Researchers at King’s College London have determined that trigeminal nerve stimulation (TNS) does not reduce core symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. TNS is a non-invasive brain stimulation treatment previously cleared by the U.S. Food and Drug Administration (FDA) for ADHD in 2019. The findings were published in Nature Medicine and contradict the evidence that supported the FDA's initial clearance.
Study Details
The new study was a large, multi-center, double-blind, randomized controlled trial that included 150 participants. TNS operates by delivering a low electrical current via electrodes placed on the forehead, stimulating branches of the trigeminal nerve. The treatment is designed to activate brain regions involved in arousal and attention, which are often diminished in individuals with ADHD, offering an alternative to drug treatments.
FDA clearance for TNS in 2019 was based on a smaller U.S. pilot study involving 62 children. This earlier study reported improvements in ADHD symptoms after four weeks of nightly use and utilized a "sham" condition where participants wore electrodes but received no stimulation.
Senior author Katya Rubia, PhD, highlighted the importance of designing appropriate placebo conditions in clinical trials for brain therapies, citing a significant placebo effect observed with high-tech brain therapies. First author Aldo Conti, PhD, stated that the new multicenter trial aimed to address limitations of the previous pilot study, particularly through a rigorously controlled sham condition to ensure successful blinding. The trial also included adolescents, a group often in need of alternative ADHD treatments.
Methodology and Outcomes
Participants in the King's College London trial ranged from eight to 18 years old. Half received active TNS for approximately nine hours nightly over four weeks, while the other half received sham stimulation that delivered 30 seconds of low-frequency stimulation per hour, designed to mimic the sensation of active treatment without biological effect. ADHD symptoms were assessed using parent-rated scales, alongside measures of attention, hyperactivity, mood, sleep, mind-wandering, and objective physiological markers.
The data showed no significant difference between the real TNS group and the sham group on the primary outcome or almost all secondary outcomes. The device was found to be safe and well-tolerated, with no serious adverse events and similar side effect profiles in both groups. Both groups, however, demonstrated substantial improvement over the six months of the trial, with ADHD symptoms decreasing by 26% in the real TNS group and 29% in the sham group. Researchers attributed this to a pronounced placebo response, described as a "neurotechnology-induced placebo effect or ‘neuro-enchantment’."
One observed positive effect of TNS was a reduction in mind-wandering scores, though researchers cautioned this finding requires careful interpretation due to multiple comparisons and a lack of corroborating effects in older adolescents or objective attention measures.
Clinical Implications
The findings suggest that TNS should not be recommended as an effective treatment for ADHD, despite its safety profile. While TNS is approved for use in the U.S., it is not recommended in the U.K. by the National Institute for Health and Care Excellence (NICE). The King’s College team suggested that U.S. regulators may need to re-evaluate the original evidence supporting TNS approval.
Researchers plan to continue analyzing imaging data from the trial to understand why the proposed mechanisms of TNS did not produce clinical benefits and to inform the design of future studies on non-pharmacological interventions for ADHD.