External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: External trigeminal nerve stimulation (TNS) received FDA clearance in 2019 as the first device-based, non-pharmacological treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), based on a small pilot sham-controlled randomized controlled trial (RCT) that reported symptom improvement in 62 children with ADHD. We conducted a confirmatory multi-centre, double-blind, randomized, sham-controlled, parallel-group, phase IIb RCT investigating short and longer-term efficacy (6 months) of real vs sham TNS in 150 children and adolescents with ADHD. Partricipants were randomized to receive real TNS ( n =75, mean age [ SD ]= 12.6 [2.8 years]), or sham TNS ( n =75, mean age [ SD ]= 12.6 [2.8 years]), nightly for 4 weeks. Bilateral stimulation targeted V1 trigeminal branches using battery-powered electrodes applied to the forehead for ~9 hours/night. Sham TNS delivered 30 seconds of stimulation per hour at a lower frequency. Intention to treat analysis (ITT) showed no significant differential treatment effects on ADHD symptoms (estimated adjusted mean difference [ aMD ] = 0.83; 95% Confidence interval [CI] = –2.47 to 4.13; p = 0.622; Cohen’s d = 0.09). No differential treatment effects were observed either on the secondary outcomes covering other symptom scales of ADHD and related clinical problems, as well as cognitive and physiological outcomes, except for a small reduction in mind wandering favouring real TNS ( aMD = –2.17; 95% CI = –4.33 to –0.01; p = 0.049; Cohen’s d = –0.27). Adherence was 94% and compliance 93%. Blinding was successful. No serious adverse events (SAEs) were reported, and side effects did not differ between groups. In conclusion, TNS is a safe intervention but does not demonstrate clinical efficacy for paediatric ADHD. Trial registration: ISRCTN82129325.
Source: Nature Medicine
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Granulosa Cell Tumor of the Ovary Foundation, South London and Maudsley NHS Foundation Trust, King's College Hospital NHS Foundation Trust, United Kingdom Clinical Research Collaboration, LifeArc, Solent NHS Trust, ACADIA Pharmaceuticals, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, Department of Health and Social Care, Nuffield Foundation, King's College London, European Commission, Rosetrees Trust, King's Health Partners, H. Lundbeck A/S, Medical Research Council, Research Executive Agency, Efficacy and Mechanism Evaluation Programme, St. George's, University of London, Programme Grants for Applied Research, Research for Patient Benefit Programme, Invention for Innovation, Health and Social Care Delivery Research, National Institute for Health Research Applied Research Collaboration South London
Awards: EPIGENETIC-GENETIC-MENTAL HEALTH CASCADE BASED PERSONALISED PREVENTION OF NON-COMMUNICABLE DISEASE IN ADOLESCENTS DIAGNOSED WITH AUTISM (ETHEREAL), A multi-centre, double-blind, parallel-group, randomized controlled study to compare the efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) on symptoms in youth with Attention Deficit/Hyperactivity Disorder (ADHD), Children of UPBEAT: a study of cardiovascular function in 10-year-old children of obese women who participated in an antenatal lifestyle intervention, G1830373972, Optimising community C(E)TRs through understanding the experience of people with intellectual disability and autistic people and investigating their impact on care, Stimulant Medication for ADHD and Tics - Understanding Response versus Non-stimulants (SATURN study): a randomised trial of the clinical and cost-effectiveness of methylphenidate versus guanfacine for ADHD in children and young people with a co-existing tic disorder, G2312300077, RECOGNeyes for Schools, Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients, G3412126590, Comparing pharmacological and non-pharmacological interventions for adults with Attention-Deficit/Hyperactivity Disorder (ADHD): systematic review and network meta-analysis, The DISCOVER implementation study: Investigating the sustainability and scale up of a schools based intervention to improve mental wellbeing of 16-18 years olds across six regions in England., Randomised trial of Haploidentical Transplantation compared to standard of care for Adults with Sickle Cell Disease, G434337789, Early intervention for depression and anxiety in 16-18 year olds : a multi-centre trial of self-referral psychological Stress workshop programmes in schools (BESST study - Brief Educational workshops in Secondary Schools Trial), A Randomised Double-Blind Placebo-Controlled Phase 3 Trial Of Triumeq In Amyotrophic Lateral Sclerosis, G4993504420, G5125246644, G5246421578, On-Line Parent Training for the Initial Management of ADHD referral (OPTIMA), A UK multi-centre cluster randomised control trial, with internal pilot, of the ADVANCE-Digitally supported perpetrator intervention compared to community justice offender management (1:1), to reduce intimate partner violence (IPV), for men convicted of IPV who misuse substances (ADVANCE-D trial), ADHD Remote Technology and ADHD transition: predicting and preventing negative outcomes (ART-transition), G589691944, CLEAR: (CLozapine in EARly psychosis) A Multi-Centre, Observational Study of Clozapine for Young People with Treatment Resistant Psychosis in Real World Settings, Personalising the pharmacological treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, Digital Sleep Support for Children with Attention-Deficit/Hyperactivity Disorder (The DISCA study), G7203804958, A PROspective double-blind placebo-controlled multicentre trial of faecal MIcrobiota tranSplantation to improve outcomEs in patients with cirrhosis - PROMISE trial., G860176508, Beta-blockers or placebo for primary prophylaxis of oesophageal varices (BOPPP study)
OpenAlex ID: W7124429023