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Psychedelics & Consciousness

Trial of Psilocybin versus Escitalopram for Depression

Carhart-Harris et al. · 2021 · New England Journal of Medicine

Head-to-head Phase 2 trial comparing psilocybin-assisted therapy with a standard SSRI in moderate-to-severe depression.

Research objective

Test whether two doses of psilocybin combined with psychological support are non-inferior to six weeks of daily escitalopram on the primary depression measure.

Methodology

Randomized double-blind controlled trial in 59 patients. Psilocybin arm: 25 mg x 2, three weeks apart, with preparation, dosing, and integration sessions. Escitalopram arm: 10–20 mg daily plus identical psychological support. Primary outcome: QIDS-SR-16 at week 6.

Key findings

  • No statistically significant difference on the primary QIDS-SR-16 outcome.
  • Psilocybin outperformed escitalopram on multiple secondary measures (response, remission, BDI-1A, work and social adjustment).
  • Adverse-event profile was favorable for psilocybin; functional unblinding was substantial.

Strengths

  • First rigorous head-to-head comparison of a psychedelic with an active antidepressant.
  • Comprehensive secondary outcome battery.

Limitations

  • Small sample, single site.
  • Functional unblinding limits inference about specific drug effect.
  • Patient population was relatively young and depression severity moderate.

Practical implications

  • Provided regulators and clinicians with the strongest head-to-head signal for psilocybin to date.
  • Helped catalyze multi-site Phase 3 programs.
Read the original paper

Related entities

Glossary · psilocybinGlossary · default-mode-networkGlossary · neuroplasticity

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