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.


Background Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.

Aims To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.

Method Based on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.

Results A time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.

Conclusions These data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.”

Authors: Tommaso Barba, Sarah Buehler, Hannes Kettner, Caterina Radu, Bruna G. Cunha, David J. Nutt, David Erritzoe, Leor Roseman & Robin L. Carhart-Harris

Study details

Compounds studied

Topics studied

Study characteristics

59 Humans


Authors associated with this publication with profiles on Blossom

Hannes Kettner
Hannes Kettner is a Ph.D. student at the Imperial College Centre for Psychedelic Research and a Scientific Officer at MyDelica. He is interested in studying real-world psychedelic use, including ceremonies, retreats, burns, and what we can learn from them about creating a positive set & setting.

David Nutt
David John Nutt is a great advocate for looking at drugs and their harm objectively and scientifically. This got him dismissed as ACMD (Advisory Council on the Misuse of Drugs) chairman.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

David Erritzoe
David Erritzoe is the clinical director of the Centre for Psychedelic Research at Imperial College London. His work focuses on brain imaging (PET/(f)MRI).


Institutes associated with this publication

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

Linked Research Papers

Notable research papers that build on or are influenced by this paper

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.

Linked Clinical Trial

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).

PDF of Effects of psilocybin versus escitalopram on rumination and thought suppression in depression