Psilocybin Versus Ketamine in Treatment-Resistant Depression

Last updated: May 16, 2022
Sponsor: National Institute of Mental Health, Czech Republic
Overall Status: Active - Recruiting

Phase

2

Condition

Depression

Treatment

N/A

Clinical Study ID

NCT05383313
PSIKET_001CZE
  • Ages 18-65
  • All Genders

Study Summary

The main goal is to compare the antidepressant effects of psilocybin and ketamine in patients with TRD versus the antidepressant inactive substance midazolam. The primary endpoint will be the antidepressant effect on the Montgomery- Asberg Depression Rating Scale (MADRS) 24 hours after treatment, the key secondary endpoints being the duration of antidepressant effect, the number of responses and remissions, and the time to standard antidepressant treatment during 3 months of observation. The exploratory part of the study aims to monitor changes in the functional brain states using simultaneous EEG / fMRI, before treatment versus 1 day and 1 week after. Based on literature data and recent data from healthy volunteers who participated in a previous study with psilocybin, the investigator will correlate antidepressant effects of drugs (using psychometric scales and reactions to emotionally salient stimuli (eye tracker)) with entropy and functional connectivity measures. Finally the investigator will explore the role of plasmatic neurobiological biomarkers in depression (BDNF, prolactin, ACTH and oxytocin).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Men and women aged 18-65
  2. Diagnosis of moderate to severe depressive disorder without psychotic symptoms -ICD-10 criteria F32.1-2 or F33.1-2 and at the same time MADRS score > 20
  3. The duration of the current depressive episode is at least 3 months and maximum 2years
  4. Treatment-resistant depression defined as:
  5. Failure of at least 2 and at most 4 adequate treatments (6 weeks of fulltherapeutic dose of antidepressant or adequate non-pharmacological treatment -e.g. psychotherapy, neurostimulation treatment, phototherapy, etc.) within thecurrent depressive episode, using at least 2 types of antidepressants withdifferent pharmacological mechanisms of action (augmentation is taken as a secondtreatment) or
  6. Intolerance of 2 different treatments and 1 adequate treatment or
  7. Intolerance of 3 different antidepressant treatments.
  8. Ability to understand the study protocol and to be able to complete all study visitsand examinations as defined per protocol.
  9. Participants in a clinical trial of childbearing potential must agree to the use ofprescribed contraceptive methods for the duration of the study

Exclusion

Exclusion Criteria:

  1. Severe psychiatric comorbidity (axis I MINI, ICD-10 F0.X - F99.X, the intensity of thedisorder will be clinically assessed by the study clinician)
  2. The current depressive phase is severe with psychotic symptoms (ICD-10: F32.3, F33.3)
  3. MADRS suicidality score (item 10)> 4
  4. Duration of the current depressive episode longer than 2 years
  5. Current drug or alcohol dependence (ICD-10: F17.x) with the exception of tobacco andwith the exception of abstinence lasting more than 2 years
  6. Claustrophobia, inability to undergo MR examination
  7. Pregnancy or breast-feeding or plan to become pregnant within the next 12 months
  8. Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP> 150/100 mmHg)
  9. Condition after stroke, myocardial infarction in the last 6 months
  10. Heart failure
  11. Untreated or decompensated hyperthyroidism
  12. Glaucoma
  13. Severe respiratory failure or acute respiratory depression
  14. History of seizures
  15. Other serious somatic disease or any other circumstance in which a significantincrease in blood pressure would pose a serious threat to health (to be assessed bythe study clinician)
  16. Pacemaker
  17. Metal implants made of MR incompatible materials
  18. Regular use of medication that could interact with psilocybin (to be assessed by theinvestigator)
  19. Regular use of antipsychotics with 5-HT2A receptor antagonist activity ordiscontinuation of their use for less than 14 days (eg risperidone, olanzapine,clozapine, quetiapine, ziprasidone)
  20. Current use of monoamine oxidase inhibitors (MAOIs)
  21. Previous experience with psilocybin, hallucinogenic mushrooms or ketamine is possiblein a maximum of 10% of patients. This experience must not be during the last 12 monthsor during the current depressive episode.
  22. Recent use of antidepressants with a direct antagonistic effect on 5-HT2A receptorssuch as SARI and tetracyclic antidepressants (eg trazodone, mirtazapine, mianserin) ordiscontinuation of their use for less than 14 days
  23. Electroconvulsive therapy in the previous 3 months
  24. Daily use of benzodiazepine anxiolytics higher than the equivalent of 10 mg diazepam
  25. Allergy to any of the components of study drugs

Study Design

Total Participants: 60
Study Start date:
May 01, 2021
Estimated Completion Date:
April 30, 2025

Study Description

The main aim of the study is to verify the efficacy and safety of a single dose of psilocybin 20 mg in the treatment of TRD in adults in a randomized clinical trial with active comparator ketamine 200 mg (rapid onset acting antidepressant) and negative control midazolam 5 mg (drug with no antidepressant properties). Primary objective: 1) verification of the rapid antidepressant effect of psilocybin compared to ketamine using the MADRS scale at 24 hours. Secondary objectives: 1) on days 3, 7 and 14 and 3, 4, 5, 6, 8 and 12 weeks after application of the substances, evaluate / compare: a) the duration of effects of both substances using the MADRS scale b) antidepressant effects according to the subjective evaluation of patients

  • QIDS scale. c) response rate (50% reduction on the MADRS scale) and remission (MADRS ? 10).
  1. time to return of depressive symptoms defined according to the criteria for the use of antidepressants within 12 weeks 3) safety profile of study medication Exploratory objectives:
  2. Evaluate the antidepressant effect depending on: a) the intensity of acute psychological effects assessed using the subjective scale of 5D-ASCs and the objective scale of BPRS, b) depending on the retrospective assessment of persistent effects using the Persisting effects scale, c) the degree of eye contact with negative and neutral emotion faces measured by eye-tracking before and after treatment (on days 1 and 7). 2) To evaluate the neurobiology of the antidepressant effect in relation to: a) plasma levels of the major metabolite of psilocin, markers of neuroplasticity, antidepressant effect and stress (BDNF, prolactin, oxytocin, ACTH) at 90 min, 3, and 6 h after administration of study medication compared to pre-administration levels, b) changes in resting-state brain activity (connectivity, entropy) measured by simultaneous EEG / fMRI functional imaging methods before and after 1 and 7 days after treatment.

Connect with a study center

  • National Institute of Mental Health

    Klecany, 250 67
    Czechia

    Active - Recruiting

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