Feasibility and Tolerability of Daily Theta Burst Stimulation in Autistic Youth with Intellectual Disabilities and Minimally Speaking Status: A Pilot Double-Blind Randomized Sham-Controlled Trial.

Scarce clinical trials involving autistic people with intellectual disability (ID) and minimally speaking (MS) status have been a substantial unmet research need in the field. Although earlier studies have demonstrated the feasibility and beneficial potentials of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in intellectually able autistic people, the feasibility and tolerability of applying rTMS in autistic people with ID/MS has never been studied. We conducted the world-first 4-week randomized, double-blind, sham-controlled pilot trial to investigate the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS) over the left DLPFC in autistic youth with ID/MS. 25 autistic youth with ID/MS (aged 8-30 years) were randomized to a 20-session 4-week daily iTBS (n = 13) vs. sham stimulation (n = 12) with follow-up 4 and 8 weeks, respectively, after the last stimulation. A retention rate was 100% in our study. Adverse events of local pain (38%) and dizziness (8%) were only noted in the active group. All adverse events were mild and transient. There were no seizures, new behavioral problems, or other severe/serious adverse events noted. No participants dropped out due to adverse events. With a small sample size, we did not find any beneficial signal of DLPFC iTBS. Our pilot data suggest regular daily TBS treatment for four weeks is feasible, well tolerated and safe in autistic youth with ID/MS. Future randomized controlled trials with sufficiently powered samples are needed to investigate the beneficial potential of rTMS/TBS for autistic people with ID/MS.