Psilocybin in Participants with Treatment Resistant Depression (P-TRD)
Research type
Research Study
Full title
The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression (P-TRD)
IRAS ID
235360
Contact name
Susan C. Stansfield
Contact email
Sponsor organisation
COMPASS Pathways, Ltd
Eudract number
2017-003288-36
Duration of Study in the UK
1 years, 6 months, 30 days
Research summary
Research Summary
A recent open label study of the effects of psilocybin in participants with treatment resistant depression (TRD) showed rapid significant decrease of depressive symptoms after treatment with psilocybin coupled with psychological support. Over 40% of participants sustained response at 3 months. In this study, the aim is to assess effectiveness of 3 different doses of psilocybin (1 mg, 10 mg, and 25 mg) in TRD.
Summary of Results
The research was funded and sponsored by COMPASS Pathfinder Ltd. (a subsidiary of COMPASS Pathways).
BACKGROUND
Treatment-resistant depression (TRD) is diagnosed in patients who have taken treatment for depression that did not fully help with symptoms. COMP360 is a man-made form of the naturally occurring chemical compound, psilocybin. Psilocybin is found in some species of mushrooms, commonly known as “magic mushrooms”. COMP360 is synthetically produced in a laboratory and not taken from the mushroom itself. Research suggests that psilocybin may help in treating depression. Psilocybin (and therefore COMP360) works on the serotonin system in the brain which is linked to several important functions in our body, including regulation of mood, sleep, and thinking processes. Psilocybin is a psychedelic and controlled drug, and its use outside of approved research is prohibited by law. COMPASS conducted this current study to determine the correct dose of COMP360 psilocybin for use in patients with TRD. This study has received all required approvals and it is legal for participants to be given psilocybin in the form of COMP360 in this study.PURPOSE OF THE STUDY
In this study, researchers tested how well COMP360 psilocybin works (administered in a supportive setting with a therapist present) to reduce depressive symptoms. They did this by comparing the effect of 10 mg or 25 mg with a lower dose of 1 mg of COMP360 psilocybin.The main purposes of this study were:
• To determine if COMP360 psilocybin given at 25 mg or 10 mg reduces depressive symptoms to a greater extent than COMP360 psilocybin given at 1 mg.
• To obtain more information about the safety of COMP360 psilocybin in participants with TRD.STUDY DESIGN AND RESEARCH METHODOLOGY
• The study was conducted between January 2019 and September 2021 in Canada, Czech Republic, Denmark, Germany, Ireland, Netherlands, Portugal, Spain, United Kingdom, and United States.
• The study was a double-blind research study; meaning neither the participant, nor the study doctor, therapist, other study staff, and those rating the Montgomery-Åsberg depression rating scale (MADRS) knew which dose of psilocybin they were getting. MADRS is a widely used clinician rated measure consisting of 10 individual items of the severity of depression. Each of the 10 items in the MADRS has a score ranging from 0 (normal) to 6 (severe), with higher scores denoting greater severity. The MADRS total score (ranging from 0-60) is derived from summing up the scores from the 10 individual items.
• The dose received by participants was decided by chance (randomly, like flipping a coin).
• During a 3- to 6-week screening period, participants were expected to reduce any antidepressant and/or antipsychotic medications and to have completely discontinued these medications at least 2 weeks before COMP360 psilocybin treatment.
• Participants met a therapist for a minimum of three preparation visits prior to the COMP360 psilocybin administration session. Preparation visits covered what to expect during the COMP360 administration sessions, and review of psychoeducation materials at the time of enrolment. The COMP360 psilocybin administration session lasted approximately 6 to 8 hours and was supported by trained therapists.
• After the acute (intense) effects of the psilocybin passed, participants were evaluated for safety and accompanied home.
• On Day 2, the day following the COMP360 psilocybin administration session, participants were seen in person for a safety check, including assessment of suicide risk, and to discuss their experience during the COMP360 psilocybin administration session.
• All participants were asked to remain off their antidepressant medications for at least 3 weeks following the COMP360 psilocybin administration session. Rescue medications (medications used to relieve depression) were allowed.
• Participants were seen at the clinic for:
o Screening (plus a minimum of three safety visits)
o Baseline (Day -1)
o Day 1 (COMP360 psilocybin administration session)
o Day 2, Week 1, Week 2, Week 3, and Week 12.
• Participants were contacted for remote follow-up at 6 and 9 weeks after treatment.
• The MADRS was assessed by a remote assessor who was unaware of the compound being studied or what study the participant was participating in. Other assessments and safety measures were completed electronically by the participant and by the clinician.STUDY PARTICIPANTS
Some requirements to take part in the study were that participants:
• Were at least 18 years of age and had TRD with at least moderate major depressive disorder (a condition characterised by a persistently depressed mood and long-term loss of pleasure or interest in life) and failure to respond to two to four prior treatments for their current depressive episode.
