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

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 ( = -0.63), introversion ( = -0.38), disagreeableness ( = -0.47), impulsivity ( = -0.40), and increases in absorption ( = 0.32), conscientiousness ( = 0.30), and openness ( = 0.23) at week 6, with neuroticism ( = -0.47) and disagreeableness ( = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism ( = -0.38), disagreeableness ( = -0.26), impulsivity ( = -0.35), and increases in openness ( = 0.28) at week 6, with neuroticism ( = -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 ( 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.