Psilocybin rTMS for Treatment Resistant Depression
Phase II, randomised 2x2 factorial study (n=100) testing COMP360 psilocybin (25 mg vs 1 mg) combined with active or sham accelerated iTBS (SAINT/SNT) in treatment-resistant MDD.
Details
This phase II, randomized 2x2 factorial trial (device × dose) will enroll 100 participants with treatment-resistant major depressive disorder to evaluate safety, feasibility, and efficacy of sequencing COMP360 psilocybin therapy with accelerated intermittent theta burst stimulation (aiTBS/SAINT).
Participants receive psychological preparation (two sessions), a single psilocybin dosing session (~6–8 hours) with integration sessions, followed the next week by either active aiTBS (10 sessions/day for 5 days) or sham aiTBS. Neurobiological assessments (fMRI, EEG) occur at baseline, 2 days post-psilocybin, and ~14 days post-psilocybin/after aiTBS.
Primary aims are to determine safety and feasibility of sequencing treatments and to test whether the combination demonstrates superior acute and sustained antidepressant effects; additional aims include examining neurobiological and inflammatory biomarker changes and moderators of response.