Sex-related differences in outcomes following psilocybin or escitalopram: a Bayesian secondary analysis.
Aline Frick, Grace Blest‐hopley, Manesh Girn, David Erritzøe, David Nutt, Robin Carhart-Harris
Psychopharmacology October 26, 2026 DOI: 10.1007/s00213-026-07177-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc Bayesian reanalysis of a randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 59 |
| Population | Adults with moderate-to-severe major depressive disorder (20 female; psilocybin n=30, 11 female; escitalopram n=29, 9 female) |
| Interventions | Psilocybin Escitalopram |
| Duration | Six-week trial |
| Measures | STAI |
| Topics | Anxiety Depression Psilocybin |
| Keywords | Anhedonia Bayesian analysis Escitalopram Sex differences |
| Key findings | No outcome showed an overall sex difference across treatments. Within psilocybin, females had lower post-treatment anxiety than males (STAI adjusted difference -8.77, 95% CrI -15.73 to -1.73), though the estimate varied across priors and the narrowest prior included zero; the sex-by-treatment interaction was inconclusive. Among males, sexual dysfunction was lower with psilocybin than escitalopram, and within escitalopram females reported less sexual dysfunction than males. |
Abstract
Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, females remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple psychological domains. We conducted a post hoc Bayesian analysis of a six-week, double-blind trial in adults with moderate-to-severe MDD (N = 59; 20 female; psilocybin n = 30, 11 female; escitalopram n = 29, 9 female). Post-treatment depression, anhedonia, anxiety, thought suppression, and well-being were modeled by sex, treatment, sex-by-treatment interaction, and baseline score. Sexual dysfunction, measured post-treatment only, was analyzed ordinally. Prior-sensitivity analyses used narrower and wider priors. No outcome showed an overall sex difference across treatments. Within psilocybin, females had lower post-treatment anxiety than males (STAI adjusted difference = -8.77, 95% CrI = -15.73 to -1.73; BFany = 11.18), although the estimate varied across priors and the narrowest prior included zero. The sex-by-treatment interaction was inconclusive (difference=-8.62, 95% CrI=-18.36 to 1.30; BFany = 2.55). A directional female advantage in anhedonia with escitalopram was unsupported by Bayes factors. No sex differences emerged on depression scales. Among males, sexual dysfunction was lower with psilocybin than with escitalopram. Within escitalopram, females reported less sexual dysfunction than males. This reanalysis identified sex-related patterns in anxiety under psilocybin but no clear treatment-specific interaction. Findings support adequately powered, sex-balanced trials incorporating hormonal and reproductive factors.
Comparable studies
Other randomized controlled trials on psilocybin for anxiety, most cited first.