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

Abstract Background 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. Methods 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. Results 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. Conclusions 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.