Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in ‘magic mushrooms’, with the SSRI (selective serotonin reuptake inhibitor) escitalopram for major depressive disorder (MDD).

Status Completed
Results Published Yes
Start date 01 July 2019
End date 10 January 2020
Chance of happening 100%
Phase Phase II
Design Blinded
Type Interventional
Generation First
Participants 39
Sex All
Age 18- 80
Therapy No

Trial Details

This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in 'magic mushrooms', with the SSRI (selective serotonin reuptake inhibitor) escitalopram for major depressive disorder (MDD).

NCT Number NCT03429075

Sponsors & Collaborators

Imperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.

Alexander Mosley Charitable Trust
This company doesn't have a full profile yet, it is linked to a clinical trial.

Papers

Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression
This pre-print analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.

Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression
This reanalysis of an RCT (n=55) compared escitalopram and psilocybin (COMP360) for treating depression (MDD). Patients had higher expectancy for psilocybin, but only expectancy for escitalopram predicted therapeutic outcomes. Additionally, pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, suggesting psychedelic therapy may be less vulnerable to expectancy biases, and highly suggestible individuals may be primed for response to psilocybin treatment.

How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change
This re-analysis of the psilocybin (25mg) versus escitalopram (antidepressant, 6 weeks) RCT finds that in the psilocybin arm, experiential avoidance reductions led to improvements in mental health outcomes (e.g. depression severity). Note: the trial itself was insignificant on the primary measure of depression.

Body mass index (BMI) does not predict responses to psilocybin
This pooled analysis (n=77) of body mass index (BMI) data from three psilocybin (25mg) trials finds that BMI doesn't predict the intensity of the response to psilocybin. A fixed-dosing schedule (instead of dosage based on weight which is common for MDMA and ketamine) is probably best going forward in psilocybin-assisted trials.

Psychedelics and sexual functioning: a mixed-methods study
This mixed-methods study combines data from two studies, one large naturalistic study (n=261) and one smaller controlled clinical trial (n=59), to investigate the post-acute effects of psychedelics on self-reported sexual functioning. It finds that naturalistic use of psychedelics is associated with improvements in sexual pleasure, communication, satisfaction with one’s partner, and physical appearance. Similarly, a controlled trial comparing psilocybin therapy with the SSRI escitalopram for depression shows that patients treated with psilocybin report positive changes in sexual functioning, unlike those treated with escitalopram.

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression
This analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram on personality traits in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Significant decreases in neuroticism, introversion, disagreeableness, and impulsivity, and increases in absorption, conscientiousness, and openness were observed in the PAT group, while similar changes were seen in the escitalopram group.

Effects of psilocybin versus escitalopram on rumination and thought suppression in depression
This analysis (n=59) of the psilocybin vs escitalopram for depression study finds that those in the psilocybin arm of the study significantly decreased rumination. Only those who were in the psilocybin arm and responded (>50% symptom reduction) had reduced thought suppression (rumination was lower in both responder groups). Ego dissolution and psychological insight, for the psilocybin group, correlated with decreases in rumination and thought suppression.

Trial of Psilocybin versus Escitalopram for Depression
This double-blind placebo-controlled study (n=59) compared psilocybin (2x25mg; 3 weeks apart) to escitalopram (SSRI) over a six-week period and found large improvements in depression scores for those suffering from depression (MDD) in both groups. On the main measure of depression, the QIDS-SR-16, there was no significant difference between both groups. The study did find significant differences, favoring psilocybin, on the HAM-D-17, MADRS, avoidance, flourishing, wellbeing, and suicidality.

Measures Used

Quick Inventory of Depressive Symptomatology
The Quick Inventory of Depressive Symptomatology (Self-Report) (QIDS-SR16) is a self-report tool designed to screen for depression and measure changes in the severity of symptoms.

Data attribution

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