New Study Casts Doubt on FDA-Cleared ADHD Device

A phase IIb trial in England suggested that a stimulation device cleared by the FDA in 2019 for children with attention-deficit/hyperactivity disorder (ADHD) may not be effective. In 150 children and adolescents, those treated nightly with the Monarch external trigeminal nerve stimulation (eTNS) system for 4 weeks had no significant differential treatment effects in ADHD-Rating Scale total scores compared with participants on sham TNS (estimated adjusted mean difference [aMD] 0.83, 95% CI -2.47 to 4.13, P=0.622, Cohen's d=0.09), reported Katya Rubia, PhD, of King's College London, and colleagues. Most secondary outcomes also didn't differ between groups except Mind Excessively Wandering Scale total scores at week 4, which significantly favored real TNS (aMD -2.17, 95% CI -4.33 to -0.01, P=0.049, Cohen's d=-0.27). "The findings of this large, double-blind, multicenter RCT [randomized controlled trial] do not provide support for TNS as an effective treatment for ADHD," Rubia and co-authors wrote in Nature Medicine. "If anything, the sham group had numerically reduced ADHD symptoms on the ADHD-Rating Scale at week 1 with an effect size of 0.3," they continued. "This conflicts with the positive findings from the previous pilot RCT of TNS in children with ADHD that showed an improvement in ADHD symptoms with medium effect size for real versus sham TNS with almost the same protocol with respect to trial duration (4 weeks) and dose/nightly settings." NeuroSigma's prescription-only eTNS system was the first non-pharmacological treatment cleared for ADHD in April 2019, based on data from a 62-participant clinical trial. The device is indicated for children ages 7-12 currently not taking prescription ADHD medication. The system works by delivering low-level electrical stimulation to branches of the trigeminal nerve, sending signals to parts of the brain thought to be involved in ADHD at night. Since its launch, over 1,000 Monarch eTNS systems have been dispensed in the U.S. While the FDA did not request more data, guidelines in the U.K. -- where the device is CE marked approved for use -- suggested more studies were needed before it could be recommended as an ADHD treatment, Rubia noted. "We felt a larger confirmatory trial is needed," she told MedPage Today. The FDA told MedPage Today it is currently reviewing the paper's findings. Rubia's team recruited participants in England from September 2022 to November 2024. Real TNS involved bilateral stimulation targeting the V1 trigeminal branches for 9 hours per night via battery-powered electrodes applied to the forehead. The sham intervention delivered 30 seconds of stimulation per hour at a lower frequency, followed by 3.57 seconds of no stimulation. This differed from the 2019 trial, which used a sham intervention that involved no stimulation at all. "Evidence shows that the placebo effect is greater in trials involving technology, such as neurofeedback and neurostimulation, as well as in studies with younger age groups, larger sample sizes, multisite designs, and higher baseline symptom severity," the researchers noted. "This is furthermore enhanced by a nocebo effect in those who realize that they are in the sham condition." The two trials had other differences, Rubia and co-authors acknowledged, pointing out that "we included long-term medicated children (39.3%) and a larger age range of children and adolescents of 8-18 years, whereas the previous study was restricted to non-medicated children (8-12 years)." The mean age in the current trial was 12.6 years. The most commonly reported adverse device effects were headaches (21.3% in the real TNS group vs 17.3% in the sham group) and difficulties falling asleep or sleep disturbances (20% vs 9.3%). "No serious adverse events were reported, and side effects did not differ between groups," Rubia and colleagues wrote. There was a high rate of missing data from teacher ratings, which limited the ability to measure behavioral changes in school settings, the researchers noted.