Sex-related differences in outcomes following psilocybin or escitalopram: a Bayesian secondary analysis

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.