Psilocybin with therapy for treatment-resistant depression in an NHS clinic: an RCT

The question

Can a single 25-mg dose of psilocybin, given alongside psychological support, be delivered within a public health service, and how do depression scores compare with placebo?

What they did

Sixty adults with major depressive disorder who had not responded adequately to at least two antidepressant treatments, or to one antidepressant plus one course of psychotherapy, took part at a single NHS site in England. They were randomly assigned, half and half, to a single 25-mg dose of psilocybin or a placebo, with preparation sessions before, support during dosing and integration sessions afterwards. Neither participants nor staff knew who got what. The main aims were to test recruitment, retention and how much depression scores varied, with follow-up to six weeks.

What they found

Fifty-nine of the 60 participants completed the depression rating scale (MADRS) at every follow-up visit. At week 3, the psilocybin group scored 10.41 points lower on the MADRS than the placebo group after adjustment (95% confidence interval: -14.86 to -5.95; Cohen’s d = -1.70), a difference that was still present at week 6. There were 164 non-serious adverse events in the psilocybin arm and 123 in the placebo arm. The authors conclude the results support running a larger confirmatory trial.

The fine print

This was a feasibility trial designed mainly to test recruitment and retention, not to prove effectiveness, and 60 people is a small sample for judging benefit. Follow-up stopped at six weeks, so nothing is known about longer-term effects. Psychedelic effects are hard to hide, so participants may have guessed their assignment despite the blinding. This summary is based on the abstract alone.

What it means

In a public healthcare setting, a single dose of psilocybin with psychological support was feasible to deliver and was followed by larger drops in depression scores than placebo over six weeks, but a bigger trial is needed before firm conclusions can be drawn.

Evidence grade: Moderate. A randomized, double-blind, placebo-controlled trial, but a small feasibility study at a single site with only six weeks of follow-up.

This summary is based on the study’s published abstract.