A randomised, placebo controlled trial of psilocybin in treatment resistant depression: A feasibility study

INTERVENTION: Product Name: Psilocybin Pharmaceutical Form: Capsule INN or Proposed INN: Psilocybin CAS Number: 520‐52‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Major depressive disorder ; MedDRA version: 21.1 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 ‐ Psychiatric disorders Therapeutic area: Psychiatry and Psychology [F] ‐ Mental Disorders [F03] PRIMARY OUTCOME: Main Objective: To evaluate the feasibility of a randomised, controlled trial design, in which a single dose of psilocybin 25mg PO vs placebo, is given to adult participants with treatment resistant major depressive disorder (TRD), under psychologically supportive conditions, with 6 weeks of follow up, by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS) to inform upon the design of a phase 3 trial. Primary end point(s): Recruitment rates, dropout rates and estimation of the variance of the primary outcome measure (MADRS).; ; Secondary Objective: 1)To assess the clinician‐rated efficacy of psilocybin 25mg compared to placebo via:; a)The change in the MADRS total score from Baseline to 3 weeks after treatment; b)The proportion of participants who demonstrate a response to treatment( =50% decrease in MADRS total score) from Baseline to Week 3. ; c)proportion of participants in remission( MADRS total score =10 at Week 3); 2)To assess the participant‐rated efficacy of psilocybin 25mg compared to placebo via:; a)proportion of participants who demonstrate a response to treatment, ( a =50% decrease in QIDS‐SR‐16 total score) from Baseline (V2) to Week 3 (V6).; b)proportion of participants in remission, where remission is defined as a QIDS‐SR‐16 total score =5 at Week 3. ; 3)To evaluate the safety and tolerability of psilocybin in participants with TRD based on adverse events (AEs), changes in vital signs and suicidal ideation/behaviour (measured using the Columbia Suicide Severity Rating Scale).; Timepoint(s) of evaluation of this end point: 3 weeks after dosing SECONDARY OUTCOME: Secondary end point(s): 1) The change in the Montgomery‐Asberg Depression Rating Scale total score from the Baseline Visit (V2 ‐ 1 day prior to treatment) to Week 3 after treatment (V6). ; 2) The proportion of participants who demonstrate a response to treatment, where response to treatment is defined as a =50% decrease in MADRS total score from Baseline to Week 3. ; 3) The proportion of participants in remission, where remission is defined as a MADRS total score =10 at Week 3. ; 4) The proportion of participants who sustain a response up to Week 6, where response is defined as those with =50% decrease in MADRS total score on or before Week 3 and remaining at Week 6.; 5) Time to event measures: restart antidepressant medication for any reason, restart medication for continuing depressive symptoms or relapse from a previously recovered state (clinical judgement, supported by the QIDS‐SR‐16). Participants who withdraw from the study will be censored from the time to event analysis.; ; Exploratory endpoints:; 1) Change from baseline (V2) in the following outcome measures; a) The WSAS at week 6 (V7); b) The QIDS‐SR‐16 at week 3 (V6); c) The GAD‐7 at week 3 (V6); Timepoint(s) of evaluation of this end point: As above INCLUSION CRITERIA: • Age 25 ‐ 80 years • Fluent in the English language • Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM‐5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features as defined on the MINI 7.0. Positive and primary diagnoses on the MINI 7.0 will be subject to confirmation at clinical interview by a psychiatrist. • 17‐item HAM‐D score = 14. • Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence‐based psychotherapy given for at least 6 sessions. • For those aged = 60 years, the first episode of depression must have started prior to their 60th birthday. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64