Psilocybin and escitalopram similarly reduce negative emotional bias in depression, despite different effects on the brain

A randomized six-week trial of 59 people with moderate-to-severe depression found that psilocybin and the SSRI escitalopram both reduced a negative bias in facial-expression recognition. Before treatment, participants were more likely to misinterpret ambiguous or positive faces as negative; after treatment, both groups made fewer negative misclassifications and responded more quickly to emotional cues. The behavioral results were similar even though earlier imaging showed different brain effects: escitalopram reduced amygdala activity, while psilocybin did not. The reduction in bias did not correspond to lower depression scores at six weeks. At ten weeks, however, improvement in positive-face recognition predicted lower depression scores among escitalopram recipients, not those who received psilocybin, suggesting that the treatments may share an outcome while relying on different mechanisms or timelines. Interpretation is limited by the absence of a pure inactive control group, possible treatment-preference bias, and emotional testing only at baseline and six weeks.