Clinical Efficacy of Trigeminal Nerve Stimulation in Pediatric ADHD: A Double-Blind Randomized Controlled Trial

Abstract Trigeminal Nerve Stimulation (TNS) represents a promising non-pharmacological monotherapy for pediatric Attention-Deficit/Hyperactivity Disorder (ADHD), yet its efficacy and underlying neurobiological mechanisms remain intensely debated. Here, we present a randomized controlled trial (N = 218) evaluating active (120 Hz) versus active-control (2 Hz) TNS in ADHD. Although robust active-control responses attenuated differences on traditional continuous symptom scales, blinded clinician-rated Clinical Global Impression of Improvement scales revealed a 35% binary response rate in the active cohort compared to 15% in the control arm (OR = 3.07; 95% CI: 1.45–6.24; p = 0.002). Concurrent quantitative electroencephalography demonstrated that active TNS selectively modulates right frontal alpha power—an effect moderated by biological sex, emerging in boys but not in girls. These data validate the clinical efficacy of TNS, highlight the semi-active nature of low-frequency cranial nerve stimulation, and provide a sex-specific neurophysiological framework for targeted pediatric neuromodulation.