Does psilocybin work better than antidepressants like escitalopram?

The best-known direct comparison does not establish that psilocybin is better. Carhart-Harris and colleagues randomized 59 people with depression to a psilocybin treatment program or daily escitalopram, with psychological support in both groups. At six weeks, the groups did not differ significantly on the prespecified primary depression questionnaire. Some secondary outcomes favored psilocybin, but those analyses were not adjusted for the number of comparisons. They are encouraging signals rather than a basis for declaring psilocybin the superior antidepressant.[1]

A nonsignificant difference also does not prove that the treatments are equally effective. This was a small, short study, and recognizable psychedelic effects make blinding difficult. The practical comparison includes the intensity of supported sessions, tolerability, maintenance needs and which patients were eligible, not just whether one treatment involves fewer dosing days. A six-month follow-up was observational, and many participants received additional interventions, making it harder to attribute later outcomes to the original assignment alone. The findings are not a reason to stop a prescribed antidepressant without a clinician-guided plan.[1][2]