Safety and Effectiveness of Psilocybin Therapy Combined with Accelerated Theta Burst rTMS for Treatment-Resistant Major Depression

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.

Psilocybin rTMS for Treatment Resistant Depression