Six-Month Follow-Up Data Shows Psilocybin Outperforms Escitalopram… or Does It?

Last Saturday, 6-month follow-up data from Imperial College London’s psilocybin vs. escitalopram in major depressive disorder (MDD) study was published (Erritzoe et al., 2024).

As a reminder, the original study saw participants randomised to receive either two separate 25 mg doses of psilocybin 3 weeks apart plus daily placebo for 6 weeks (N=30), or two separate 1 mg doses of psilocybin 3 weeks apart plus daily oral escitalopram for 6 weeks (N=29). All participants received psychological support during the trial. The study’s primary outcome was change in QIDS-SR-16 (a 16-item self-report scale of depressive symptoms) scores from baseline at week 6. (More information on the protocol is available via its EU Clinical Trials Register¹ entry: 2017-000219-18.)

The original, 6-week data from the trial was published back in April 2021 (gosh, time flies!) in the prestigious New England Journal of Medicine (Carhart-Harris et al., 2021). That publication revealed that there was very little difference observed in the QIDS-SR-16 scores at week 6 among the two groups, with a between-group difference of two points, which was not statistically significant. That means that the results were inconclusive.

Those who watched BBC’s The Psychedelic Drug Trial documentary will have seen the apparent moment that lead author Robin Carhart-Harris presented the results to co-author and UK psychedelic research and policy reform powerhouse David Nutt. Nutt and Carhart-Harris highlighted the rapid-acting nature of psilocybin’s antidepressant effect in the study, but Nutt noted that “escitalopram caught up after six weeks.” It was hard not to read their reactions as somewhat disappointed, but putting on brave faces.

At the time of the study’s publication we wrote: “the results don’t appear to have met the lofty expectations of many.” (See our April 2021 coverage, Special Edition: Psilocybin vs. SSRI, for more.)

Despite an air of disappointment among psychedelic advocates and others who were riding the psychedelic hype bubble at the time, lead author Robin Carhart-Harris told NBC News that the team at Imperial “were honestly surprised that psilocybin performed as well as it did”. During his media rounds back in 2021, he also focused on the secondary outcomes collected in the study, which generally showed psilocybin in a more positive light than escitalopram.