Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression
In a double‑blind randomized phase 2 trial for moderate-to-severe depression, both psilocybin therapy and escitalopram produced similar personality changes consistent with improved mental health (notably reduced neuroticism, disagreeableness and impulsivity, and increased openness), with only a possible selective increase in absorption after psilocybin. Changes following escitalopram were moderated by pre-trial positive expectancy, whereas expectancy did not moderate responses to psilocybin.
Authors
- Robin Carhart-Harris
- David Nutt
- David Erritzoe
Published
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.
Research Summary of 'Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression'
Introduction
Depression is a leading contributor to global disease burden, and recent clinical research has examined psychedelic-assisted therapies as potential interventions. Earlier trials have reported promising antidepressant effects of psilocybin therapy (PT), and one double-dummy, double-blind trial directly compared PT with escitalopram treatment (ET), finding PT superior on many secondary outcomes but not on the primary outcome. Personality traits, as captured by the Five-Factor Model (FFM), overlap with symptom dimensions of psychopathology and could therefore serve as complementary signals for understanding therapeutic mechanisms and broader functional outcomes beyond symptom change. Weiss and colleagues set out to compare the effects of PT versus ET on personality domains in a Phase II, randomized, double-blind, active-comparator trial of patients with moderate-to-severe major depressive disorder. Primary aims included testing within-condition personality change from baseline to six weeks and to six months, assessing between-condition differences in personality change, and examining moderators of personality change such as pre-trial treatment expectancy and acute psychological experiences during dosing. The study preregistered hypotheses that neuroticism, introversion, disagreeableness and impulsivity would decrease in both arms, and that openness would increase selectively in the PT arm; changes in absorption were treated as exploratory given limited prior data.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Weiss, B., Ginige, I., Shannon, L., Giribaldi, B., Murphy-Beiner, A., Murphy, R., Baker-Jones, M., Martell, J., Nutt, D. J., Carhart-Harris, R. L., & Erritzoe, D. (2024). Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression. Psychological Medicine, 54(1), 178-192. https://doi.org/10.1017/S0033291723001514
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