New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy

A Phase II trial comparing psilocybin-assisted therapy with escitalopram for depression found no statistically significant difference on the primary outcome measure (QIDS-SR16), though secondary measures favored psilocybin. Expert commentaries noted possible issues with the choice of primary outcome, statistical power, and the limitations of depression rating scales in capturing improved mood and well-being. This opinion piece, drawing on the authors' experiences in psychedelic trials and NHS psychiatry, argues that psychedelic therapies will both open new frontiers and face a bursting bubble, exploring the stakes and opportunities involved.

Study at a glance

Abstract

The publication in April 2021 of the Imperial College London Phase II study investigating \nthe efficacy of psilocybin-assisted therapy vs. escitalopram for depression reported differences \nin the primary outcome measure (the QIDS-SR16) between experimental and control arms as \nstatistically insignificant (1). However, secondary measures of depression, and other relevant \nmeasures (see Appendix), favored psilocybin to escitalopram. Soon thereafter, a range of expert \ncommentaries offered interpretations, including that the researchers were unfortunate in their \nchoice of pre-registered primary outcome, the trial was underpowered perhaps revealing an \noverconfidence in designing the study, and the limitations of depression rating measures to capture \nthe return of positive mood and well-being. \nPartially in response to these publications, discussions in research and online communities \nhave grown around the over-hyping of psychedelic treatments, bringing into focus concerns over \npsychedelic therapy trial methodology [for a peer-reviewed critique, see (2)]. This opinion piece \nexplores these concerns to propose a response to this special issue’s question, “Can Psychedelic \nTherapies Open a New Frontier in Mental Healthcare (Or Will the Bubble Burst)?” Drawing on \nour experiences of working within psychedelic clinical trials and NHS psychiatry, we offer here a \ndeflationary answer to this question, suggesting both will occur and outlining some of the facets, \nstakes and opportunities entailed.