Sex-Specific Effects of Psilocybin Versus Escitalopram on Anxiety and Anhedonia: A Bayesian Reanalysis of Antidepressant Treatment Outcomes
Aline Frick, Grace Blest‐hopley, Manesh Grin, David Erritzøe, David Nutt, Robin Carhart-Harris
Research Square June 19, 2026 preprint DOI: 10.21203/rs.3.rs-9880403/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind |
|---|---|
| Population | Adults with moderate-to-severe major depressive disorder |
| Interventions | Psilocybin Escitalopram |
| Duration | Six-week |
| Topics | Anxiety Depression Psilocybin Serotonin |
| Keywords | Escitalopram Anhedonia Randomized controlled trial Antidepressant Imipramine Clinical psychology Depressive symptoms Depression economics Clinical trial Sexual dysfunction |
| Key findings | Women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men. |
Abstract
Abstract
Rationale: Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, women remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined.
Objectives: This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple psychological domains.
Methods: We reanalyzed data from a six-week, double-blind randomized controlled trial comparing psilocybin with escitalopram in adults with moderate-to-severe MDD. Post-treatment depressive symptoms (MADRS, QIDS-SR-16, BDI), anhedonia (SHAPS), anxiety (STAI), thought suppression (WBSI), and well-being (WEMWBS) were modeled as a function of sex, treatment condition, their interaction, and baseline symptom severity. Sexual dysfunction severity (PRSexDQ-SALSEX), assessed only at the six-week follow-up, was analyzed separately as an ordinal outcome.
Results: Sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men (STAI: 95% CrI − 17.5 to − 3.29), whereas women receiving escitalopram showed greater reductions in anhedonia than men (SHAPS: 95% CrI − 4.63 to 0.00). For the remaining continuous outcomes, sex differences were generally small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, although the treatment-by-sex interaction was not significant.
Conclusions: This reanalysis identified domain-specific sex-related patterns in anxiety and anhedonia, suggesting that responses to psilocybin and escitalopram may differ between women and men. These preliminary findings support adequately powered, sex-balanced, and hormone-informed trials of serotonergic treatments for MDD.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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In a Bayesian reanalysis, women receiving psilocybin showed greater reductions in anxiety than men, while women receiving escitalopram showed greater reductions in anhedonia than men.
Synthesized
Comparable studies
Other randomized controlled trials on psilocybin for anxiety, most cited first.