Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.

In a double-blind trial comparing escitalopram and COMP360 psilocybin for major depressive disorder, patients held higher expectations for psilocybin than for escitalopram. Higher pre-trial expectancy for escitalopram predicted better outcomes with escitalopram, but expectancy for psilocybin did not predict response to psilocybin. Pre-treatment trait suggestibility was linked to therapeutic response in the psilocybin arm but not the escitalopram arm. These findings suggest that psychedelic therapy may be less influenced by expectancy biases than previously thought, and that highly suggestible individuals may be especially responsive to psilocybin treatment.

Study at a glance

Abstract

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). 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. 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. 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.