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

Brandon Weiss, Induni Ginige, Lu Shannon, Bruna Giribaldi, Ashleigh Murphy-Beiner, Roberta Murphy, Michelle Baker-Jones, Jonny Martell, David Nutt, Robin Carhart-Harris, David Erritzøe

Psychological Medicine 2024 DOI: 10.1017/s0033291723001514 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Phase 2, double-blind, randomized, active comparator controlled trial Peer reviewed
Population Patients with moderate-to-severe major depressive disorder
Interventions Psilocybin therapy Escitalopram
Duration 6-week core trial period with follow-up at month 6
Topics Psilocybin Depression
Keywords Absorption Escitalopram Five-factor model Impulsivity Personality change Psilocybin therapy Psychedelics psilocybin Hallucinogens Antidepressants ssris Lexapro Big five
Citations 38
Key findings Both psilocybin therapy and escitalopram were associated with personality changes in a direction consistent with improved mental health, with no significant between-condition differences, except that pre-trial positive expectancy moderated post-escitalopram but not post-psilocybin personality changes.

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.

Comparable studies

Other randomized controlled trials on psilocybin for depression, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression 2021 Randomized controlled trial
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... 2020 Randomized controlled trial n = 24
Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. Adults with treatment-resistant depression 2022 Phase 2 double-blind randomized controlled trial n = 233

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