearing potential must have a negative urine pregnancy test at Screening (V1) and Baseline (V2).
- 9. Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF.
- 10. Uncontrolled insulin-dependent diabetes.
- 11. Seizure disorder.
- 12. Positive urine drug screen for illicit drugs or drugs of abuse at V1 and/or V2. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator’s discretion in conjunction with the medical monitor.
- 13. Current enrolment in any investigational drug or device study or participation in such within 30 days of Screening (V1).
- 14. Current enrolment in an interventional study for depression or participation in such within 30 days of Screening (V1).
- 15. Abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at Screening (V1).
- 16. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study
Primary Results(6 publications)
Participants
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Low doseexperimental | 79 | 66(83.5%) | 13(16.5%) | 10(12.7%) | 2(2.5%) |
| Medium doseexperimental | 75 | 56(74.7%) | 10(13.3%) | 6(8.0%) | 2(2.7%) |
| High doseexperimental | 79 | 57(72.2%) | 2(2.5%) | 1(1.3%) | 0(0.0%) |
| Low doseexperimental | 4 | — | — | — | — |
| Medium doseexperimental | 3 | — | — | — | — |
| High doseexperimental | 4 | — | — | — | — |
| Low doseexperimental | 26 | — | — | — | — |
| Medium doseexperimental | 24 | — | — | — | — |
| High doseexperimental | 27 | — | — | — | — |
| Low doseexperimental | 79 | — | — | — | — |
| Medium doseexperimental | 75 | — | — | — | — |
| High doseexperimental | 79 | — | — | — | — |
| Low doseexperimental | 79 | — | — | — | — |
| Medium doseexperimental | 75 | — | — | — | — |
| High doseexperimental | 79 | — | — | — | — |
| Low doseexperimental | 79 | — | — | — | — |
| Medium doseexperimental | 75 | — | — | — | — |
| High doseexperimental | 79 | — | — | — | — |
* teaeAny_n (84%) and teaeSerious_n (13% total across all periods) derived from text and Table 3. teaeDiscont_n refers to those discontinuing due to adverse events specifically. Suicidal ideation/behavior and self-injury are included in serious AE counts.
* teaeAny_n (75%) and teaeSerious_n (8% day 1 + 5% day 2-3 + 4% week 3-12) derived from text and Table 3. teaeDiscont_n refers to those discontinuing due to adverse events specifically.
* teaeAny_n (72%) and teaeSerious_n (1% day 1 + 1% day 2-3 + 1% week 3-12) derived from text and Table 3. teaeDiscont_n refers to those discontinuing due to adverse events specifically.
* 1 mg dose group (active control). Qualitative study of 11 participants; 4 were in this arm.
* 10 mg dose group. Qualitative study of 11 participants; 3 were in this arm.
* 25 mg dose group. Qualitative study of 11 participants; 4 were in this arm.
* 25 mg dose group (from Table 2). Safety summary counts not explicitly provided in the text/tables.
* 10 mg dose group (from Table 2). Safety summary counts not explicitly provided in the text/tables.
* 1 mg dose group (from Table 2). Safety summary counts not explicitly provided in the text/tables.
* Safety summary counts (TEAEs) not explicitly provided in the provided text/tables; only efficacy and psychedelic experience measures were reported.
* Safety summary counts not explicitly provided in the text or tables of this retrospective analysis paper.
* Safety data (TEAE counts) not reported in the provided text/tables; paper focuses on therapeutic alliance and psychedelic experience correlations.
Study Details
- StatusCompleted
- PhasePhase II
- Typeinterventional
- DesignRandomizedquadruple Blind
- Target Enrollment233 participants
- TimelineStart: 2019-01-01End: 2021-09-27
- Compounds
- Topic
Study Team
Sponsors & Collaborators
- COMPASS PathwaysPrimary Sponsor
Investigators
- EMEkaterina Malievskaia