Randomised double-blind Phase II trial (n=59) comparing psilocybin versus escitalopram for major depressive disorder, assessing efficacy and mechanisms.
Randomised, double-blind, parallel-group study comparing psilocybin dosing days with daily escitalopram or placebo over a 6-week comparator period in adults with moderate-to-severe major depressive disorder.
Outcomes include clinical depression measures and mechanistic investigations (neuroimaging and related biomarkers); eligibility required HAM-D ≥17 and excluded current or familial psychotic disorders and significant medical contraindications.
Psilocybin dosing with daily placebo for comparator period.
Psilocybin administered on dosing days; daily placebo for 6 weeks.
Psilocybin dosing with daily escitalopram for comparator period.
Psilocybin administered on dosing days.
Escitalopram daily for 6 weeks (active comparator).
In a randomised trial of psilocybin-assisted therapy for moderate–severe depression, stronger therapeutic alliance and pre-session rapport predicted larger emotional‑breakthrough and mystical‑type experiences and were associated with greater symptom reduction. Emotional breakthrough during the first session and mystical experience during the second differentially contributed to improvement, while alliance before the second session had an additional direct effect on endpoint depression.