Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.

In a trial comparing psilocybin therapy with the antidepressant escitalopram for moderate-to-severe major depressive disorder, both treatments led to personality changes in a direction consistent with improved mental health. Psilocybin was linked to decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness at six weeks, with some changes lasting six months. Escitalopram was linked to decreases in neuroticism, disagreeableness, and impulsivity, and increases in openness at six weeks, with neuroticism remaining decreased at six months. No significant differences between the two treatments were observed, except that patients' pre-trial positive expectations for escitalopram moderated personality changes after that treatment, but not after psilocybin.

Study at a glance

Abstract

Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up. PT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed. Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.