Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPsilocybinCompleted

Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms

Randomised double-blind Phase II trial (n=59) comparing psilocybin versus escitalopram for major depressive disorder, assessing efficacy and mechanisms.

Target Enrollment
59 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind, parallel-group study comparing psilocybin dosing days with daily escitalopram or placebo over a 6-week comparator period in adults with moderate-to-severe major depressive disorder.

Outcomes include clinical depression measures and mechanistic investigations (neuroimaging and related biomarkers); eligibility required HAM-D ≥17 and excluded current or familial psychotic disorders and significant medical contraindications.

Study Arms & Interventions

Psilocybin + placebo

experimental

Psilocybin dosing with daily placebo for comparator period.

Interventions

  • Psilocybin
    via Oral• multiple dosing days

    Psilocybin administered on dosing days; daily placebo for 6 weeks.

Psilocybin + escitalopram

active comparator

Psilocybin dosing with daily escitalopram for comparator period.

Interventions

  • Psilocybin
    via Oral• multiple dosing days

    Psilocybin administered on dosing days.

  • Compound
    via Oral• daily

    Escitalopram daily for 6 weeks (active comparator).

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Major depressive disorder (DSM-IV)
  • 2. Depression of moderate to severe degree (17+ on the 17-item Hamilton Depression Scale (HAM-D)).
  • 3. No Magnetic Resonance Imaging (MRI) contraindications
  • 4. No SSRI contraindications
  • 5. Has a general practitioner (GP) or other mental healthcare professional who can confirm diagnosis
  • 6. 18-80 years of age
  • 7. Males and females
  • 8. Sufficiently competent with English language

Exclusion Criteria

  • Key exclusion criteria:
  • 1. Current or previously diagnosed psychotic disorder
  • 2. Immediate family member with a diagnosed psychotic disorder
  • 3. Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure e.g. creatine clearance:renal clearance (CLRC) < 30 ml/min etc.)
  • 4. History of serious suicide attempts requiring hospitalisation.
  • 5. Significant history of mania (determined by study psychiatrist and medical records)
  • 6. Psychiatric condition judged to be incompatible with establishment of rapport with therapy team and/or safe exposure to psilocybin, e.g. borderline personality disorder
  • 7. Blood or needle phobia
  • 8. Positive pregnancy test at screening or during the study, women who are planning a pregnancy and/or women who are nursing/breastfeeding.
  • 9. Participants who do not agree to use an acceptable contraceptive method throughout their participation in study.
  • 10. Current drug or alcohol dependence
  • 11. No email access
  • 12. Use of contraindicated medication
  • 13. Patients presenting with abnormal QT interval prolongation at screening or with a history of this (QTc at screening above 440ms for men and above 470ms for women)

Study Details

Locations

Imperial College Hammersmith campus — London, United Kingdom

Related Publications

Open Accessindividual

A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression

This preprint (2022) reanalyses the data of a clinical trial in which the effects of psilocybin were compared to that of the SSRI escitalopram for major depressive disorder. Bayesian secondary found indeterminate evidence that psilocybin is superior that escitalopram using the QIDS SR-16 while strong evidence favoured psilocybin when using the BDI-1D and MADRS and extremely strong evidence when using the HAMD-17. The results support the idea that psilocybin outperformed escitalopram but was not clinically meaningful and, psilocybin is almost certainly non-inferior to escitalopram.

Published
Journal
Psyarxiv
Authors
Bari, B. A., Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Nayak, S., Nutt, D. J., Peill, J. M., Rosas, F. E., Spriggs, M. J., Yaden, D. B.
Open Accessindividual

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

This 6-month follow-up of a Phase II, double-blind, randomised controlled trial (n=59) finds sustained improvements in depressive symptoms for both psilocybin therapy (PT) and escitalopram treatment (ET) for moderate-to-severe major depressive disorder (MDD). PT shows greater improvements in psychosocial functioning, meaning in life, and psychological connectedness compared to ET at the 6-month follow-up.

Published
Journal
EClinicalMedicine
Authors
Baker-Jones, M., Barba, T., Carhart-Harris, R. L., Erritzoe, D., Giribaldi, B., Greenway, K. T., Martell, J., Murphy-Beiner, A., Murphy, R., Nutt, D. J., Timmermann, C., Weiss, B.

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