# External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trial

## TL;DR

A study of 150 children found that a non-drug treatment for ADHD called TNS was safe but did not significantly improve symptoms compared to a placebo.

## Contribution

The first large, confirmatory trial of TNS for ADHD in youth, evaluating both short-term and long-term efficacy.

## Key findings

- TNS did not show significant improvement in ADHD symptoms compared to sham treatment.
- The treatment was found to be safe with no serious adverse events reported.
- Side effects were similar between the real and sham TNS groups.

## Abstract

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 stimulation targeted V1 trigeminal branches using battery-powered electrodes applied to the forehead. Sham TNS delivered 30 seconds of stimulation per hour at lower frequency and pulse width. Intention-to-treat analysis showed no significant differential treatment effects on ADHD symptoms (primary outcome) (estimated adjusted mean difference = 0.83; 95% confidence interval: –2.47 to 4.13; P = 0.622; Cohen’s d = 0.09). No serious adverse events were reported, and side effects did not differ between groups. In conclusion, TNS is a safe intervention but does not demonstrate clinical efficacy for pediatric ADHD. Trial registration: ISRCTN82129325.

A large, multicenter, double-blind RCT in 150 children and adolescents found that external trigeminal nerve stimulation, although safe and well tolerated, did not produce significant short-term or long-term clinical benefits for ADHD compared to sham treatment.