A recent multicenter clinical trial led by King's College London has found that a device cleared by the US Food and Drug Administration (FDA) for treating Attention-Deficit/Hyperactivity Disorder (ADHD) does not reduce symptoms in children and adolescents. The study involved 150 participants between eight and 18 years old across two sites in London and Southampton.
The device, which uses trigeminal nerve stimulation (TNS), was cleared by the FDA in 2019 based on results from a smaller study involving 62 children. However, the earlier research did not include rigorous controls for placebo effects, raising concerns about its findings. In contrast, the new UK trial implemented a more robust placebo condition to assess the effectiveness of TNS.
Half of the participants received real TNS treatment nightly for four weeks, while the other half received a "sham" version with minimal stimulation designed to serve as a control. Both groups used battery-powered electrodes applied to their foreheads during sleep.
Professor Katya Rubia of King's College London commented on the importance of proper placebo controls in such trials: "Our study shows how important it is to design an appropriate placebo condition in clinical trials of brain therapies. There is a large placebo effect with high-tech brain therapies, in particular for patients and families that have an expectation that they can adjust brain differences associated with ADHD. It is hence paramount to control for placebo effects in modern brain therapies to avoid false hopes."
Researchers evaluated outcomes using parent-reported ADHD symptoms as well as objective measures of hyperactivity, attention, mood, anxiety, and sleep quality. The trial found no significant changes between those who received actual TNS therapy and those who had sham treatment. While most participants reported little or no burden from using the device and there were no serious adverse events, there was also no improvement in core ADHD symptoms or related behaviors.
Professor Samuele Cortese from University of Southampton emphasized the need for strong evidence when considering treatments: "Rigorous evidence, such as that generated by this study, is essential for supporting shared decision-making regarding interventions for ADHD. It empowers individuals with ADHD and their families to make informed choices about the treatment of ADHD. Clinicians, individuals with ADHD, and their families need to know which treatments work, and which do not based on the best evidence."
The research was funded by partnerships including the National Institute for Health Research (NIHR), UKRI Medical Research Council (MRC), Efficacy and Mechanism Evaluation Programme (EME), and NIHR Maudsley Biomedical Research Centre. Recruitment included several NHS trusts through Child and Adolescent Mental Health Services clinics.
Currently, stimulant medications are known to improve short-term symptoms in about 70% of those treated but questions remain regarding long-term effects. Non-invasive alternatives like TNS have been explored due to these uncertainties; however, current NICE guidelines do not recommend TNS use within the UK.
The authors suggest regulatory authorities should reconsider previous evidence supporting FDA clearance given these new findings.
