Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression
Molecular Psychiatry February 18, 2026 Marie Huc, Sara Siddiqi, Mysa Myers et al. 1 citation
Esketamine, a fast-acting antidepressant, improves depression in both sexes among adults with treatment-resistant depression. However, females showed greater overall improvement and higher odds of treatment response than males toward the end of four-week trials, regardless of whether they received esketamine or placebo. Females also experienced more pronounced reductions in sadness, detachment, and neurovegetative symptoms at certain time points. In contrast, males showed a significant reduction in sadness symptoms two days after esketamine. These findings indicate that sex assigned at birth influences the trajectory and symptom profile of antidepressant response, highlighting its importance for personalized treatment strategies.