Negative affective bias in depression following treatment with psilocybin or escitalopram – a secondary analysis from a randomized trial

Journal article

Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing. Patients with long-standing moderate-to-severe depression were randomly and double-blindly assigned in a 1:1 ratio to receive either 1) two doses of 25 mg of psilocybin, 3-weeks apart, plus 6-weeks of daily placebo (psilocybin group N = 30); or 2) two doses of 1 mg of psilocybin 3-weeks apart plus 6-weeks of daily oral escitalopram (escitalopram group N = 29); all patients received the same psychological support. Behavioural measures of affective bias as well as subjective measures of depression were collected at baseline and at the primary 6-week endpoint, using an established computerised task (Facial Emotion Recognition Task) and Quick Inventory of Depressive Symptomatology, respectively. Change in affective bias was further correlated with change in depression scores measured concurrently as well as at 1-month post-trial follow-up (week-10), corrected for baseline depression severity. Negative bias in facial expression recognition decreased after both treatments to a comparable level. Concurrently, change in negative affective bias was not associated with change in depression. Longitudinally, a decrease in the misclassification of positive faces as negative was associated with a decrease in depression scores at week-10 for the escitalopram group only. Therefore, a more positive behavioural bias in emotional processing was seen following psilocybin and citalopram compared to baseline. This highlights the potential for at least some overlap in cognitive mechanisms across two distinct treatments, which is noteworthy given the short dosing regimen with psilocybin.

Authors: Martens, MAG; Cunha, BG; Erritzoe, D; Nutt, D; Carhart-Harris, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Translational Psychiatry
• Volume: 15
• Issue: 1
• Article number: 502
• Publication date: 2025-11-13
• Acceptance date: 2025-10-08
• DOI: 10.1038/s41398-025-03693-w
• EISSN: 2158-3188
• ISSN: 2158-3188
• Language: English
• Keywords: Escitalopram; Citalopram; Depression (economics); Placebo; Randomized controlled trial; Psilocybin; Neuropsychology