Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial.

Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression. We examined the feasibility of administering a single 25-mg dose of psilocybin or placebo with psychological support in a randomized controlled trial design with 6 weeks of follow-up. A two-arm, double-blind, randomized, placebo-controlled feasibility trial was conducted at one National Health Service (NHS) site in England. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for major depressive disorder and had an inadequate response to ≥2 antidepressant treatments or ≥1 antidepressant plus ≥1 psychotherapy. Participants received 25-mg psilocybin or placebo with preparation, dosing support and integration. Primary outcomes were recruitment, retention and estimation of the Montgomery-Åsberg Depression Rating Scale (MADRS) variance. A multilevel regression analysis with an intention-to-treat population was used. Sixty participants were randomized (1:1), balanced by age, sex and prior psilocybin exposure, and 59 of 60 participants completed the MADRS at all follow-up visits. The adjusted between-group difference at week 3 on the MADRS was -10.41 (95% confidence interval: -14.86 to -5.95; Cohen's d = -1.70), favoring psilocybin, which was sustained at week 6. In total, 123 and 164 nonserious adverse events occurred in the placebo and psilocybin arms, respectively. Findings support a future confirmatory trial. EudraCT no.: 2018-003573-97 .