The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial
Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Henry, J., Lyons, T., Nutt, D. J.
This secondary analysis of an RCT comparing psilocybin therapy to escitalopram in MDD patients (n=59) found that psilocybin produced superior improvements in cognitive biases. Psilocybin significantly increased self-reported optimism (d=1.1) and optimistic beliefs about desirable life events (d=1.1), while improving all three domains of dysfunctional attitudes (achievement, dependency, and self-control). Escitalopram showed more modest effects, reducing pessimism about negative events and improving only the achievement domain of dysfunctional attitudes.
Abstract
Background: Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes than healthy individuals and these pessimistic biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in depression.Methods: Secondary analysis of a two-arm randomized controlled trial assessing the effect of psilocybin therapy versus escitalopram on ‘maladaptive’ cognitive biases relevant to the construct of depression. Primary outcomes 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 increase six-weeks after psilocybin treatment (Mdiff=6⋅63 p < 0⋅0001; 95 % CI [4⋅06, 9⋅20], d = 1⋅1), whereas there was no change following escitalopram (Mdiff=1⋅52, p = 0⋅205; 95 % CI [-0⋅59, 3⋅62], d = 0⋅4). Behavioral results found that patients were more optimistic about desirable life events after psilocybin treatment (Mdiff=0⋅16, p = 0⋅0002; 95 % CI [0⋅08, 0⋅23], d = 1⋅1), but they were also less pessimistic about negative life events after escitalopram treatment (Mdiff=0⋅07, p = 0⋅018; 95 % CI [0⋅01, 0⋅13], d = 0⋅5). We found improvements in all three domains of dysfunctional attitudes following psilocybin treatment: achievement (Mdiff=10⋅37, p < 0⋅0001; 95 % CI [6⋅38, 14⋅53], d = 1⋅0); dependency (Mdiff=7⋅97, p < 0⋅0001; 95 % CI [4⋅00, 11⋅93], d = 0⋅9) and self-control (Mdiff=6⋅40, p = 0⋅0006; 95 % CI [2⋅60, 10⋅20], d = 0⋅8)), whereas only the achievement domain improved after escitalopram (Mdiff=4⋅10, p = 0⋅005; 95% CI [1⋅35, 6⋅86], d = 0⋅6).Interpretation: These results suggest that two high-dose sessions with psilocybin therapy are superior to a six-week daily course of a selective serotonin-reuptake inhibitor antidepressant, in remediating negative cognitive biases in depression.