• Had a McClean Screening Instrument for Borderline Personality Disorder (MSI BDP [a measure used to assess BPD]) score <7 at Screening (Scores range from 0 to 10 and a score of 7 indicates a likelihood for the participant to meet the criteria of borderline personality disorder).
• Were required to discontinue antidepressant medications at least 2 weeks prior to Baseline.Participants meeting any of the following exclusion criteria at screening were not enrolled into the study.
• 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, or borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and structured clinical interview.
• Current (within the previous year) alcohol or substance abuse.
• Significant suicide risk.
• Prior electroconvulsive therapy (a treatment that involves sending an electric current through the brain, causing a brief surge of electrical activity within the brain) and/or ketamine for current episode.RESULTS
Demography and Baseline characteristics
• A total of 233 participants were treated and 209 (89.7%) participants completed the study.
o 112 participants were male and 121 were female.
o Ages were from 18 to 84 years. The average age was 39.8 years.
o Participants were mostly White (92.3%).
o The majority of participants (94.0%) had no previous experience of psilocybin.Efficacy
• There was a clinically relevant and statistically significant improvement of 6.6 points from baseline in the MADRS total score at Week 3 in the COMP360 psilocybin 25 mg treatment group compared with the COMP360 psilocybin 1 mg treatment group.
• The difference between the COMP360 psilocybin 10 mg and COMP360 psilocybin 1 mg treatment groups was not statistically significant.
• More than twice as many participants in the COMP360 psilocybin 25 mg treatment group had a response (defined as a ≥50% improvement in MADRS total score from baseline) at Week 3 compared with the COMP360 psilocybin 1 mg treatment group. This difference was considered clinically meaningful.
• The proportion of participants who were responders (defined as ≥50% improvement from baseline MADRS score [%]) at Week 3 in the COMP360 psilocybin 10mg treatment group was similar to the COMP360 psilocybin 1mg treatment group.
• A higher proportion of participants in the COMP360 psilocybin 25 mg treatment group were in remission (defined as a MADRS total score ≤10 at a post-baseline visit) at Week 3 compared with the COMP360 psilocybin 1mg treatment group. This difference was considered clinically meaningful.
• A higher proportion of participants in the COMP360 psilocybin 25 mg treatment group had a sustained response at Week 12 (defined as a ≥50% improvement in MADRS total score from baseline at any visit up to and including Week 3, and at all visits after Week 3 until Week 12) compared with the psilocybin 1 mg treatment group.
• The proportion of participants whose symptoms had reduced (ie were remitters) at Week 3 and who were sustained responders at Week 12 in the COMP360 psilocybin 10 mg treatment group was similar to the COMP360 psilocybin 1 mg treatment group.
• Additional measures of anxiety, self-report depression, quality of life, and functioning supported the above findings.Safety
• Overall, COMP360 psilocybin treatment was well tolerated.
• Treatment-emergent adverse events (TEAEs [an undesired effect with a start date on or after COMP360 psilocybin administration]) were reported for the majority of participants in each treatment group, including 66 (83.5%), 56 (74.7%) and 57 participants (72.2%) in the COMP360 psilocybin 25 mg, 10 mg and 1 mg treatment groups, respectively.
• TEAEs were mostly mild or moderate in severity and not serious.
• Serious (seriousness is based on participant/event outcome at the time of the event) TEAEs were reported for 12 participants (5.2%).
• Overall, there was a higher rate of serious adverse events (an occurrence that is considered to represent a significant hazard to the participant) in the COMP360 psilocybin 25 mg and 10 mg treatment groups compared with the COMP360 psilocybin 1 mg group (five participants [6.3%] and six participants [8.0%], respectively; compared with one participant [1.3%] in the COMP360 psilocybin 1 mg group).
• Reported Treatment-emergent serious adverse events were most commonly in the psychiatric disorders. The most common events were related to suicidality and self injury.
• For participants with TEAEs that started on the day of dosing, the majority (81/113) resolved within one day.
• TEAEs that started on subsequent days tended to have longer before TEAE resolution, with the majority of participants with TEAEs with an onset after Day 8 (85/108) taking longer than a week to resolve.
• There were no deaths in this study.
• There were no significant safety findings from clinical laboratory or vital signs assessments.
• Abnormal electrocardiogram (a non-invasive test that measures the electrical activity of the heart) readings were reported for 23 participants (9.9%), including one participant with a clinically significant irregular heart rhythm (QTc interval prolongation) that was reported as a nonserious TEAE of mild intensity.
FUTURE RESEARCH PLANNED:
Longer and larger studies are required to determine the efficacy and safety of COMP360 psilocybin for TRD.REC name
London - Brent Research Ethics Committee
REC reference
18/LO/0287
Date of REC Opinion
9 Mar 2018
REC opinion
Favourable Opinion