Large Trial Reveals Brain Stimulation Offers No Benefit for ADHD

For families seeking alternatives to attention-deficit/hyperactivity disorder (ADHD) medication, brain stimulation has been promoted as a promising option. However, a new multicenter trial led by King’s College London shows that trigeminal nerve stimulation (TNS) does not improve ADHD symptoms in children and adolescents. The study found no meaningful differences between real and sham treatment (placebo). Why stimulate the brain to treat ADHD—and why test it again? ADHD affects ~5–8% of children worldwide. For many, symptoms persist into adolescence and adulthood, shaping their education, relationships, and mental health. Stimulant medications remain the main treatment and work well for many people in the short term; however, they can have limitation. Side effects are common, long-term benefits are uncertain, and adherence often drops during adolescence. These issues have fuelled interest in alternatives that do not involve medication. One area that has attracted attention is non-invasive brain stimulation, often grouped under the broad label of neuromodulation. The idea is to use mild electrical signals to influence brain systems linked to attention and behaviour. TNS is one popular approach. It delivers small electrical pulses through electrodes placed on the forehead, targeting branches of the trigeminal nerve. These signals are thought to reach deep brain areas involved in alertness and attention. Interest in TNS grew after a small US study of 62 children reported reduced ADHD symptoms after 4 weeks of nightly stimulation, subsequently leading to the approval of TNS by the US Food and Drug Administration (FDA) in 2019, as the first non-pharmacological treatment for ADHD. However, the evidence base was thin. The control group received no stimulation at all, making it hard to separate real effects from expectations, and blinding was also not properly tested. In addition, “the pilot study did not assess effects beyond 4 weeks and was limited to very young children aged 8−12 years,” noted the authors of the latest study. In the UK, these uncertainties meant that TNS was never recommended by the National Institute for Health and Care Excellence (NICE), with their guidelines stating: “Evidence on the safety and efficacy of transcutaneous electrical stimulation of the trigeminal nerve for ADHD is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research.” What was missing was a large, independent trial with a strong placebo control. “This multicentre trial was designed to address key limitations of the previous pilot study that informed FDA clearance of TNS for ADHD, particularly by using a rigorously controlled sham condition that supported successful blinding across the treatment period,” explained first author Dr. Aldo Conti, a postdoctoral research associate at the Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care at King’s College London. The trial’s goal was to deliver a clearer answer on whether TNS truly helps children and adolescents with ADHD. Testing brain stimulation for ADHD in a larger controlled trial Conti and the team ran a multicentre randomized controlled trial involving 150 children and adolescents aged 8–18 years with ADHD. Advertisement “Unlike the earlier study, which was limited to younger children, we also included adolescents, a clinically important group given well-documented challenges with long-term medication adherence,” said Conti. Participants were randomly assigned to receive either active TNS or a sham version designed to act as a believable placebo. Both groups used the same device at home for around nine hours each night over four weeks. The active group received continuous therapeutic pulses, whereas the sham group received brief, low-intensity stimulation that was unlikely to have a biological effect but helped maintain blinding. ADHD symptoms were reported weekly by parents using standard rating scales. The researchers also measured attention and activity using tasks and wearable devices, alongside mood, anxiety, sleep, and mind-wandering. Although ADHD symptoms improved in both groups, there was no meaningful difference between real and sham stimulation. The same pattern held for objective measures of attention and hyperactivity, as well as mood and sleep. Both groups showed substantial symptom improvement, consistent with a strong placebo response that the authors note is often larger in trials involving high-tech brain stimulation devices. “TNS is a safe intervention but does not demonstrate clinical efficacy for pediatric ADHD,” summarized the team. Participants, parents, and researchers were largely unable to guess treatment assignment, suggesting blinding was successful throughout the trial. What this means for ADHD treatment and brain stimulation research The findings suggest that TNS does not offer benefits beyond placebo for children and adolescents with ADHD, at least when used in this way and for this duration. That conclusion challenges the evidence that supported FDA clearance. Advertisement “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,” said corresponding author Dr. Katya Rubia, a professor of cognitive neuroscience at the Institute of Psychiatry, Psychology & Neuroscience at King's College London. Without careful trial design, these expectations can easily be mistaken for treatment effects. “Rigorous evidence, such as that generated by this study, is essential for supporting shared decision-making regarding interventions for ADHD,” said co-senior author Dr. Samuele Cortese, a professor of child and adolescent psychiatry at the University of Southampton. “Clinicians, individuals with ADHD, and their families need to know which treatments work, and which do not, based on the best evidence.” The intervention only lasted four weeks, and longer treatment periods were not tested. Different stimulation settings or patient groups might produce different results; however, the absence of any early signal makes strong claims of benefit hard to justify. Devices cleared on small, weakly controlled studies may need closer scrutiny as better data become available, the researchers suggest, and future work should prioritize treatments supported by stronger evidence and more clearly defined biological mechanisms. Reference: Conti AA, Bozhilova N, Eraydin IE, et al. External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial. Nat Med. 2026. doi: 10.1038/s41591-025-04075-x