biostudies-literatureConti AANational Institute for Health Research (NIHR)DH | NIHR | Efficacy and Mechanism Evaluation Programme (NIHR Efficacy and Mechanism Evaluation Programme)582-590https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920111biostudies-literatureUnknown32(2)External trigeminal nerve stimulation (TNS) received US Food and Drug Administration 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. Here we conducted a confirmatory multicenter, double-blind, randomized, sham-controlled, parallel-group, phase 2b RCT to investigate short-term and long-term efficacy (6 months) of real versus sham TNS in 150 children and adolescents with ADHD. Participants were randomized to receive real TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) or sham TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) nightly for approximately 9 hours for 4 weeks. Bilateral sNature medicineExternal trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial.PMC1292011117/32/04RP-PG-0618-20003NIHR203684NIHR203035NIHR158490NIHR127921NIHR127951NIHR207448NIHR128472NIHR165421NIHR130674NIHR130730NIHR154546NIHR303122NIHR130077NIHR131175Mehta MAConti AABilbow AHyde JGiaroli GCarter BEl Masri SMarhenke RSantosh PStringer DLiang HCortese SBozhilova NFiori FJohansson LRubia KEraydin IEfalseExternal trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial.External trigeminal nerve stimulation (TNS) received US Food and Drug Administration 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. Here we conducted a confirmatory multicenter, double-blind, randomized, sham-controlled, parallel-group, phase 2b RCT to investigate short-term and long-term efficacy (6 months) of real versus sham TNS in 150 children and adolescents with ADHD. Participants were randomized to receive real TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) or sham TNS (n = 75, mean age (s.d.) = 12.6 (2.8) years) nightly for approximately 9 hours for 4 weeks. Bilateral s2026-01-01T00:00:00Z2026 Feb2026-07-16T12:33:59.316Z2026-07-09T10:55:39.799ZS-EPMC129201114154558710.1038/s41591-025-04075-x