Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression
In a double-blind randomised trial (n=55) comparing escitalopram and COMP360 psilocybin for major depressive disorder, pre-treatment expectancy predicted response to escitalopram but not to psilocybin, whereas baseline trait suggestibility was associated with response to psilocybin only. These findings suggest psychedelic therapy may be less vulnerable to expectancy biases but could be particularly effective in highly suggestible individuals.
Authors
- Fernando Rosas
- Robin Carhart-Harris
- David Nutt
Published
Abstract
Background
To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).
Methods
We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.
Results
Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.
Conclusions
Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.
Research Summary of 'Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression'
Introduction
Depressive disorders are highly prevalent worldwide and current first-line treatments such as selective serotonin reuptake inhibitors (SSRIs) show only modest advantages over placebo. Psychedelic-assisted therapy, most prominently using psilocybin, has been proposed as an alternative approach in which one or two supervised dosing sessions interact with psychotherapeutic processes to produce therapeutic benefit. However, the conspicuous acute effects of psychedelics make effective blinding difficult, raising concerns that expectancy and related extra-pharmacological factors (for example demand characteristics or the Hawthorne effect) may bias outcomes in psychedelic trials. Szigeti and colleagues set out to examine whether pre-trial efficacy-related expectancy and baseline trait suggestibility and absorption were associated with therapeutic response in a previously conducted Phase II double-blind, randomised, parallel-group trial that compared escitalopram with investigational COMP360 psilocybin for moderate-to-severe major depressive disorder. The analysis aimed to determine whether expectancy effects differed between the two arms and whether suggestibility or absorption predicted response, with implications for the interpretation of comparative results between psilocybin therapy and standard pharmacotherapy.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Szigeti, B., Weiss, B., Rosas, F. E., Erritzoe, D., Nutt, D., & Carhart-Harris, R. (2024). Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression. Psychological Medicine, 54(8), 1717-1724. https://doi.org/10.1017/s0033291723003653
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