Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Summary

This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in 'magic mushrooms', with the selective serotonin reuptake inhibitor (SSRI) escitalopram for major depressive disorder (MDD).

Timeline

Start

2019-01-07

Primary completion

2020-04-17

Completion

2020-10-17

Publications

• Background Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8.
• Results Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021 Apr 15;384(15):1402-1411. doi: 10.1056/NEJMoa2032994.
• Erritzoe D, Barba T, Greenway KT, Murphy R, Martell J, Giribaldi B, Timmermann C, Murphy-Beiner A, Jones MB, Nutt D, Weiss B, Carhart-Harris R. Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. EClinicalMedicine. 2024 Sep 21;76:102799. doi: 10.1016/j.eclinm.2024.102799. eCollection 2024 Oct.
• Peill J, Marguilho M, Erritzoe D, Barba T, Greenway KT, Rosas F, Timmermann C, Carhart-Harris R. Psychedelics and the 'inner healer': Myth or mechanism? J Psychopharmacol. 2024 May;38(5):417-424. doi: 10.1177/02698811241239206. Epub 2024 Apr 12.
• Szigeti B, Weiss B, Rosas FE, Erritzoe D, Nutt D, Carhart-Harris R. Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression. Psychol Med. 2024 Jun;54(8):1717-1724. doi: 10.1017/S0033291723003653. Epub 2024 Jan 22.
• Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas FE, Peill JM, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris R. A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression. Psychedelic Med (New Rochelle). 2023 Mar;1(1):18-26. doi: 10.1089/psymed.2022.0002. Epub 2022 Oct 28.
• Murphy R, Kettner H, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker-Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris R. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression. Front Pharmacol. 2022 Mar 31;12:788155. doi: 10.3389/fphar.2021.788155. eCollection 2021.
• Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R. Increased global integration in the brain after psilocybin therapy for depression. Nat Med. 2022 Apr;28(4):844-851. doi: 10.1038/s41591-022-01744-z. Epub 2022 Apr 11.

Drugs

Indications