The Food and Drug Administration (FDA) has approved a non-medication treatment for children with Attention Deficit / Hyperactivity Disorder who are not currently medicated.
The external trigeminal nerve stimulation system (eTNS) device, approved in 2019, sends low-level electrical pulses to the brain while the children sleep.
A clinical trial of the device found the results of the treatment were similar to those achieved with non-stimulant medication.
The prescription-only device, called the Monarch external Trigeminal Nerve Stimulation (eTNS) System, is indicated for patients ages 7 to 12 years old who are not currently taking prescription ADHD medication.
It is the first non-drug treatment for ADHD granted marketing authorization by the FDA.
“This new device offers a safe, non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind,” said Carlos Peña, Ph.D., director of the Division of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health.
The Monarch eTNS System is intended to be used in the home under the supervision of a caregiver.
The cell-phone sized device generates a low-level electrical pulse and connects via a wire to a small patch that adheres to a patient’s forehead, just above the eyebrows, and should feel like a tingling sensation on the skin.
The system delivers low-level electrical stimulation to the branches of the trigeminal nerve, which sends therapeutic signals to the parts of the brain thought to be involved in ADHD.
While the exact mechanism of eTNS is not yet known, neuroimaging studies have shown that eTNS increases activity in the brain regions that are known to be important in regulating attention, emotion and behavior.
The stimulation should feel like a tingling sensation on the skin, and the device should be used in the home under the supervision of a caregiver during periods of sleep.
Clinical trials suggest that a response to eTNS may take up to 4 weeks to become evident. Patients should consult with their health care professional after four weeks of use to assess treatment effects.
The Monarch eTNS System’s efficacy in treating ADHD was shown in a clinical trial that compared eTNS as the sole treatment, or monotherapy, to a placebo device.
A total of 62 children with moderate to severe ADHD were enrolled in the trial and used either the eTNS therapy each night or a placebo device at home for four weeks. The trial’s primary endpoint was improvement on a clinician-administered ADHD Rating Scale, which is used to monitor severity and frequency of ADHD symptoms. A higher score is indicative of worsening symptoms.
The ADHD-RS uses questions about the patient’s behavior, such as whether they have difficulty paying attention or regularly interrupt others. The trial showed that subjects using the eTNS device had statistically significant improvement in their ADHD symptoms compared with the placebo group. At the end of week four, the average ADHD-RS score in the active group decreased from 34.1 points at baseline to 23.4 points, versus a decrease from 33.7 to 27.5 points in the placebo group.
The most common side effects observed with eTNS use are: drowsiness, an increase in appetite, trouble sleeping, teeth clenching, headache and fatigue. No serious adverse events were associated with use of the device.
The Monarch eTNS System should not be used in children under seven years of age. It should not be used in patients with an active implantable pacemaker or with active implantable neurostimulators. Patients with body-worn devices such as insulin pumps should not use this device.
The eTNS System should not be used in the presence of radio frequency energy such as magnetic resonance imaging (MRI), because it has not been tested in an MRI machine, or cell phones, because the phone’s low levels of electromagnetic energy may interrupt the therapy.
The FDA granted marketing authorization of the Monarch eTNS System to NeuroSigma.
In October 2020, the NeuroSigma firm, based in Los Angeles, published updated findings on the efficacy of its device in the Journal of the American Academy of Child & Adolescent Psychiatry in a paper entitled Trigeminal Nerve Stimulation for Attention-Deficit Hyperactivity Disorder: Cognitive and Electrophysiological Predictors of Treatment Response.
The objective of the research, led by Sandra Loo, Ph.D., Professor of Psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior, was to explore the applicability of a precision medicine approach to Trigeminal Nerve Stimulation by testing secondary outcomes of cognitive and electrophysiological (EEG) predictors of treatment response among subjects from the original randomized controlled trial.
The research demonstrated that certain baseline characteristics such as lower working memory performance, deficits on the behavioral ratings of executive functions (BRIEF) scale, and lower resting state EEG power in the right frontal brain region were predictive of positive treatment response to eTNS (p < 0.05). Further, upon completion of the four week eTNS treatment regimen, responders had significantly higher power in right frontal EEG readings, which was significantly correlated with improvement in executive function and ADHD symptoms.
“Our work with eTNS suggests that successful treatment response to eTNS appears to address a number of cognitive and neural deficits typically associated with ADHD,” said Dr. Loo. “Additional investigations of this new treatment modality are warranted to better understand these effects, to predict which children may benefit prior to initiating treatment, and to provide independent replication in larger samples of children with ADHD,” she added.
In the European Union, the Monarch eTNS System is approved as adjunctive therapy for drug resistant epilepsy and major depressive disorder, as well as monotherapy for ADHD, all in patients 7 years and older.
The trigeminal nerve is the largest cranial nerve, offering a high-bandwidth pathway for signals to enter the brain, bilaterally and at high frequency. The trigeminal nerve projects directly or indirectly to specific areas of the brain, such as the locus coeruleus, nucleus tractus solitarius, thalamus, and the cerebral cortex, which are involved in attention-deficit hyperactivity disorder (ADHD) and other disorders.
Trigeminal Nerve Stimulation (TNS) is mild electrical stimulation of branches of the trigeminal nerve, including those located near the surface of the forehead. Functional neuroimaging data suggests the mechanism of action of TNS is related to its ability to modulate activity in targeted brain regions.