Psilocybin Not Significantly Different from Escitalopram for Depression

By Kelly Young

Edited by Susan Sadoughi, MD

The psychedelic compound psilocybin did not differ significantly from the antidepressant escitalopram in its effect on symptoms of severe depression, according to a randomized, phase 2 trial in the New England Journal of Medicine.

Psychedelic compounds are thought to function through serotonin receptor (5-HT2A) agonism, a pathway linked to depression.

Researchers enrolled 59 adults with long-lasting, moderate-to-severe major depressive disorder who discontinued psychiatric medications and psychotherapy before the trial. Patients were randomized to receive either two doses of psilocybin (25 mg) or daily escitalopram over 6 weeks.

From baseline, the psilocybin group had an 8-point reduction in depression scores on a 27-point scale, compared with a reduction of 6 in the escitalopram group. However, the difference between groups was not statistically significant, and the authors note that the lack of a placebo group "limits conclusions about the effect of either agent alone." Psilocybin was associated with improvements in some secondary outcomes (e.g., 6-week depression remission) relative to escitalopram, but the authors caution that the confidence intervals weren't corrected for multiple comparisons. There were no serious adverse events reported.

An editorialist calls the study an "evidentiary milestone" but says "we are still awaiting definitive proof of the therapeutic efficacy of psychedelics and their capacity to improve the human condition."