Clinical trial NCT03429075: Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms
Official title: Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Keywords: depression
mdd
major depression
major depressive disorder
unipolar depression
psilocybin
psychedelics
psychedelic
escitalopram
ssri
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Alexander Mosely Charitable Trust
First posted: 2018-02-12
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility 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

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)

Primary outcomes:
measure: Percentage Change of the BOLD Signal
timeFrame: Baseline measure vs 6 weeks post 1st psilocybin dosing
measure: Change in QIDS-16: Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-16)
timeFrame: Baseline vs 6 weeks post 1st psilocybin dosing
Secondary outcomes:
measure: Change in Hamilton Depression Scale (HAMD-17)
timeFrame: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose
measure: Change in Beck Depression Inventory (BDI-IA)
timeFrame: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose
measure: Change in MADRS
timeFrame: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose
measure: Number of Patients Who "Responded": Quick Inventory of Depressive Symptomatology (QIDS-16) Response at 6 Weeks
timeFrame: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose
measure: Number of Patients Who "Remitted": QIDS-16 Remission Rate
timeFrame: Change from baseline (7-10 days pre-dosing) to 6 weeks after the first psilocybin dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Hammersmith campus
Study officials:
affiliation: Imperial College London
name: David J Nutt, Medicine
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.