A lack of efficacy of continuous theta burst stimulation over the left dorsolateral prefrontal cortex in autism: A double blind randomized sham-controlled trial

Although previous open-label trials suggest the therapeutic potential of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in autism spectrum disorder (ASD), methodological caveats exist. We conducted an 8-week randomized, double-blind sham-controlled trial to investigate the efficacy of inhibitory continuous theta burst stimulation (cTBS, a variant of rTMS) over the left DLPFC in individuals with ASD. Sixty children, adolescents and young adults (aged 8-30 years) with ASD without co-occurring intellectual disabilities were randomized to a 16-session 8-week cTBS versus sham stimulation course, with a follow-up 4 weeks after the trial. The Active group was not superior to the Sham group in any clinical or neuropsychological metrics at Week 8 or Week 12. Time effects of 8-week cTBS on symptoms and executive function were remarkable in both Active and Sham groups, with comparable response rates and effect sizes of changes in symptoms/cognition between groups. Our results from a sufficiently powered sample do not endorse the superior efficacy of cTBS over the left DLPFC to the shamed stimulation for children, adolescents and adults with ASD. These findings suggest that earlier positive open-label trial findings may be generalized by generalized/placebo effects. This highlights the urgent need for more rTMS/TBS studies with rigorous trial designs in ASD.