Across clinical trials published between 2023 and 2025, psilocybin consistently produced large and sustained reductions in depressive symptoms, with response rates commonly exceeding 40% after one or two supervised sessions. By comparison, esketamine trials showed remission rates closer to 25–30% with repeated dosing, while newer oral agents required daily use to maintain effects. Framed alongside these options, psilocybin stands out for delivering durable benefit with minimal dosing frequency, reshaping how psychiatry weighs intensity versus continuity in depression care.