The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial.
Jessica S. Henry, Bruna Giribaldi, David Nutt, David Erritzøe, Robin Carhart-Harris, Taylor Lyons
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology June 23, 2025 DOI: 10.1016/j.euroneuro.2025.06.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 59 |
| Population | Patients with Major Depressive Disorder |
| Interventions | Psilocybin therapy Escitalopram |
| Dose | two high-dose sessions |
| Duration | 6-week intervention, 6-week follow-up |
| Topics | Depression Psilocybin |
| Keywords | Escitalopram Depression treatment Medication Condition Patients Improved attitudes Positive impact Psilocybin therapy Optimism Dysfunctional attitudes Pessimism Achievement Cognitive bias Pessimistic views Negative biases Dependency Self-control |
| Citations | 2 |
| Key findings | Psilocybin therapy produced large increases in optimism and improvements across all three domains of dysfunctional attitudes, whereas escitalopram improved only the achievement domain and did not change optimism. |
Abstract
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. 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. 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). 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.
Comparable studies
Other randomized controlled trials on psilocybin for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
| Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. Adults with treatment-resistant depression | 2022 | Phase 2 double-blind randomized controlled trial | n = 233 |