Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinNot yet recruiting

Treatment Resistant Depression Intervention with Psilocybin-assisted Psychotherapy

Open-label, non-randomised Phase I single-group study (n=20) testing psilocybin-assisted psychotherapy (initial 15 mg oral dose, up to 45 mg) for treatment-resistant depression in patients on stable psychotropic medication.

Target Enrollment
20 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

Open-label, single-group Phase I study of psilocybin-assisted psychotherapy in adults with treatment-resistant depression on stable psychotropic medication; initial dosing 15 mg oral with clinician-determined escalation to a maximum of 45 mg, 1–5 dosing sessions at least one week apart.

Therapy includes three preparation sessions and post-dose integration sessions; safety assessed via vitals (BP, heart rate, temperature) measured frequently during dosing and adverse event monitoring; mood outcomes assessed with MADRS (response ≥50% reduction; remission ≤10) with follow-up to 6 months.

Study Protocol

Preparation

3 sessions
60 min each

Dosing

5 sessions
480 min each

Integration

2 sessions
60 min each

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin-assisted psychotherapy

experimental

Open-label single-group psilocybin-assisted psychotherapy with flexible dosing (15–45 mg) and therapist-supported preparation and integration sessions.

Interventions

  • Psilocybin15 - 45 mg
    via Oral• 1–5 sessions• 5 doses total

    Initial 15 mg oral capsule; subsequent doses 15–45 mg per clinician assessment; sessions at least 1 week apart; supervised by therapy dyad for ~7–8 hours.

Participants

Ages
18 – 75
Sexes
Male & Female

Inclusion Criteria

  • Male and female participants 18 - 75 years of age.
  • Have given written informed consent.
  • Currently under the care of a psychiatrist who is able to provide a referral and willing to maintain ongoing oversight of their patient’s clinical care and treatment management throughout the duration of the study.
  • Have a DSM-5 diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode, as confirmed by the study psychiatrist.
  • Failed to clinically respond to at least two different classes of antidepressant medication treatment (despite adequate dose compliance and minimum treatment duration of 6 weeks) during the current major depressive episode. OR failed to respond to at least 75% of adequate trials of antidepressant medications in past episodes, including inadequate response to at least 2 different classes of antidepressants.
  • Have baseline MADRS score greater than or equal to 20.
  • Currently on psychotropic medication for depression (antidepressant and/or antipsychotic), and able to maintain stable psychotropic medications (including stable dose) from time of first psilocybin dose to last psilocybin dose, and at a dose not exceeding the recommended upper dose limit according to the Australian Medicines Handbook.
  • Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least 4 weeks prior to screening and is expected to remain stable until the final dose of psilocybin.
  • Will have accompanied transport home after treatment sessions and availability of a friend or family member and home-like environment for the 24 hours following psilocybin dosing.
  • Able to engage with psychotherapy.
  • Able to be followed up for entire duration of the study (i.e., planning to remain in Sydney for the duration of the study).
  • In good general medical health as confirmed by study doctor assessment supported with information from GP/referring psychiatrist.
  • Agree to refrain from using any alcoholic beverages or nicotine within 24 hours of each drug administration, and agree to refrain from caffeine for 2 hours before and 6 hours after each drug administration.
  • Agree to only take medications on the mornings of drug sessions that have been approved by the study psychiatrist.
  • Agree to refrain from taking any non-prescription drugs, nutritional supplements, or herbal supplements for one week before each psilocybin administration unless approved by the study psychiatrist.
  • Have none or limited lifetime use of hallucinogens (none in last 12 months).
  • Worked or studied in a context requiring some proficiency in spoken English (to ensure validity of neuropsychological testing).
  • Adequate clinical, ongoing support from own treating psychiatrist and other mental health clinicians, including safety plan in the event of becoming acutely suicidal, as determined by the study psychiatrist.

Exclusion Criteria

  • Women who are pregnant, intend to become pregnant during the study or who are currently nursing.
  • Have any significant cardiovascular conditions including uncontrolled hypertension (for the purposes of this study, hypertension is defined as (resting) systolic blood pressure >140 mmHg and/or (resting) diastolic blood pressure >90 mmHg).
  • Have epilepsy or a history of seizures.
  • Have history of any substance use disorder (except nicotine or caffeine) within the past 12 months.
  • Currently taking MAOIs, lithium or any other medication that may interfere with the study drug as determined by the study psychiatrist.
  • Current or lifetime history of meeting DSM-5 criteria for any psychotic disorders (including mood disorders with psychotic features), or bipolar I or II disorder.
  • Have a known first or second-degree relative with any psychotic disorder, or bipolar I or II disorder.
  • Significant suicide risk within the past year, as judged by study psychiatrist and informed by C-SSRS.
  • Have any condition preventing establishment of rapport and safe psilocybin treatment, as determined by the study psychiatrist.

Study Details

Locations

Unknown facility — Australia

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