A comparative assessment of the antidepressant efficacy of ketamine, psilocybin, and fluoxetine in a chronic stress model
Scientific Reports November 26, 2025 Małgorzata Domżalska, Joanna Kwiatkowska, Iwona Cichoń et al. 2 citations
In a mouse model of depression induced by chronic social defeat stress, a single dose of either ketamine or psilocybin reversed social avoidance within 24 hours, with effects lasting up to 14 days. In contrast, the SSRI fluoxetine showed no effect after a single dose or 7 days of repeated administration; antidepressant-like effects only appeared after 14 days of continuous treatment. These results mirror clinical patterns, where traditional SSRIs require weeks to work, while ketamine and psilocybin produce rapid and sustained effects. The findings highlight the potential of fast-acting agents as alternatives for treating major depressive disorder.