Attention-Deficit/Hyperactivity Disorder (ADHD) is estimated to affect up to 9.5% of school-aged children and 4.4% of adults. ADHD is associated with increased functional impairments, comorbid psychopathology, and overall health care costs. Although various psychosocial interventions are employed, medication remains the mainstay of ADHD treatment. It is estimated that over 2.8 million children in the United States are prescribed psychostimulants, mostly for ADHD. Although these are generally safe and effective in acute treatment, considerable concerns remain about side effects and the absence of demonstrated long-term benefit. Parents are highly ambivalent about using ADHD medications. While there is great demand for non- medication approaches to ADHD, most popular alternatives are not linked to any mechanistic understanding of brain processes and similarly lack significant scientific evidence to support their use. External trigeminal nerve stimulation (eTNS) is a non-invasive method of brain modulation with demonstrated success in treating adults with medication-resistant epilepsy and depression. In eTNS, the trigeminal nerve receives low current electrical stimulation via an electrode applied to the forehead and worn during sleep. Preliminary adult studies revealed significant improvements in mood, sleep, and attention. PET imaging demonstrated acute eTNS-related activation in brain areas involved in attention and executive functioning. A preliminary pediatric study based on this work assessed the feasibility of eTNS for ADHD. Results demonstrated that eTNS was well tolerated and accepted, and was associated with significant improvements in ADHD symptoms and laboratory measures of response inhibition and working memory. This R34 proposes a three-year clinical trial development project to further standardize eTNS in preparation for definitive ADHD efficacy trials and to elucidate underlying brain mechanisms that will potentially support use of eTNS in ADHD as well as other behavioral, emotional, and cognitive disorders. The project is a four-week double-blind randomized trial of active vs. sham eTNS followed by four weeks follow-up after treatment discontinuation. Participants will have repeated assessments on behavioral ratings, cognitive processes, and cortical activation via electroencephalography (EEG). This study will assess differences in outcome trajectories by condition in the first randomized controlled trial of eTNS for ADHD, validity and fidelity of sham eTNS as a blinded control, time course effects regarding onset and offset of response, and underlying mechanisms of brain change that are associated with treatment outcomes. The proposal is consistent with several NIMH priorities, including the development of innovative interventions and designs for intervention studies, development of an integrated understanding of brain disorder processes that provide the foundation for understanding mental disorders, and assessment of the mechanisms of action of efficacious interventions in the brain.
This study addresses the mission of the NIMH in supporting the development of an innovative treatment intervention for a commonly occurring behavioral disorder, expanding our understanding of brain processes as they relate to behavior and cognition, and by assessing the mechanisms of action underlying brain change. The proposed project is a four-week double-blind randomized trial of active vs. sham external trigeminal nerve stimulation (eTNS) for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), during which participants will have repeated assessments on behavioral ratings, cognitive processes, and cortical activation via electroencephalography (EEG). Information derived will provide a basis for definitive controlled clinical efficacy trials of eTNS as a non-medication intervention fr ADHD, and will potentially identify mechanisms of brain response that could prove useful in the treatment of other ADHD and other behavioral, cognitive, and emotional disorders.