Actively Recruiting
Assessing the Safety, Tolerability, and Efficacy of Psilocybin Therapy Followed by Accelerated Intermittent Theta Burst (aiTBS) rTMS for Treatment-Resistant Major Depressive Disorder
Led by University of Texas at Austin · Updated on 2025-11-26
100
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying the safety and feasibility of combining psilocybin therapy with a short course of accelerated intermittent theta burst stimulation (aiTBS) in adults with treatment-resistant major depressive disorder (MDD). This phase II clinical trial aims to evaluate whether this combination offers benefits beyond either treatment alone and to observe related neurobiological changes and effects on blood inflammation markers. The study involves 100 participants aged 22 to 65 who have moderate to severe depression not responsive to standard treatments. Participants are randomly assigned to one of four groups receiving either a full 25mg dose or a low 1mg dose of psilocybin, followed by either active aiTBS treatment known as Stanford Neuromodulation Therapy (SNT) or a sham procedure. Psilocybin therapy includes preparation sessions, a dosing day lasting 6 to 8 hours, and integration sessions over five consecutive days. The following week involves daily aiTBS sessions lasting about 10 hours per day for five days. Clinical and brain imaging assessments take place at baseline, after psilocybin, and following aiTBS treatment. Throughout participation, individuals undergo detailed clinical assessments, functional magnetic resonance imaging (fMRI), and electroencephalographic (EEG) recordings to measure brain activity and connectivity. These assessments are repeated 1 to 2 weeks after treatments and at multiple follow-up points up to 12 months to track depression symptoms, quality of life, anxiety, and other mood-related measures. Safety and tolerability are closely monitored. The total study duration per participant includes screening, treatment over three weeks, and long-term follow-up over one year.
CONDITIONS
Brief Title
Psilocybin rTMS for Treatment Resistant Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 22 to 65 years
- Able to understand and communicate in English
- Current major depressive episode lasting at least 3 months
- Moderate to severe depression with a MADRS score of 20 or greater
- Treatment-resistant depression defined by failure of two or more adequate antidepressant treatments
- Willing and able to attend daily visits and participate in all study procedures
- Willing to discontinue certain antidepressant or augmenting medications and remain off them during the study period
You will not qualify if you...
- History or current diagnosis of psychotic disorder, bipolar disorder, or personality disorder
- Current diagnosis of PTSD, OCD, eating disorders, or substance-use disorder
- Alcohol or substance-use disorder within the past year
- Previous rTMS treatment or certain brain stimulation therapies during current episode
- Participation in active psychotherapy for depression unless stable supportive therapy
- Significant suicide risk in the past year or at screening
- Depression caused by medication or medical condition
- Major medical or behavioral factors interfering with participation
- Recent or excessive use of serotonergic psychedelics
- Presence of ferrous metal implants or medical devices incompatible with rTMS or MRI
- History of seizures, epilepsy, neurological disorders, or significant head injury
- Pregnancy, nursing, or inadequate contraception
- Severe claustrophobia or uncontrolled hypertension or thyroid disease
- Serious heart conditions or uncontrolled diabetes
- Positive drug screening for abuse substances
- Abnormal clinical test results at screening
- Participation in another interventional study within 6 months
- Known hypersensitivity to psilocybin or similar psychedelics
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for clinical and neurobiological assessments including fMRI and EEG recordings
Duration - 5 days
Participants undergo psilocybin therapy involving preparation sessions, a dosing session, integration sessions, and post-dosing assessments over five consecutive days.
Daily visits including 2 preparation sessions (~1.5-2 hours each), 1 dosing session (~6-8 hours), and 2 integration/post-dosing sessions (~1 hour each)
Duration - 5 days
Participants receive accelerated intermittent theta burst (aiTBS) rTMS treatment or sham treatment delivered over 10 sessions daily for 5 consecutive days targeting personalized brain regions.
Daily visits with 10 sessions per day lasting 10 hours total
Duration - 12 months
Participants complete post-treatment clinical and neurobiological assessments and undergo long-term follow-up clinical assessments to monitor treatment response and potential relapse.
Visits at 1, 2, 3, 4, 6, 9, and 12 months post-treatment start
Trial Site Locations
Total: 1 location
1
Health Discovery Building (HDB), 1601 Trinity St., Bldg B., Z0600
Austin, Texas, United States, 78712
Actively Recruiting
Research Team
L
Lauren K Enten, B.S.A.
G
Gregory A Fonzo, Ph.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
FACTORIAL
Primary Purpose
TREATMENT
Number of Arms
4
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