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Fast and sustained effect of 2 administrations of psilocybin on depression

Presented by
Dr David Erritzoe, Imperial College London, UK
ECNP 2022
Phase 2, Psilodep-RCT
Psilocybin outperformed escitalopram in reducing symptoms of long-standing, moderate-to-severe major depressive disorder. The positive effects of 2 administrations of psilocybin were maintained for at least 6 months.

Open-label pilot studies have shown promising results for psilocybin-assisted therapy for depression [1]. Dr David Erritzoe (Imperial College London, UK) presented long-term results from the double-blind, randomised-controlled, phase 2 Psilodep-RCT trial (NCT03429075), which compared 6 weeks of daily escitalopram versus 2 treatment sessions with psilocybin in 59 patients with moderate-to-severe major depressive disorder [2]. The initial trial results favoured psilocybin over escitalopram by both decreasing symptoms (Quick Inventory of Depressive Symptomatology [QIDS]-16 score) and increasing well-being (Warwick-Edinburgh Mental Well Being Scale) of participants after 6 weeks [3]. The emission rate at week 6 was 57.1% in the psilocybin arm versus 29.1% in the escitalopram arm. Moreover, a significant improvement in QIDS-score was already observed in week 1.

Follow-up data showed that the antidepressant effect of psilocybin was maintained for at least 6 months [2]. In addition, in contrast to participants in the escitalopram arm, participants in the psilocybin arm demonstrated a significant decrease in rumination and thought suppression. This decrease positively correlated with the degree of ego dissolution and psychological insight reported after the psilocybin dosing session, said Dr Erritzoe.

Analyses of functional MRI recorded at baseline and 3 weeks after the second psilocybin dose showed an expansion of global connectivity, which was reflected in a decrease of network modularity and correlated with treatment outcome. This change in modularity was not seen after treatment with escitalopram [4]. “Our findings suggest that psilocybin and escitalopram differ in psychological outcomes as well as in biological consequences,” concluded Dr Erritzoe.

  1. Carhart-Harris RL, et al. Lancet Psychiatry. 2016;3:619–627.
  2. Erritzoe D, et al. Psychedelic Therapy; clinical outcomes and mechanisms from depression trial with psilocybin. Abstract S03.01, ECNP Congress 2022, 15–18 October, Vienna, Austria.
  3. Carhart-Harris RL, et al. N Eng J Med. 2021;384:1402–1411.
  4. Daws RE, et al. Nat Medicine. 2022;28:844–851.


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