The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial

Background Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes and pessimism than healthy individuals and these biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in MDD. Methods Secondary analysis of a two-arm, randomized controlled trial ( ClinicalTrials.gov Identifier: NCT03429075 ) assessing the effect of psilocybin therapy versus escitalopram on ‘maladaptive’ cognitive biases relevant to the construct of depression. Psilocybin group participants received two 25mg doses and escitalopram group received three weeks of daily 10mg, increased to 20mg for a following three weeks. Primary outcomes in this analysis were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales. Findings Fifty-nine MDD patients were randomly allocated to the psilocybin (n=30) or escitalopram (n=29) groups. Self-reported optimism showed a large and significant increase six-weeks after psilocybin treatment ( M diff =6·63 p